The latest progress in the process optimization and stability improvement of third-generation cephalosporins in recent years was reviewed.The introduction of green chemistry,enzyme catalysis,nanotechnology,lyophilizat...The latest progress in the process optimization and stability improvement of third-generation cephalosporins in recent years was reviewed.The introduction of green chemistry,enzyme catalysis,nanotechnology,lyophilization,and nitrogen-filled packaging technologies can only improve production efficiency and reduce the generation of by-products,but also significantly extend the shelf life of drugs.In the future,process automation and intelligent technology will further optimize the large-scale production process,and the combination of nanotechnology and precision drug delivery will promote the improvement of effect in clinical applications.展开更多
Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance me...Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism.We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib.Method:A 53-year-old,never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer(NSCLC)developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg.Salvage therapy with zorifertinib(200 mg BID)plus firmonertinib(80 mg qd)was initiated.Results:Within 14 days,the coma resolved.Karnofsky Performance Status improved from 20 to 70.Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1.Only grade 1-2 diarrhea,rash,and transaminitis occurred and resolved with symptomatic care.Conclusion:The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure.Prospective validation is warranted.展开更多
The breeding and large-scale application of hybrid rice contribute significantly to the food supply worldwide.Currently,hybrid seed production uses cytoplasmic male sterile(CMS)lines or photoperiod/thermo-sensitive ge...The breeding and large-scale application of hybrid rice contribute significantly to the food supply worldwide.Currently,hybrid seed production uses cytoplasmic male sterile(CMS)lines or photoperiod/thermo-sensitive genic male sterile(PTGMS)lines as female parent.Despite huge successes,both systems have intrinsic problems.CMS systems are mainly restricted by the narrow restorer resources that make it difficult to breed superior hybrids,while PTGMS systems are limited by conditional sterility of the male sterile lines that makes the propagation of both PTGMS seeds and hybrid seeds vulnerable to unpredictable climate changes.Recessive nuclear male sterile(NMS)lines insensitive to environmental conditions are widely distributed and are ideal for hybrid rice breeding and production,but the lack of effective ways to propagate the pure NMS lines in a large scale renders it impossible to use them for hybrid rice production.The development of"the third-generation hybrid rice technology"enables efficient propagation of the pure NMS lines in commercial scale.This paper discusses the establishment of"the thirdgeneration hybrid rice technology"and further innovations.This new technology breaks the limitations of CMS and PTGMS systems and will bring a big leap forward in hybrid rice production.展开更多
During the past thirty years, two generations of low alloy steels(ferrite/pearlite followed by bainite/martensite) have been developed and widely used in structural applications. The third-generation of low alloy stee...During the past thirty years, two generations of low alloy steels(ferrite/pearlite followed by bainite/martensite) have been developed and widely used in structural applications. The third-generation of low alloy steels is expected to achieve high strength and improved ductility and toughness, while satisfying the new demands for weight reduction, greenness, and safety. This paper reviews recent progress in the development of third-generation low alloy steels with an M^3 microstructure, namely, microstructures with multi-phase, meta-stable austenite, and multi-scale precipitates. The review summarizes the alloy designs and processing routes of microstructure control, and the mechanical properties of the alloys.The stabilization of retained austenite in low alloy steels is especially emphasized. Multi-scale nano-precipitates, including carbides of microalloying elements and Cu-rich precipitates obtained in third-generation low alloy steels, are then introduced. The structure–property relationships of third-generation alloys are also discussed. Finally, the promises and challenges to future applications are explored.展开更多
The existing numerical models for nearshore waves are briefly introduced, and the third-generation numerical model for shallow water wave, which makes use of the most advanced productions of wave research and has been...The existing numerical models for nearshore waves are briefly introduced, and the third-generation numerical model for shallow water wave, which makes use of the most advanced productions of wave research and has been adapted well to be used in the environment of seacoast, lake and estuary area, is particularly discussed. The applied model realizes the significant wave height distribution at different wind directions. To integrate the model into the coastal area sediment, sudden deposition mechanism, the distribution of average silt content and the change of sediment sudden deposition thickness over time in the nearshore area are simulated. The academic productions can give some theoretical guidance to the applications of sediment sudden deposition mechanism for stormy waves in the coastal area. And the advancing directions of sediment sudden deposition model are prospected.展开更多
Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on ...Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.展开更多
