标签归档 夜上海

　　On the morning of June 22nd, the roof of the foundation pit was finally poured on the southeast side of the intersection of G40 Hushan Expressway and Jin ‘an Road in Changxing Island, Chongming, Shanghai, which marked the successful capping of the main structural project of the 108-size shield transfer section of Chongming Line of Shanghai rail transit and became the first unit project of Shanghai Chongming Line.

　　Shanghai Chongming Line will cross the Yangtze River twice in the form of full underground for the first time, and the foundation pit of the 108-standard shield transfer section will be constructed by open excavation method, which is arranged in the north-south direction and is a single-column double-span concrete box structure with two floors above the ground and four floors underground (partially underground).

　　As a large-diameter slurry-water balanced shield tunnel with the longest one-time tunneling distance in domestic rail transit, the two large and small shield conversion sections at Bid 108 and Bid 111 on Changxing Island will be the most important conversion points between Chongming Line’s single-hole double-line oversize shield and Changxing Island Station’s double-hole double-line small shield, and it is also one of the most important and difficult engineering nodes to realize crossing the Yangtze River.

　　After the resumption of project construction, the main structure of the 108-bid project was successfully capped, which created favorable conditions for the subsequent success of the 13-meter super-large shield crossing the Yangtze River and the promotion of the construction of the entire Chongming Line.

　　Since the beginning of May, the construction units of Shanghai rail transit have strictly followed the epidemic prevention requirements and made every effort to catch up with the progress of the project construction. At present, eight major projects, such as shanghai metro line 13 West Extension, Line 17 West Extension, Line 18 Phase II and Chongming Line, have reached production on June 20, and all 59 work sites involved in the whole network will reach production by the end of June.

　　(CCTV reporter Sheng Yuyu Shi Chenyang)

What is Bioaccumulation?

What do you get when you decompose the term "bioaccumulation"? The word accumulation meansSomethingThe accumulation of, and the prefix bio- meanlife. Put it together, it is.Something accumulates in living things.To defineBioaccumulation.

Then biological accumulation is used to refer toChemical substances in organismsThe accumulation of. These substancesCann’t be metabolized , it accumulates in organisms and accumulates through the food habits of consumers at all levels in the food chain.The higher the level, the higher the cumulative concentration in the body of consumers.The phenomenon.

How does bioaccumulation occur?

One way is to let a certain amount of chemicals enter the organism.Faster thanThe rate at which organisms decompose and use it. This means that more chemicals enter than are discharged, leading to the accumulation of chemicals in organisms.

Another main way is that chemicals enter organisms, and organismsIt cannot be decomposed or excreted in some way.. So chemicals will continue to accumulate,Until it eventually becomes fatal to organisms..

All organismsThe problems we face are allThe result of dynamic balance between absorption and elimination. biological accumulationThe degree of occurrence determines the toxic effect.. In some cases, the protection mechanism is protected from certain undesirable substances deposited in special parts to prevent them.Participate in metabolic reaction.

The bioaccumulation description in this paper is used to evaluate the accumulation of drugs and their harmful metabolites in intestinal bacteria.

Therapeutic drugs will have a strong impact on intestinal microflora, and vice versa.Potential drug-bacterial interactions can be mediated by biologicalTransformation reduces microbial adaptability or changes drug availability.. The latter can have a positive or negative impact on drug activity and efficacy. Although drugs such as lovastatin and sulfasalazine will be chemically affected by intestinal bacteria.Convert into active formBut bacterial metabolism can make digoxin and so on.Drug inactivation, or like irinotecan (irinotecan).toxic effect. In order to further increase the diversity of susceptible drugs, it was recently reported that more than 100 molecules were chemically modified by intestinal bacteria.However, the mechanism of these interactions is mainly limited to drug biotransformation..

Lovastatin (lovastatin)

Lovastatin can reduce the synthesis of cholesterol and increase the synthesis of low-density lipoprotein receptor, mainly in the liver, resulting in the reduction of blood cholesterol and low-density lipoprotein cholesterol levels, thus playing a role in the prevention and treatment of atherosclerosis and coronary heart disease (source: Baidu Encyclopedia).

Sulfasalazine (sulfasalazine)

Sulfasalazine (sulfanilamide) is an antibacterial agent. It is a sulfonamide which is not easily absorbed by oral administration. The absorbed part is decomposed into 5-aminosalicylic acid and sulfapyridine under the action of intestinal microorganisms. 5-aminosalicylic acid stays in the intestinal wall tissue for a long time after complexing with the intestinal wall connective tissue, which plays an antibacterial, anti-inflammatory and immunosuppressive role, such as reducing Escherichia coli and Clostridium, and inhibiting the synthesis of prostaglandin and leukotrienes (source: Baidu Encyclopedia).

Digoxin

Digoxin is an intermediate cardiac glycoside, which is white crystal or crystalline powder. Odorless; It tastes bitter. In the treatment, the effect on the heart is positive inotropic effect, slowing down the heart rate and inhibiting heart conduction. It is suitable for congestive heart failure with low output, atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia.