The Third-Generation Poetry of China （namely Post-misty Poetry too） initiated with the introduction of Western modernist poetry, especially sorts of American Post-modernist poetry schools into China. ＂The relation ...The Third-Generation Poetry of China （namely Post-misty Poetry too） initiated with the introduction of Western modernist poetry, especially sorts of American Post-modernist poetry schools into China. ＂The relation between American poetry and Chinese poetry has a long history, which lies in the influences on the creation of the Third-Generation poets. This influence is probably unprecedented in its depth and breadth.＂ ＂Irrational association＂ and ＂leaping images＂ proposed by American Deep Image poets influenced by Freudian and Jungian unconscious perception gained an extraordinary appreciation among the Third-Generation poets who were in pursuit constantly of the experiments on poetic form and language. This paper mainly discusses the influences of American Deep Image on the Third-Generation poets of China through a case study of WANG Yin and CHEN Dongdong＇s poems.展开更多
The development of measurement geometry for medical X-ray computed tomography （CT） scanners was carried out from the first to the fourth-generation. This concept has also been applied for imaging of industrial proce...The development of measurement geometry for medical X-ray computed tomography （CT） scanners was carried out from the first to the fourth-generation. This concept has also been applied for imaging of industrial processes such as pipe flows or for improving design, operation, optimization and troubleshooting. Nowadays, gamma CT permits to visualize failure equipment points in three-dimensional analysis and in sections of chemical and petrochemical industries. The aim of this work is the development of the mechanical system on a third-generation industrial CT scanner to analyze laboratorial process columns which perform highly efficient separation, turning the ^6oCo, ^75Se, ^137Cs and/or ^192Ir sealed gamma-ray source（s） and the NaI（Tl） multidetector array. It also has a translation movement along the column axis to obtain as many slices of the process flow as needed. The mechanical assembly for this third-generation industrial CT scanner is comprised by strength and rigidity structural frame in stainless and carbon steels, rotating table, source shield and collimator with pneumatic exposure system, spur gear system, translator, rotary stage, drives and stepper motors. The use of suitable spur gears has given a good repeatability and high accuracy in the degree of veracity. The data acquisition boards, mechanical control interfaces, software for movement control and image reconstruction were specially development. A multiphase phantom capable to be setting with solid, liquid and gas was testing. The scanner was setting for 90 views and 19 projections for each detector totalizing 11,970 projections. Experiments to determine the linear attenuation coefficients of the phantom were carried out which applied the Lambert-Beer principle. Results showed that it was possible to distinguish between the phases even the polymethylmethacrylate and the water have very similar density and linear attenuation coefficients. It was established that the newly developed third-generation fan-beam arrangement gamma scanner unit has a good spatial resolution acceptable given the size of the used phantom in this study. The tomografic reconstruction algorithm in used 60 ~ 60 pixels images was the Alternative Minimization （AM） technique and was implemented in MATLAB and VB platforms. The mechanical system presented a good performance in terms of strength, rigidity, accuracy and repeatability with great potential to be used for education or program which dedicated to training chemical and petrochemical industry professionals and for industrial process optimization in Brazil.展开更多
A shallowly submerged hydrofoil often induces disturbances on the free water surface by generating numerous vortex structures,leading to phenomena such as wave breaking and droplet splashing.These phenomena involve va...A shallowly submerged hydrofoil often induces disturbances on the free water surface by generating numerous vortex structures,leading to phenomena such as wave breaking and droplet splashing.These phenomena involve various physical mechanisms.In this study,the third-generation vortex identification technique,Liutex,is employed to perform a detailed analysis of the vortex structures generated by the hydrofoil near the free surface.It is observed that these coherent vortex structures strongly entrain surrounding fluid,resulting in air entrainment and bubble sweep-down phenomena.We analyze the bubble dynamics in terms of bubble number density,volume distribution,and number distribution,revealing the dynamic characteristics of bubbles under the influence of vortex structures.Additionally,by tracking the vortex structures,two distinct forms of air entrainment are identified.The analysis of bubble motion using Liutex demonstrates the evolution and distribution patterns of bubble sizes in the turbulent flow field.The results indicate that the third-generation vortex identification technique,Liutex,effectively explains the mechanisms behind free surface breaking induced by the shallowly submerged hydrofoil.展开更多
Rice is a major cereal crop for China. The development of the ‘‘three-line" hybrid rice system based on cytoplasmic male sterility in the 1970 s(first-generation) and the ‘‘two-line" hybrid rice system b...Rice is a major cereal crop for China. The development of the ‘‘three-line" hybrid rice system based on cytoplasmic male sterility in the 1970 s(first-generation) and the ‘‘two-line" hybrid rice system based on photoperiod-and thermo-sensitive genic male-sterile lines(second-generation)in the 1980 s has contributed significantly to rice yield increase and food security in China. Here we describe the development and implementation of the ‘‘third-generation" hybrid rice breeding system that is based on a transgenic approach to propagate and utilize stable recessive nuclear male sterile lines, and as such, the male sterile line and hybrid rice produced using such a system is nontransgenic. Such a system should overcome the intrinsic problems of the ‘‘first-generation" and‘‘second-generation" hybrid rice systems and hold great promise to further boost production of hybrid rice and other crops.展开更多