Bacteria in the intestine can regulate the availability and efficacy of therapeutic drugs. However, the potential mechanism of the interaction between drugs and bacteria is the chemical transformation or biological transformation of drugs by microorganisms.

A team of scientists from Heidelberg, Germany and Cambridge, England just published in Nature, and successfully studied the consumption of 15 drugs with different structures by 25 representative intestinal bacterial strains. 70 kinds of bacteria and drug interactions were revealed, 29 of which were not reported before. More than half of the new interactions can be attributed to biological accumulation.

This biological accumulation of intestinal bacteria may be a common mechanism to change drug availability and bacterial metabolism, which may have little effect on individuals.Biota composition, pharmacokinetics, side effects and drug reactionsHave an impact.

01

Drug non-metabolic accumulation

For a more detailed investigationDrugs and bacteriaA systematic map of the interaction between scientists.Two analytical methodsNuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) were used to systematically analyze 1.Five human targeted drugs and 25 human intestinal bacteria.Interaction between Bifidobacterium longum, Escherichia coli and other subspecies or strains of the same species of Bacteroides Homogeneous. Select bacterial species to cover those representing healthy microbial communities.Extensive phylogeny and metabolic diversity. In terms of drugs, 12 kinds of oral small molecular drugs (molecular weight less than 500 Da) were selected, which can be quantified based on ultra-high performance liquid chromatography combined with ultraviolet detection (UPLC-UV) toCross different chemical, indication areas and side effects.

Bacterial-drug interaction network. Left network: biotransformation or accumulation of drugs by intestinal bacteria. Right network: the influence of drugs detected in at least two independent screening on the growth of intestinal bacteria (Student’s t test, α = 0.05). The full names of bacteria not mentioned in this paper are as follows: Bacteroides fragilis, Bacteroides vulgaris and Bifidobacterium animalis subspecies. Lactobacillus BI-07, Coprococcus come, Clostridium, Clostridium, lactobacillus paracasei, Ruminococcus gnavus.

Among the 29 newly discovered interactions (14 drugs and 4 drugs), as many as 17 species are bioaccumulation events.; That is to say,Drugs are stored by bacteria without changing it.. the rest Twelve interactions (8 drugs and 5 drugs) may represent biotransformation events.. Two of the five drugs: levamisole and ezetimibe, were indeedOther intestinal bacterial chemistry coursesDecorate.

Among bioaccumulative drugs,Antidepressant Duloxetine/Cymbalta(duloxetine) andRosiglitazone, a hypoglycemic drug.beThe only bioaccumulative drugEach species accumulates in many different species.

However, biodegradation and bioaccumulationInteraction is not mutually exclusive.. Montelukast (for asthma) and roflumilast (for chronic obstructive pulmonary disease)Bioaccumulation by some bacteria and degradation by other bacteria.. In terms of bacteria, all strains except Fusobacterium nucleatum showed two types of interactions. In addition to the interaction with widely interacting control drugs sulfasalazine and metronidazole, the same strains of Bifidobacterium (B. uniformis) and Escherichia coli (E. coli) were found to be in the same strain.There is no overlap in interaction.. Because individuals usually have different strains, bioaccumulation is interactive.The prevalence rate may be higher than the research results..

Levamisole (levamisole)Levamisole is a broad-spectrum anthelmintic drug, which is mainly used to repel ascaris and hookworms. It can improve the resistance of patients to bacterial and viral infections. At present, it is used as adjuvant therapy for lung cancer and breast cancer after surgery or acute leukemia and malignant lymphoma after chemotherapy.

Ezetimibe (ezetimibe)Selective cholesterol absorption inhibitor is a lipid-lowering drug.

Duloxetine/Simpatine, mainly used to treat depression. It mainly regulates the balance of neurochemicals in brain tonic by inhibiting the recovery of serotonin and norepinephrine.

Rosiglitazone (rosiglitazone)Rosiglitazone and pioglitazone are thiazolidinedione hypoglycemic agents commonly used in clinical treatment in China at present. This product is an insulin sensitizer. By increasing the sensitivity of skeletal muscle, liver and adipose tissue to insulin and improving the utilization of glucose by cells, it can significantly reduce fasting blood glucose, insulin and C-peptide levels, and also reduce postprandial blood glucose and insulin. However, patients are required to have a certain ability to secrete insulin.

The World Health Organization’s International Agency for Research on Cancer listed rosiglitazone in the list of three carcinogens.

Due to manyHuman targeted drugs have been proved to affect the growth of intestinal bacteria.. The study examined the identifiedCan bacterial-drug interactions also lead to growth changes?. Although more than 30 major inhibitory drug-bacteria interactions have been detected, only.The three kinds of interactions involve both modifying growth and changing drug concentration.(excluding control drugs sulfasalazine and metronidazole). Therefore,The interaction between bacteria-drugs and drugs-bacteria seems to be largely independent..