Although the clinical efficacies of third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase in-hibitors(TKIs)such as osimertinib in the treatment of non-small cell lung cancer(NSCLC)with EGFR-activatin...Although the clinical efficacies of third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase in-hibitors(TKIs)such as osimertinib in the treatment of non-small cell lung cancer(NSCLC)with EGFR-activating mutations are promising,drug-acquired resistance inevitably occurs whether they are used as first-line or second-line treatment.Therefore,managing the acquired resistance to third-generation EGFR-TKIs is crucial in the clinic for improving patient survival.Great efforts have been made to develop potentially effective strategies or regimens for the treatment of EGFR-mutant NSCLC patients after relapse following these TKIs therapies with the hope that patients will continue to benefit from treatment through overcoming acquired resistance.Although this approach,which aims to overcome drug-acquired resistance,is necessary and important,it is a passive practice.Taking pre-ventive action early before disease progression to manage the unavoidable development of acquired resistance offers an equally important and efficient approach.We strongly believe that early preventive interventions using effective and tolerable combination regimens that interfere with the process of developing acquired resistance may substantially improve the outcomes of EGFR-mutant NSCLC treatment with third-generation EGFR-TKIs.Thus,this review focuses on discussing the scientific rationale and mechanism-driven strategies for delaying and even preventing the emergence of acquired resistance to third-generation EGFR-TKIs,particularly osimertinib.展开更多
Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy...Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy physics in the last two decades,a new-generation Tau-Charm factory,called the Super Tau-Charm Facility(STCF),has been actively promoted by the particle physics community in China.STCF has the potential to address fundamental questions such as the essence of color confinement and the matter-antimatter asymmetry within the next decades.The main design goals of the STCF are a center-of-mass energy ranging from 2 to 7 GeV and a luminosity surpassing 5×10^(34)cm^(−2)s^(−1)that is optimized at a center-of-mass energy of 4 GeV,which is approximately 50 times that of the currently operating Tau-Charm factory-BEPCII.The STCF accelerator has two main parts:a double-ring collider with a crab-waist collision scheme and an injector that provides top-up injections for both electron and positron beams.As a typical third-generation electron-positron circular collider,the STCF accelerator faces many challenges in both accelerator physics and technology.In this paper,the conceptual design of the STCF accelerator complex is presented,including the ongoing efforts and plans for technological research and develop-ment,as well as the required infrastructure.The STCF project aims to secure support from the Chinese central government for its construction during the 15th Five-Year Plan(2026-2030).展开更多
AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55...AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55 eyes)with postoperative endophthalmitis were retrospectively included in this study with their medical records.Intraocular fluid samples were examined by NTS and microbial culture.All included patients had undergone examinations including measurement of best corrected visual acuity(BCVA)and intraocular pressure(IOP),slit-lamp biomicroscopy,and indirect ophthalmoscopy;additionally,they underwent B-ultrasound,anterior segment photography,and fundus photography if necessary.RESULTS:Among 55 patients with postoperative endophthalmitis,the age was 65.25±15.04y and there were 30 female(54.54%)patients.Forty-one(74.54%)vitreous humor samples and fourteen(25.45%)aqueous humor samples were sent for both NTS and microbial culture.NTS had a notable higher detection rate than microbial culture in detecting pathogens(90.91%vs 38.18%,χ^(2)=33.409,P<0.001).NTS exhibited high sensitivity of pathogen detection in both microbial culture positive and negative samples(100%and 85.29%,respectively).In 16 of 21(76.19%)patients who showed culture-positivity,their results corresponded with those of NTS.Moreover,in two patients(9.52%),NTS showed a better species resolution than microbial culture;in three patients(14.28%),NTS identified additional pathogens.As for fungus,the positive detection rate of NTS was significantly higher than that of microbial culture(20%vs 3.64%,χ^(2)=7.066,P=0.008).Also,NTS could detect multi-infection by bacteria and fungi than microbial culture(32.73%vs 0,χ^(2)=21.522,P<0.001).NTS could detect bacteria as well as fungi simultaneously within 48h in all patients.Meanwhile,NTS had a shorter detection time than microbial culture(1.13±0.34 vs 2.67±0.55d,Z=-9.218,P<0.001).After the NTS results were obtained,15 patients received additional intravitreal/intracameral anti-infection treatment.At follow-up,there was a statistically significant improvement in the visual acuity relative to the baseline(Z=−5.222,P<0.001).CONCLUSION:NTS can provide rapid identification and highly sensitive detection of pathogens among patients with postoperative endophthalmitis,which can guide anti-infection treatment and improve visual prognosis.展开更多
In the history of bridge engineering, demand has always been the primary driving force for development. Driven by the huge demand for construction since China’s reform and opening-up, Chinese bridge has leapt forward...In the history of bridge engineering, demand has always been the primary driving force for development. Driven by the huge demand for construction since China’s reform and opening-up, Chinese bridge has leapt forward both quantitatively and qualitatively in three major stages, by completing the transition from “follower” to “competitor,” and nally to “leader.” A new future is emerging for Chinese bridge engi- neering. As an important part of China’s transportation infrastructure, the bridge engineering industry is facing challenges in this new era on how to support the construction of a new form of transportation. This paper provides a summary of the status of bridge technology in China, based on a basic analysis of stock demand, incremental demand, and management demand. It is our belief that the Chinese bridge engi- neering industry must ful ll three outstanding requirements: construction ef ciency, management effec- tiveness, and long-term service. Intelligent technology based on information technology provides a new opportunity for innovation in bridge engineering. As a result, the development path of bridge engineering needs to be changed. This paper puts forward the idea of developing a third-generation bridge project that is characterized by intelligence, and discusses this project’s implications, development focus, and plan. In this way, this work provides a direction for the improvement of the core competitiveness of China’s bridge engineering industry.展开更多