In order to confirm the bioaccumulation of the interaction between bacteria and drugs, the study usedThe other two analytical methods are nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS).. As a case in point,Duloxetine, a widely used antidepressant, was found to be bioaccumulated by eight kinds of bacteria. Nuclear magnetic resonance spectroscopy can clearly detect duloxetine and confirm it.Four selected strains(Streptococcus salivarius, Bacteroides simplex, Escherichia coli IAI1 and Escherichia coli ED1a) were removed from the culture medium without biotransformation. LC-MS analysis in compound GMM medium also confirmed it.Clostridium saccharides and Escherichia coliBioaccumulation of IAI1 in the concentration range of 30 to 70.

Nuclear magnetic resonance analysis showed that Streptococcus salivarius was sensitive to duloxetine.biotic pyramid

02

Biological accumulation affects cell metabolism.

Although biotransformation can be attributed tometabolic enzymeHowever, drug bioaccumulation is in mechanism.It’s even harder to imagine. In order to study the molecular basis of drug bioaccumulation by intestinal bacteria, scientists set out to determine the concentration of duloxetine in bioaccumulative strains.Protein target. Firstly, an acetylized, "clickable" molecular version was constructed and used as bait.　　

Click chemistry and thermal protein group analysis (TPP) showed that protein binding was a contributing factor to duloxetine bioaccumulation. This raises the question of whyThese two strains of E.coli showed different degrees of duloxetine bioaccumulation in GMM.. Two strains of Escherichia coli were compared in two different TPP assays, in which drugs were added to lysed cells or whole cells. Although TPP in cell lysate can find protein which is stable or unstable due to the direct binding of duloxetine, intact cell TPP can also capture the changes of cell reaction (changes of protein interaction and activity) in vivo.

Note: Click Chemistry, which aims to create various functional substances (candidate drug compounds, biological probes, soft materials, etc.), is a very widely used reaction. As a basic technology, it is characterized by high chemical selectivity, high yield, fast reaction speed and easy formation of strong chemical bonds.

In a complete cell assay,biotic pyramidThe IAI1 strain is more abundant than the abiotic ED1a strain.Has almost twice as muchDrug-reactive protein, and thermostable.The overall change is stronger. Consistent with the fact that duloxetine changed cell physiology more significantly in bioaccumulative strains, IAI1 strain also showed it in differentially expressed protein.A more obvious reaction.

In contrast, these two strains show very similar characteristics in TPP based on lysate, in which the lack of cell envelope enables drugs to reach all intracellular protein. Therefore,The strain specificity of bioaccumulation is probably due to the difference of absorption and consumption systems, which is similar to the transporter-dependent specificity observed in drug-drug interaction..

The combination of duloxetine and metabolic enzymes shows that the biological accumulatorMetabolism has changed.. To test this, two complementary metabolomics platforms were used-Flow injection analysis mass spectrometry (FIA-MS) and hydrophilic interaction chromatography combined with tandem mass spectrometry (HILIC-MS/MS).Methods: To analyze the effects of duloxetine treatment on six bacterial strains (four bioaccumulative and two non-bioaccumulative)Small molecule secretion.

Among the four strains, there are three bioaccumulative types (C. saccharolyticum, Lactobacillus plantarum and E.coli IAI1) and one non-bioaccumulative type (Lactococcus lactis), which show their characteristics after drug treatment in GMM.A significant shift in metabonomic patterns. The drug-induced changes in the ectometabolism group are equivalent to the interspecific differences.　

In addition, the drug reaction was concentration-dependent, and no effect was observed on the non-bioaccumulated roflumilast. The concentration-dependent reaction to duloxetine was further verified by a subset of 71 metabolites, in which the chemical characteristics were presumed to be assigned-two metabolites confirmed by chemical standards-using tandem mass spectrometry. Clostridium saccharolyticum also showed a strong metabolic response to duloxetine when detected in nutrient-deficient PBS buffer.

Anyway,Protein omics and metabonomics data show that duloxetine binds to abundant metabolic enzymes to support its intracellular storage..

three

Biological accumulation leads to cross-feeding

Metabolic interaction is the basis of shaping the composition of intestinal microbial community.. So, will the metabolic changes related to biological accumulation affect the community composition?

In order to solve this problem, the researchers assembled five stable communities of intestinal bacterial species (Bacteroides thetaiotaomicron, Eubacterium rectale, Lactobacillus gasseri, Ruminococcus bolts, Streptococcus salivarius) with and without duloxetine. One of these five species is S. salivarius, and the other is directly inhibited by E. rectale. These five species were co-inoculated in GMM and then transferred to fresh medium every 48 hours.　

The existence of duloxetine significantly changed the community composition.Compared with the situation without drugs,The abundance of E.coli in rectum has increased by more than 100 times.. This is noteworthy because of the five species used by researchers,Rectal Escherichia coli is the most sensitive to duloxetine.. Consistent with Streptococcus salivarius as a bioaccumulator, duloxetine is exhausted in the supernatant of the community. Although decreasing the concentration of duloxetine can protect the rectal Escherichia coli in the community, it takes longer to reproduce in the presence of duloxetine.

Duloxetine bioaccumulation changes community assembly and host response.

supposesalivaChanges in the secretion of duloxetine metabolites by Streptococcus liquidus can promote rectal Escherichia coli.. Supporting this, the used culture medium from S. salivarius grown in the presence of drugs improved the growth of E. rectale. Non-targeted metabolomics data from FIA-MS and HILIC-MS/MS further support the cross-feeding hypothesis.　

Therefore, it was found that several metabolites were accumulated in the culture process of S. salivarius and then exhausted in the growth process of E. rectale. Among them, five metabolites are presumed to be annotated,Linolenic acid and cholic acidIt is confirmed by using analytical standards (methods). The changes of nucleotide-related metabolites (such as uridine -5′- diphosphate) are consistent with the critical nature of protein and metabolites influenced by duloxetine and E. rectale. Therefore,Human targeted drugs can regulate intestinal microbial community, not only by direct inhibition, but also by creating cross-feeding opportunities..

04

Bioaccumulation affects host response.

Then, the researchers used Caenorhabditis elegans as a model system to study the effect of duloxetine bioaccumulation on host response. Duloxetine as a kind ofSerotonin-norepinephrine reuptake inhibitorAnd regulate the behavior (muscle movement) of Caenorhabditis elegans in a concentration-dependent manner.　

In the presence of bioaccumulative species (Escherichia coli IAI1) as part of the growth medium of Caenorhabditis elegans, animal movements were examined as behavioral readings. As a closely related control, the researchers used E.coli ED1a strain which did not bioaccumulate in complex growth medium. In fact,Only strain IAI1, a bioaccumulation strain of duloxetine, weakened the influence of duloxetine on the host.Although the intestine of C. elegans is colonized by facultative anaerobic bacteria and obligate aerobic bacteria, it is likely to be aerobic, but the results are very consistent with the biological accumulation observed in anaerobic culture experiments.

Therefore, it is necessary to further study the microbiome-duloxetine-host interaction in other model systems or clinical environments.

05

Total knot

The results reveal that the therapeutic effect of host-targeted drugs can be achieved by intestinal bacteria in two ways.biotic pyramidTo adjust:

First, the main effect produced by reducing the availability of drugs;

Second, the secondary effect produced by changing the secretion of metabolites.　

The latter willLead to changes in community composition.This is related to some drugsassistantAction and even the mode of action.. For the case drug duloxetine in this study, the intestinal bacterial interaction is indeed related to the side effects such as weight gain and its mode of action.

editorial comment/note

Bacteria in the intestine can affect the activity or efficacy of drugs. Recent studies show that this effect is not only biotransformation (changing the composition of drugs or metabolizing them into new substances),Bioaccumulation of drugs stored in cells by specific bacteriaIt may be another important influence (accounting for more than half of the newly discovered role). By accumulating drugs in cells, it willGreatly changes the efficacy of many dose-dependent drugs.(such as the antidepressant duloxetine under study), and it absorbs the bacteria that have accumulated drugs.Metabolism will change., which in turn willaffectInteracting with itOther bacteriaAnd finally change the composition of the flora.

References:

Klünemann M, Andrejev S, Blasche S, Mateus A, Phapale P, Devendran S, Vappiani J, Simon B, Scott TA, Kafkia E, Konstantinidis D, Zirngibl K, Mastrorilli E, Banzhaf M, Mackmull MT, H?velmann F, Nesme L, Brochado AR, Maier L, Bock T, Periwal V, Kumar M, Kim Y, Tramontano M, Schultz C, Beck M, Hennig J, Zimmermann M, Sévin DC, Cabreiro F, Savitski MM, Bork P, Typas A, Patil KR. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature. 2021 Sep 8. doi: 10.1038/s41586-021-03891-8. Epub ahead of print. PMID: 34497420.

The patent dispute was once again staged between Xiaomi Group and Huawei. On December 12, Xiaomi Group issued a statement saying that recently,Mr. Yu Chengdong made false statements against the company’s "keel shaft" technology for no reason, which was seriously inconsistent with the facts.

The dispute stems from the speech made by Yu Chengdong, managing director of Huawei, CEO of terminal BG and chairman of BU, a smart car solution, at the Huawei Pollen Annual Meeting in 2023: "Don’t respect us very much.(Huawei)Intellectual property rights, take it and just make up a name and say your own. Double-rotating water drop hinge directly becomes keel hinge, and keel does not exist. "　

It is worth noting that both the "double-rotating water drop hinge" and the "keel hinge" are the key components of the folding screen mobile phone, which is the key to determine the completion of the folding screen mobile phone product. In the context of sluggish demand in the terminal market, the "dark horse" of folding screen mobile phones has a considerable market in the future. Moving towards folding screens has become a tacit strategic direction for mobile phone manufacturers.

First, Xiaomi Group publicly clarified

At noon on December 12th, the reporter of national business daily learned from Xiaomi Group that the spokesman of Xiaomi Company released a clarification message through Weibo, saying that recently, Mr. Yu Chengdong made false remarks against the company’s "keel shaft" technology for no reason, which was seriously inconsistent with the facts. Please ask Mr. Yu Chengdong to follow the basic rules of "science and rigor" and stop discrediting his peers and misleading the public.