The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary...The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.展开更多
BACKGROUND Infectious diseases are still one of the greatest threats to human health,and the etiology of 20%of cases of clinical fever is unknown;therefore,rapid identification of pathogens is highly important.Traditi...BACKGROUND Infectious diseases are still one of the greatest threats to human health,and the etiology of 20%of cases of clinical fever is unknown;therefore,rapid identification of pathogens is highly important.Traditional culture methods are only able to detect a limited number of pathogens and are time-consuming;serologic detection has window periods,false-positive and false-negative problems;and nucleic acid molecular detection methods can detect several known pathogens only once.Three-generation nanopore sequencing technology provides new options for identifying pathogens.CASE SUMMARY Case 1:The patient was admitted to the hospital with abdominal pain for three days and cessation of defecation for five days,accompanied by cough and sputum.Nanopore sequencing of the drainage fluid revealed the presence of orallike bacteria,leading to a clinical diagnosis of bronchopleural fistula.Cefoperazone sodium sulbactam treatment was effective.Case 2:The patient was admitted to the hospital with fever and headache,and CT revealed lung inflammation.Antibiotic treatment for Streptococcus pneumoniae,identified through nanopore sequencing of cerebrospinal fluid,was effective.Case 3:The patient was admitted to our hospital with intermittent fever and an enlarged neck mass that had persisted for more than six months.Despite antibacterial treatment,her symptoms worsened.The nanopore sequencing results indicate that voriconazole treatment is effective for Aspergillus brookii.The patient was diagnosed with mixed cell type classical Hodgkin's lymphoma with infection.CONCLUSION Three-generation nanopore sequencing technology allows for rapid and accurate detection of pathogens in human infectious diseases.展开更多
A third-generation horseradish peroxidase (HRP) biosensor has been developed by adsorbing HRP on multi-wall carbon nanotube (MWNTs) monolayer modified gold electrode surface. The assembly process was investigated by...A third-generation horseradish peroxidase (HRP) biosensor has been developed by adsorbing HRP on multi-wall carbon nanotube (MWNTs) monolayer modified gold electrode surface. The assembly process was investigated by electrochemical and spectroscopic techniques. Results showed that the immobilized HRP exhibited direct electrochemical behavior toward the reduction of H2O2. The resulting biosensor shows a fast amperometric response (<2 s) to H2O2. The linear response range was from 5.0×10-7～1.0×10-5 mol/L with a detection limit of 1.0×10-7mol/L. Moreover, the biosensor has a good reproducibility, and long-term stability.展开更多
[Objectives]This study was conducted to investigate the effects of adding compound probiotics on the growth performance and intestinal flora of Kunming mice.[Methods]Twelve healthy 2-week-old Kunming male mice with bo...[Objectives]This study was conducted to investigate the effects of adding compound probiotics on the growth performance and intestinal flora of Kunming mice.[Methods]Twelve healthy 2-week-old Kunming male mice with body weight of(11.09±0.43)g were selected.They were randomly divided into two treatment groups,namely blank control group(NC)and compound probiotics group(CB+LR+BS),with six mice in each group.The two groups were fed with commercial basal diet,and the compound probiotic experimental group was fed with basal diet supplemented with compound probiotics,in which the contents of Clostridium butyricum spores,Lactobacillus reuteri and Bacillus subtilis spores were 1×1010,1×1011 and 1×1010 CUF/kg,respectively.The body weight,feed intake and water intake of mice were counted every 4 d,and the experimental period was 13 d.On the 13 th day,the cecal contents of the mice were collected for analysis.[Results]There was no significant change in body weight and feed intake when compound probiotics were added to the diet.However,the addition of compound probiotics reduced the abundance of harmful bacteria such as Escherichia coli,urease-negative Helicobacter typhlonius and Salmonella enterica,while increasing the abundance of beneficial bacteria such as Anaerostipes hadrus,and the contents of IgG and IgM increased significantly(P<0.05).[Conclusions]In summary,the addition of compound probiotics could significantly improve the structure of intestinal microbial flora,increase the quantity of beneficial bacteria,reduce the quantity of harmful bacteria,and improve the immune function of mice.展开更多
Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing （SGS） technologies, making it well-suited for unsolved problems in genome, tran...Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing （SGS） technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation （SV） in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with dis- eases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Addition- ally, PacBio＇s sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone.展开更多
基金Supported by the Funds from Central Government for Guiding Local Science and Technology Development(ZY20230102)Planning Project of Scientific Research and Technology Development in Guilin(20220104-4,20210202-1)Science and Technology Planing Project of Guangxi(Guike AB24010263).