Image source: Sina Weibo

This "war" originated from the speech made by Yu Chengdong, managing director of Huawei, CEO of BG and chairman of BU, a smart car solution, at the 2023 annual pollen conference. At that time, he once "bombarded" friends and merchants for plagiarism: "Don’t respect us very much.(Huawei)Intellectual property rights, take it and just make up a name and say your own. Double-rotating water drop hinge directly becomes keel hinge, and keel does not exist. "　

This remark attracted Xiaomi’s "return".

According to Xiaomi Group, the "keel shaft" is a new generation of folding shaft developed by Xiaomi Group, and it is the first three-level rod group structure in the industry. No matter the design idea or the mechanical structure, the "keel shaft" is completely different from the "double-rotating water drop hinge" declared by Mr. Yu Chengdong.

Xiaomi said that after studying the technical information and published patent information disseminated by Mr. Yu Chengdong’s company, and after actual disassembly and verification, the "double-rotating water drop hinge" adopts the design scheme of "2-level rod group, 3 components and 4 low pairs"; The mechanical structure of Xiaomi’s self-developed "keel shaft" adopts the innovative design of "3-level rod group, 5 components and 7 low pairs".

At the same time, Xiaomi also took a number of screenshots in the social media comment area, saying that the company’s self-developed "keel shaft" applied for a patent on September 18, 2020 and was granted a patent on January 5, 2021; August, 2023 in Xiaomi MIX Fold.(Mobile phone model)On the first application. The "double-rotating water drop hinge" claimed by Mr. Yu Chengdong applied for a patent on December 13th, 2019 and was published on June 18th, 2021. Yu Chengdong’s company’s patent application for the three-level bar group was filed on October 29th, 2021 and made public on May 5th, 2023. So far, there is no information to confirm the authorization, and it has not been commercialized.

Judging from the attitude of Xiaomi Group, this response can be described as sharp: "Please ask Mr. Yu Chengdong to follow the basic rules of’ science and rigor’, and don’t discredit his peers and mislead the public."

As of press time, Huawei has not responded to the above statement of Xiaomi Group.

Second, the patent dispute between the two parties is not the first time.

In the face of this "Mihua patent dispute", many netizens expressed their opinions in the comment area.

National business daily reporter noticed that many netizens talked about the different types of patents involved in Xiaomi and Huawei. According to the information disclosed by Xiaomi, the patent type of the company’s "hinge, display module and terminal equipment" is "utility model"; Huawei’s patent type of "folding mechanism and folding electronic equipment" is "invention application".

Some netizens’ opinions Image source: social media screenshot　

However, some netizens pointed out that,Xiaomi’s patent for "hinge, display module and terminal equipment" also involves "double application in one case" when applying.

According to the analysis of a person in the industry who did not want to be named, the above case of Xiaomi may involve "double application in one case". Paragraph 1 of Article 9 of the current Patent Law stipulates: "Only one patent right can be granted for the same invention-creation. However, if the same applicant applies for both a patent for utility model and an invention patent for the same invention-creation on the same day, and the patent right for utility model obtained first has not been terminated, and the applicant declares to give up the patent right for utility model, the invention patent right may be granted. "

According to public information, the "keel hinge" technology is used on Xiaomi’s flagship folding screen mobile phone Xiaomi MIX Fold 3 released this year. Lei Jun, chairman of Xiaomi, once said that Xiaomi keel shaft contains 198 parts, 14 movable joints and 3-level linkage structure, which can provide better screen protection while realizing thinness.

Xiaomi MIX Fold 3 (right) Image source: Xiaomi official website screenshot

The "double rotating water drop hinge" was first proposed by Huawei in 2021. At that time, Yu Chengdong said at the press conference that Huawei’s water drop hinge is an exclusive patent, and other companies must use Huawei’s patented technology if they want to realize seamless folding screen.

Huawei Mate-x folding screen mobile phone Image source: national business daily (data map)　

It is worth mentioning that,This is not the first time that Huawei and Xiaomi have had differences on intellectual property issues.On January 17th this year, China National Intellectual Property Administration accepted the patent infringement case brought by Huawei, the claimant, against Xiaomi. Judging from the contents of the patents, the above four patents involved in disputes are respectively: method and device for sending control signaling, method for feeding back ACK/NACK information during carrier aggregation, base station and user equipment, method and terminal for acquiring panoramic images, screen locking method and mobile terminal.

On March 1, Xiaomi responded: "The two sides are actively negotiating on patent licensing." Since then, Xiaomi has successively initiated requests for invalidation of four patents involved in Huawei’s case, and China National Intellectual Property Administration conducted oral trials after accepting them. In September this year, China National Intellectual Property Administration declared that "the patent right will remain valid".

On September 13th this year, Huawei and Xiaomi announced a global patent cross-licensing agreement, which covers communication technologies including 5G. When talking about whether the signing of the new agreement will affect the previous patent disputes, Xiaomi Group once responded exclusively to the reporter of national business daily: "The previous legal procedures will be resolved according to this agreement."

By the end of 2022, Huawei had more than 120,000 valid authorized patents in the world, and was in a leading position in many mainstream standard patent fields such as mobile communication, short-range communication and codec. In 2022, Huawei’s patent licensing revenue was about 560 million US dollars.

Third, the competition for folding screen mobile phones is becoming increasingly fierce.

Both the "double-rotating water drop hinge" and the "keel hinge" are key components of the folding screen mobile phone:It is an important mechanical "joint" to support the flexible screen, control the rotation range and realize the shape change of the mobile phone; At the same time, it is also the key to determine the completion of folding screen mobile phone products, which tests the technical accumulation of major mobile phone manufacturers.

In this context, the "dark horse" of folding screen mobile phones has become a cluster of flames in the winter of mobile phone consumption. From the appearance, the innovative and personalized appearance of the folding screen mobile phone relieves consumers’ aesthetic fatigue of the traditional straight mobile phone; Different folding methods, such as left and right folding, up and down folding, internal folding and external folding, also bring new experiences to consumers.

According to Counterpoint’s forecast, the shipment of folding screen mobile phones in China will exceed 5 million units in 2023, and it is expected to explode in 2024, reaching 10 million units. In 2025, the folding screen market in China will reach 17 million units. Omdia predicts that by 2026, the global shipment of folding screen smartphones will reach 61 million units, with a compound annual growth rate of 46.6% from 2021 to 2026.

In the face of the rare incremental market, almost all major mobile phone brands except Apple have entered the folding track.Going to the folding screen has become a tacit strategy for mobile phone manufacturers, especially those who compete for high-end share.

As for the current market share of each company, the report released by IDC, an international data company, shows that the market shipment of folding screen mobile phones in China reached 1.96 million units in the third quarter, up 90.4% year-on-year.

In terms of manufacturers, Huawei ranked first in the market share in the first three quarters of this year, reaching 31.7%; OPPO ranked second with a share of 17.9%; Samsung ranked third, accounting for 15.4% of the market; Glory gained 15.1% market share, ranking fourth; Vivo ranked fifth, with a share of 12.7%, and X Flip continued to sell well for half a year. Xiaomi’s market share is 5.2%, and the first sale of MIX Fold3 is obviously better than that of the previous generation.

This article comes from WeChat WeChat official account:Headline of each warp (ID: nbdtoutiao)Author: Yang Hui, Jing Wong, Editor: Cheng Peng, Zhang Haini, Du Hengfeng.

　　CCTV News:The Central Meteorological Observatory continued to issue a typhoon red warning at 18: 00 on September 1:

　　The center of Typhoon Sura No.9 this year (super typhoon level) is located at 5 o’clock in the afternoon today (September 1) in the northeastern South China Sea, about 110 kilometers south-east of Hong Kong, that is, 22.0 degrees north latitude and 115.1 degrees east longitude. The maximum wind force near the center is 17 (58 meters per second), the lowest pressure in the center is 925 hectopascals, and the radius of the seven-level wind circle is 250-280 kilometers.

　　It is estimated that "Sura" will move from north to west at a speed of 10-15 kilometers per hour, and its intensity will slowly weaken. It will land or brush the coast from Taishan to Shenzhen in Guangdong in the early morning of September 2 (strong typhoon level, 42-50 m/s, 14-15), and then move to the south-west direction.

　　In addition, the center of the 11th typhoon "HAIKUI" this year is located at 5 o’clock in the afternoon today (September 1st) in the northwest Pacific Ocean about 770 kilometers south-east of Taipei City, Taiwan Province Province, which is 22.4 degrees north latitude and 128.5 degrees east longitude. The maximum wind force near the center is 12 (33m/s), and the lowest pressure in the center is 975 hectopascals, with a seven-level wind circle.

　　It is estimated that "Anemone" will move westward at a speed of 15-20km/h, and its intensity will gradually increase, with the strongest typhoon level (42-45m/s, level 14). It will land on the eastern coast of Taiwan Province Island around the evening of the 3rd, then pass through Taiwan Province Island and gradually approach the coast of Fujian.

　　Gale forecast:From 20: 00 on September 1 to 20: 00 on September 2, affected by Sura, the Taiwan Province Strait, the central and southern South China Sea, the waters near Nansha Islands, zhongsha islands and Huangyan Island, and the coastal areas of Zhejiang will have 6-7 grades and gusts of 8-9 winds; There will be strong winds of 7-9 grades and gusts of 10-11 grades in the northwest of the South China Sea, Fujian coastal areas, Guangdong coastal areas, the Pearl River Estuary, Hong Kong and Macao, etc., and there will be strong winds of 10-12 grades in some of the above sea areas or areas, and the winds in the nearby seas or areas passing by the "Sura" center will be 13-17 grades and gusts of 17 or above; Affected by Anemone, there are 6-7 grades in the south and east of the East China Sea and east of Taiwan Province, 8-10 grades in some sea areas, and 11-12 winds in gusts.

　　Precipitation forecast: From 20: 00 on September 1 to 20: 00 on September 2, due to the influence of Sura, there were heavy rains in southeastern Fujian, central and southern Guangdong, Hong Kong and Macao, among which there were heavy rains in parts of southern Guangdong, Hong Kong and Macao, and local heavy rains (250-280 mm).