文摘The latest progress in the process optimization and stability improvement of third-generation cephalosporins in recent years was reviewed.The introduction of green chemistry,enzyme catalysis,nanotechnology,lyophilization,and nitrogen-filled packaging technologies can only improve production efficiency and reduce the generation of by-products,but also significantly extend the shelf life of drugs.In the future,process automation and intelligent technology will further optimize the large-scale production process,and the combination of nanotechnology and precision drug delivery will promote the improvement of effect in clinical applications.
文摘Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism.We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib.Method:A 53-year-old,never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer(NSCLC)developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg.Salvage therapy with zorifertinib(200 mg BID)plus firmonertinib(80 mg qd)was initiated.Results:Within 14 days,the coma resolved.Karnofsky Performance Status improved from 20 to 70.Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1.Only grade 1-2 diarrhea,rash,and transaminitis occurred and resolved with symptomatic care.Conclusion:The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure.Prospective validation is warranted.
基金supported by the National Natural Science Foundation of China(U1901203)Natural Science Foundation of Guangdong Province(2018B030308008 and 2019A1515110671)+2 种基金Major Program of Guangdong Basic and Applied Research(2019B030302006)Shenzhen Commission on Innovation and Technology Programs(JCYJ20180507181837997)China Postdoctoral Science Foundation(2019M662957)。
文摘The breeding and large-scale application of hybrid rice contribute significantly to the food supply worldwide.Currently,hybrid seed production uses cytoplasmic male sterile(CMS)lines or photoperiod/thermo-sensitive genic male sterile(PTGMS)lines as female parent.Despite huge successes,both systems have intrinsic problems.CMS systems are mainly restricted by the narrow restorer resources that make it difficult to breed superior hybrids,while PTGMS systems are limited by conditional sterility of the male sterile lines that makes the propagation of both PTGMS seeds and hybrid seeds vulnerable to unpredictable climate changes.Recessive nuclear male sterile(NMS)lines insensitive to environmental conditions are widely distributed and are ideal for hybrid rice breeding and production,but the lack of effective ways to propagate the pure NMS lines in a large scale renders it impossible to use them for hybrid rice production.The development of"the third-generation hybrid rice technology"enables efficient propagation of the pure NMS lines in commercial scale.This paper discusses the establishment of"the thirdgeneration hybrid rice technology"and further innovations.This new technology breaks the limitations of CMS and PTGMS systems and will bring a big leap forward in hybrid rice production.
基金financially supported by the National Natural Science Foundation of China (No. 51701012)the National Basic Research Program of China (973 Program: No. 2010CB630801)the Fundamental Research Funds for the Central Universities (No. FRF-TP-17-004A1)
文摘During the past thirty years, two generations of low alloy steels(ferrite/pearlite followed by bainite/martensite) have been developed and widely used in structural applications. The third-generation of low alloy steels is expected to achieve high strength and improved ductility and toughness, while satisfying the new demands for weight reduction, greenness, and safety. This paper reviews recent progress in the development of third-generation low alloy steels with an M^3 microstructure, namely, microstructures with multi-phase, meta-stable austenite, and multi-scale precipitates. The review summarizes the alloy designs and processing routes of microstructure control, and the mechanical properties of the alloys.The stabilization of retained austenite in low alloy steels is especially emphasized. Multi-scale nano-precipitates, including carbides of microalloying elements and Cu-rich precipitates obtained in third-generation low alloy steels, are then introduced. The structure–property relationships of third-generation alloys are also discussed. Finally, the promises and challenges to future applications are explored.
文摘The existing numerical models for nearshore waves are briefly introduced, and the third-generation numerical model for shallow water wave, which makes use of the most advanced productions of wave research and has been adapted well to be used in the environment of seacoast, lake and estuary area, is particularly discussed. The applied model realizes the significant wave height distribution at different wind directions. To integrate the model into the coastal area sediment, sudden deposition mechanism, the distribution of average silt content and the change of sediment sudden deposition thickness over time in the nearshore area are simulated. The academic productions can give some theoretical guidance to the applications of sediment sudden deposition mechanism for stormy waves in the coastal area. And the advancing directions of sediment sudden deposition model are prospected.
文摘Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.
文摘The Third-Generation Poetry of China （namely Post-misty Poetry too） initiated with the introduction of Western modernist poetry, especially sorts of American Post-modernist poetry schools into China. ＂The relation between American poetry and Chinese poetry has a long history, which lies in the influences on the creation of the Third-Generation poets. This influence is probably unprecedented in its depth and breadth.＂ ＂Irrational association＂ and ＂leaping images＂ proposed by American Deep Image poets influenced by Freudian and Jungian unconscious perception gained an extraordinary appreciation among the Third-Generation poets who were in pursuit constantly of the experiments on poetic form and language. This paper mainly discusses the influences of American Deep Image on the Third-Generation poets of China through a case study of WANG Yin and CHEN Dongdong＇s poems.