　　Defense guide:

　　1. The government and relevant departments shall, in accordance with their duties, do a good job in typhoon prevention and emergency rescue.

　　2. Water operations and passing ships in relevant waters should return to Hong Kong to take shelter from the wind, strengthen port facilities, and prevent ships from anchoring, grounding and collision.

　　3. Stop large-scale indoor and outdoor gatherings and dangerous outdoor operations such as high altitude.

　　4. Reinforce or dismantle structures that are easy to be blown by the wind. Personnel should not go out at will. They should stay in windproof and safe places as far as possible, so as to ensure that the elderly and children stay in the safest place at home, and the dangerous people will be transferred in time. When the typhoon center passes by, the wind will decrease or stay still for a period of time. Remember that the strong wind will suddenly blow and you should continue to stay in a safe place to avoid the wind.

　　5. Relevant areas should pay attention to prevent flash floods and geological disasters that may be caused by heavy precipitation.

　　The good news of warm spring is coming! The "Detailed Rules for the Implementation of Chengdu Residence Permit Points Management Measures (Trial)", which is concerned by the public, was published on the website of Chengdu Municipal People’s Government on March 9, and is valid for two years.

　　As long as you hold a residence permit in Chengdu and meet the relevant conditions, you can participate in the application for points entry. Huaxi Dushi Bao-the cover journalist combed and found that citizens can get corresponding points by doing nine major items such as charity, blood donation and volunteer service, while those with personal bad credit records and illegal crimes will be reduced accordingly.

　　The standard score of the starting line for households is 100 points, and applicants are ranked according to the level of points.

　　The standard score of integral is 100 points. If the total score of residence permit reaches the standard score and meets the following conditions at the same time, you are eligible to apply for points:

　　The applicant holds the residence permit of this city (within the validity period), and the age is under 55 for men and 50 for women. The applicant has paid the basic old-age insurance for urban workers and the basic medical insurance for urban workers for more than 5 years in accordance with the relevant provisions of the state, province and city within the administrative area of this Municipality. At the same time, he has no criminal record and has not participated in organizations or activities prohibited by the state.

　　The annual residence permit points into the household index plan, released after examination and approval by the municipal government. Within 10 days after the announcement of the results of the points, Chengdu Population Service Management Office will rank the points in the order of high and low according to the application of the holders who have reached the standard score, and rank the points with the same points according to the years of participation and residence, and determine the list of households according to the annual residence permit points entry index plan, which will be publicized on the website of Chengdu residence permit points public service platform for five days.

　　Nine items plus points

　　You can get extra points by adding 25 points for charity volunteer service at the highest time.

　　In what areas should the applicant score points? Chengdu has listed nine points, many of which are "sub-items". As long as applicants have stable housing, occupation and social security, they can get points. Among them, the highest individual score is awarded by the state, with 25 points at a time.

　　　Pay social insurance index

　　If the applicant participates in the basic old-age insurance and basic medical insurance for urban workers in accordance with the relevant provisions of the state, province and city within the administrative area of this Municipality, and continuously pays the monthly fee for 12 months, 10 points can be accumulated; If it is over 6 months but less than 12 months, 5 points will be accumulated; No points for less than 6 months.

　　Legal and stable residence index

　　The applicant actually lives in the house in this city, and obtains the own residence with the property right certificate or the house ownership certificate, plus 10 points, and the continuous residence is calculated by 1 point/year; The housing that has signed a formal housing lease contract and gone through the lease registration and filing shall be counted as 1 point/year for continuous residence. If there are two or more self-owned residences and rented houses within the scope of this Municipality, only the houses with the same residence permit address can be added, without accumulation.

　　Educational background index

　　Applicants who do not meet the requirements for talent introduction in this Municipality, but have obtained full-time colleges and universities recognized by the Ministry of Education and other part-time higher education colleges (including higher vocational colleges) or above, add 10 points.

　　Indicators to guide the rational distribution of population

　　Since January 1, 2018, the applicant has participated in social insurance for urban workers in the social security agencies of provinces, cities, districts (cities) and counties within the administrative area of this Municipality, and the registered place of the employer (including individual industrial and commercial households) is calculated cumulatively at 20 points/year in the eastward area and the southward area, and 10 points/year in the northward area, with no extra points in other areas.

　　Guiding population gradient transfer index

　　Since January 1, 2018, if the applicant’s residence is transferred from Jinjiang District, Qingyang District, jinniu district, Wuhou District, chenghua district and Chengdu High-tech South Zone and West Zone to other administrative areas of this Municipality, 5 points will be added for each full year; If the applicant’s place of employment and residence are transferred to other administrative areas of this Municipality, 10 points will be added for each full year.

　　　Urgent need for indicators of jobs (occupations)

　　If the applicant belongs to the catalogue of urgently needed jobs (occupations) in this Municipality, add 10 points.