文摘The development of measurement geometry for medical X-ray computed tomography （CT） scanners was carried out from the first to the fourth-generation. This concept has also been applied for imaging of industrial processes such as pipe flows or for improving design, operation, optimization and troubleshooting. Nowadays, gamma CT permits to visualize failure equipment points in three-dimensional analysis and in sections of chemical and petrochemical industries. The aim of this work is the development of the mechanical system on a third-generation industrial CT scanner to analyze laboratorial process columns which perform highly efficient separation, turning the ^6oCo, ^75Se, ^137Cs and/or ^192Ir sealed gamma-ray source（s） and the NaI（Tl） multidetector array. It also has a translation movement along the column axis to obtain as many slices of the process flow as needed. The mechanical assembly for this third-generation industrial CT scanner is comprised by strength and rigidity structural frame in stainless and carbon steels, rotating table, source shield and collimator with pneumatic exposure system, spur gear system, translator, rotary stage, drives and stepper motors. The use of suitable spur gears has given a good repeatability and high accuracy in the degree of veracity. The data acquisition boards, mechanical control interfaces, software for movement control and image reconstruction were specially development. A multiphase phantom capable to be setting with solid, liquid and gas was testing. The scanner was setting for 90 views and 19 projections for each detector totalizing 11,970 projections. Experiments to determine the linear attenuation coefficients of the phantom were carried out which applied the Lambert-Beer principle. Results showed that it was possible to distinguish between the phases even the polymethylmethacrylate and the water have very similar density and linear attenuation coefficients. It was established that the newly developed third-generation fan-beam arrangement gamma scanner unit has a good spatial resolution acceptable given the size of the used phantom in this study. The tomografic reconstruction algorithm in used 60 ~ 60 pixels images was the Alternative Minimization （AM） technique and was implemented in MATLAB and VB platforms. The mechanical system presented a good performance in terms of strength, rigidity, accuracy and repeatability with great potential to be used for education or program which dedicated to training chemical and petrochemical industry professionals and for industrial process optimization in Brazil.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.52131102,52471335)supported by the Research and Application Demonstration Project of Key Technologies for Safeguarding of Container Vessels in Ningbo Zhoushan Port Based on Intelligent Navigation(Grant No.ZJHG-FW-2024-27).
文摘A shallowly submerged hydrofoil often induces disturbances on the free water surface by generating numerous vortex structures,leading to phenomena such as wave breaking and droplet splashing.These phenomena involve various physical mechanisms.In this study,the third-generation vortex identification technique,Liutex,is employed to perform a detailed analysis of the vortex structures generated by the hydrofoil near the free surface.It is observed that these coherent vortex structures strongly entrain surrounding fluid,resulting in air entrainment and bubble sweep-down phenomena.We analyze the bubble dynamics in terms of bubble number density,volume distribution,and number distribution,revealing the dynamic characteristics of bubbles under the influence of vortex structures.Additionally,by tracking the vortex structures,two distinct forms of air entrainment are identified.The analysis of bubble motion using Liutex demonstrates the evolution and distribution patterns of bubble sizes in the turbulent flow field.The results indicate that the third-generation vortex identification technique,Liutex,effectively explains the mechanisms behind free surface breaking induced by the shallowly submerged hydrofoil.
基金support from the Ministry of Science and Technology of China (Grant Nos.2009AA101201 and 2011AA10A107)Hunan Province Government (Grant No.2009fj1012)+1 种基金Guangdong Province Government (Grant No.201001S0104725509)Shenzhen Municipal Government (Grant Nos.KQF201109160004A,JC201005280655A,CXZZ20140411140647863,NYSW 20140326010006,SWCYL20150331010020,and JSGG201 50508105340526),China
文摘Rice is a major cereal crop for China. The development of the ‘‘three-line" hybrid rice system based on cytoplasmic male sterility in the 1970 s(first-generation) and the ‘‘two-line" hybrid rice system based on photoperiod-and thermo-sensitive genic male-sterile lines(second-generation)in the 1980 s has contributed significantly to rice yield increase and food security in China. Here we describe the development and implementation of the ‘‘third-generation" hybrid rice breeding system that is based on a transgenic approach to propagate and utilize stable recessive nuclear male sterile lines, and as such, the male sterile line and hybrid rice produced using such a system is nontransgenic. Such a system should overcome the intrinsic problems of the ‘‘first-generation" and‘‘second-generation" hybrid rice systems and hold great promise to further boost production of hybrid rice and other crops.