　　Individual contribution index

　　Individual contribution indicators are divided into five aspects:

　　Applicants who have been commended by the Party committee or government of the country, Sichuan Province and Chengdu City will be awarded 25 points at the national level, 20 points at the provincial level and 15 points at the municipal level respectively, and the above points will not be accumulated. Including model workers (including those who enjoy the treatment of model workers), moral models, courageous models, craftsmen, etc.

　　The applicant pays personal income tax in this city according to law, and if the annual tax payment in the previous natural year reaches 10,000 yuan, add 2 points; If it exceeds 10,000 yuan, it shall be calculated by adding 0.2 points for every 1,000 yuan, with a maximum of 10 points.

　　Applicants who participate in volunteer service are registered in Chengdu Volunteer Network (APP) with their real names and obtained the length of volunteer service. The application points are accumulated for 25 hours of volunteer service in the previous natural year plus 2 points, and 1 point is added for every 2 hours after reaching 25 hours, with a maximum of 10 points.

　　Applicants who participate in charitable donations within the scope of charitable organizations registered in this Municipality can get extra points. Donations of funds or materials (equivalent to RMB) in the past 3 years will be calculated by adding 2 points for each full RMB 1,000, with a maximum of 10 points.

　　The applicant shall add 2 points for each donation of 200ml whole blood, 1 point for each increase of 100ml whole blood, and 2 points for each donation of a therapeutic amount of apheresis platelets from June 1st to May 31st of the reporting year, with a maximum of 10 points.

　　Encourage innovation and entrepreneurship indicators

　　Applicants who participated in the Innovation and Entrepreneurship Competition won national, Sichuan or Chengdu municipal awards, with 15 points, 10 points and 5 points respectively; The applicant in the city to start a business to absorb more than 5 people employment plus 10 points; If the applicant invests or starts a business in this city’s science and technology business incubator and Zhongchuang Space, 10 points will be added if certain conditions are met.

　　Age index

　　If the applicant is under 45 years old, add 10 points, and the deadline for calculating the age is May 31st of the year when applying for points.

　　Decrement index

　　50 points for illegal crimes at a time.

　　Personal bad credit records, personal criminal records, etc. will be reduced.

　　Personal bad credit record index refers to the applicant’s bad records in personal credit, industrial and commercial taxation and other aspects in the past three years, with 10 points deducted for each item. Individual criminal record index refers to the applicant who violates relevant laws and regulations, is punished for criminal offences, and participates in organizations or activities prohibited by the state, with 50 points deducted for each item; By the administrative law enforcement organs sentenced to administrative detention, compulsory detoxification, each minus 20 points.

　　Violation of family planning policy indicators, illegal birth behavior reduced by 50 points.

　　Detailed question and answer

　　Guide the population to rationally distribute the three bonus areas.

　　In guiding the rational distribution of population, which specific areas can be added?

　　The specific bonus areas are: Dongjin area (the trial scope includes Tianfu International Airport New City, Jianzhou New City and Huaizhou New City); Nantuo area (the trial scope includes Luxi Zhigu Science and Technology Innovation and High-tech Industrial Service Functional Zone in Tianfu New District, Tianfu Center Headquarters Economic Functional Zone in Tianfu New District, Tianfu Center International Convention and Exhibition Functional Zone in Tianfu New District, Tianfu New District Southern District Industrial Park and Tianfu New District Qionglai Industrial Park); Northern Reform Area (the trial scope includes qingbaijiang district Advanced Materials Industrial Park, qingbaijiang district International Railway Port Service Industry Cluster, Xindu High-tech Industrial Park, Pengzhou Chengdu Aviation Power Industrial Park).

　　How to understand "own residence" and "housing lease" in the index of legal and stable residence?

　　Self-owned residence refers to the housing that has obtained the title certificate of immovable property or the title certificate of house ownership within the city, including the housing owned by the applicant alone or jointly with his spouse, the housing owned by the applicant and others with a share of not less than 50%, and the housing owned by the applicant’s spouse alone.

　　Housing lease, including the state-owned directly-managed public houses rented by the applicant alone or jointly with others, the houses with legal property rights rented by employees, public rental houses (including low-rent houses) and other legally rented houses.

　　How to understand "residence transfer" and "applicant’s employment transfer" in the index of guiding population gradient transfer?

　　The transfer of residence refers to the change of the applicant’s actual residence address, which is subject to the change of address recorded in the residence permit.

　　Transfer of the applicant’s employment place: one is that the registered place of the employer (including individual industrial and commercial households) where the applicant is located is changed from Jinjiang District, Qingyang District, jinniu district, Wuhou District, chenghua district and Chengdu High-tech South Zone and West Zone to other administrative areas of this Municipality, and the social security participation relationship will not change within the scope of Chengdu (including provincial-level agencies); The other is that the applicant’s former employer (including individual industrial and commercial households) is registered in Jinjiang District, Qingyang District, jinniu district, Wuhou District, chenghua district and Chengdu High-tech South Zone and West Zone. After leaving the original employer, the current employer (including individual industrial and commercial households) is registered in other administrative areas of this Municipality, and the social insurance participation relationship has changed in Chengdu (including provincial-level agencies). (Reporter Lai Fangjie)