基金I am thankful to Dr.Anthea Hammond in our department for editing the manuscript.Some of the work done in my lab was supported by the NIH/NCI R01 CA223220,R01 CA245386,UG1 CA233259 awards and Emory University Winship Cancer Institute lung cancer pilot funds.
文摘Although the clinical efficacies of third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase in-hibitors(TKIs)such as osimertinib in the treatment of non-small cell lung cancer(NSCLC)with EGFR-activating mutations are promising,drug-acquired resistance inevitably occurs whether they are used as first-line or second-line treatment.Therefore,managing the acquired resistance to third-generation EGFR-TKIs is crucial in the clinic for improving patient survival.Great efforts have been made to develop potentially effective strategies or regimens for the treatment of EGFR-mutant NSCLC patients after relapse following these TKIs therapies with the hope that patients will continue to benefit from treatment through overcoming acquired resistance.Although this approach,which aims to overcome drug-acquired resistance,is necessary and important,it is a passive practice.Taking pre-ventive action early before disease progression to manage the unavoidable development of acquired resistance offers an equally important and efficient approach.We strongly believe that early preventive interventions using effective and tolerable combination regimens that interfere with the process of developing acquired resistance may substantially improve the outcomes of EGFR-mutant NSCLC treatment with third-generation EGFR-TKIs.Thus,this review focuses on discussing the scientific rationale and mechanism-driven strategies for delaying and even preventing the emergence of acquired resistance to third-generation EGFR-TKIs,particularly osimertinib.
基金supported by the National Key R&D Program of China (2016YFC1303800)Key Lab System Project of Guangdong Science and Technology Department (2012A061400006/2017B030314120)+1 种基金Special Fund of Public Interest by National Health and Family Control Committee (201402031)the National Natural Science Foundation of China (81572282)
文摘Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated impressive activity in EGFR T790M-positive non-small cell lung cancer (NSCLC) progressed from prior EGFR-TKIs (1,2)However, resistance inevitably occurred after approximately 10 months of treatment.
基金supported by the National Key Research and Development Program of China(No.2022YFA1602200)the National Natural Science Foundation of China(Nos.12341501 and 12405174)the Hefei Comprehensive National Science Center for the strong support on the STCF key technology research project.
文摘Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy physics in the last two decades,a new-generation Tau-Charm factory,called the Super Tau-Charm Facility(STCF),has been actively promoted by the particle physics community in China.STCF has the potential to address fundamental questions such as the essence of color confinement and the matter-antimatter asymmetry within the next decades.The main design goals of the STCF are a center-of-mass energy ranging from 2 to 7 GeV and a luminosity surpassing 5×10^(34)cm^(−2)s^(−1)that is optimized at a center-of-mass energy of 4 GeV,which is approximately 50 times that of the currently operating Tau-Charm factory-BEPCII.The STCF accelerator has two main parts:a double-ring collider with a crab-waist collision scheme and an injector that provides top-up injections for both electron and positron beams.As a typical third-generation electron-positron circular collider,the STCF accelerator faces many challenges in both accelerator physics and technology.In this paper,the conceptual design of the STCF accelerator complex is presented,including the ongoing efforts and plans for technological research and develop-ment,as well as the required infrastructure.The STCF project aims to secure support from the Chinese central government for its construction during the 15th Five-Year Plan(2026-2030).
基金Supported by Open Project of Key Laboratory of Hubei Province(No.2023KFZZ026).
文摘AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55 eyes)with postoperative endophthalmitis were retrospectively included in this study with their medical records.Intraocular fluid samples were examined by NTS and microbial culture.All included patients had undergone examinations including measurement of best corrected visual acuity(BCVA)and intraocular pressure(IOP),slit-lamp biomicroscopy,and indirect ophthalmoscopy;additionally,they underwent B-ultrasound,anterior segment photography,and fundus photography if necessary.RESULTS:Among 55 patients with postoperative endophthalmitis,the age was 65.25±15.04y and there were 30 female(54.54%)patients.Forty-one(74.54%)vitreous humor samples and fourteen(25.45%)aqueous humor samples were sent for both NTS and microbial culture.NTS had a notable higher detection rate than microbial culture in detecting pathogens(90.91%vs 38.18%,χ^(2)=33.409,P<0.001).NTS exhibited high sensitivity of pathogen detection in both microbial culture positive and negative samples(100%and 85.29%,respectively).In 16 of 21(76.19%)patients who showed culture-positivity,their results corresponded with those of NTS.Moreover,in two patients(9.52%),NTS showed a better species resolution than microbial culture;in three patients(14.28%),NTS identified additional pathogens.As for fungus,the positive detection rate of NTS was significantly higher than that of microbial culture(20%vs 3.64%,χ^(2)=7.066,P=0.008).Also,NTS could detect multi-infection by bacteria and fungi than microbial culture(32.73%vs 0,χ^(2)=21.522,P<0.001).NTS could detect bacteria as well as fungi simultaneously within 48h in all patients.Meanwhile,NTS had a shorter detection time than microbial culture(1.13±0.34 vs 2.67±0.55d,Z=-9.218,P<0.001).After the NTS results were obtained,15 patients received additional intravitreal/intracameral anti-infection treatment.At follow-up,there was a statistically significant improvement in the visual acuity relative to the baseline(Z=−5.222,P<0.001).CONCLUSION:NTS can provide rapid identification and highly sensitive detection of pathogens among patients with postoperative endophthalmitis,which can guide anti-infection treatment and improve visual prognosis.
文摘In the history of bridge engineering, demand has always been the primary driving force for development. Driven by the huge demand for construction since China’s reform and opening-up, Chinese bridge has leapt forward both quantitatively and qualitatively in three major stages, by completing the transition from “follower” to “competitor,” and nally to “leader.” A new future is emerging for Chinese bridge engi- neering. As an important part of China’s transportation infrastructure, the bridge engineering industry is facing challenges in this new era on how to support the construction of a new form of transportation. This paper provides a summary of the status of bridge technology in China, based on a basic analysis of stock demand, incremental demand, and management demand. It is our belief that the Chinese bridge engi- neering industry must ful ll three outstanding requirements: construction ef ciency, management effec- tiveness, and long-term service. Intelligent technology based on information technology provides a new opportunity for innovation in bridge engineering. As a result, the development path of bridge engineering needs to be changed. This paper puts forward the idea of developing a third-generation bridge project that is characterized by intelligence, and discusses this project’s implications, development focus, and plan. In this way, this work provides a direction for the improvement of the core competitiveness of China’s bridge engineering industry.
基金supported by the National Key Research and Development Program of China(2022YFC2303401,2022YFC2304100,2016YFD0500301,2021YFC0863300)the Beijing Science and Technology Plan(Z211100002521017)the National Natural Science Foundation of China(82241080)。
文摘The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.
基金Supported by Research and Development Funding for Medical and Health Institutions,No.2021YL007.
文摘BACKGROUND Infectious diseases are still one of the greatest threats to human health,and the etiology of 20%of cases of clinical fever is unknown;therefore,rapid identification of pathogens is highly important.Traditional culture methods are only able to detect a limited number of pathogens and are time-consuming;serologic detection has window periods,false-positive and false-negative problems;and nucleic acid molecular detection methods can detect several known pathogens only once.Three-generation nanopore sequencing technology provides new options for identifying pathogens.CASE SUMMARY Case 1:The patient was admitted to the hospital with abdominal pain for three days and cessation of defecation for five days,accompanied by cough and sputum.Nanopore sequencing of the drainage fluid revealed the presence of orallike bacteria,leading to a clinical diagnosis of bronchopleural fistula.Cefoperazone sodium sulbactam treatment was effective.Case 2:The patient was admitted to the hospital with fever and headache,and CT revealed lung inflammation.Antibiotic treatment for Streptococcus pneumoniae,identified through nanopore sequencing of cerebrospinal fluid,was effective.Case 3:The patient was admitted to our hospital with intermittent fever and an enlarged neck mass that had persisted for more than six months.Despite antibacterial treatment,her symptoms worsened.The nanopore sequencing results indicate that voriconazole treatment is effective for Aspergillus brookii.The patient was diagnosed with mixed cell type classical Hodgkin's lymphoma with infection.CONCLUSION Three-generation nanopore sequencing technology allows for rapid and accurate detection of pathogens in human infectious diseases.
文摘A third-generation horseradish peroxidase (HRP) biosensor has been developed by adsorbing HRP on multi-wall carbon nanotube (MWNTs) monolayer modified gold electrode surface. The assembly process was investigated by electrochemical and spectroscopic techniques. Results showed that the immobilized HRP exhibited direct electrochemical behavior toward the reduction of H2O2. The resulting biosensor shows a fast amperometric response (<2 s) to H2O2. The linear response range was from 5.0×10-7～1.0×10-5 mol/L with a detection limit of 1.0×10-7mol/L. Moreover, the biosensor has a good reproducibility, and long-term stability.
基金Supported by China National University Student Innovation and Entrepreneurship Development Program(S202310553010)2023 Undergraduate Innovation and Entrepreneurship Training Program of Hunan University of Humanities,Science and Technology(14).
文摘[Objectives]This study was conducted to investigate the effects of adding compound probiotics on the growth performance and intestinal flora of Kunming mice.[Methods]Twelve healthy 2-week-old Kunming male mice with body weight of(11.09±0.43)g were selected.They were randomly divided into two treatment groups,namely blank control group(NC)and compound probiotics group(CB+LR+BS),with six mice in each group.The two groups were fed with commercial basal diet,and the compound probiotic experimental group was fed with basal diet supplemented with compound probiotics,in which the contents of Clostridium butyricum spores,Lactobacillus reuteri and Bacillus subtilis spores were 1×1010,1×1011 and 1×1010 CUF/kg,respectively.The body weight,feed intake and water intake of mice were counted every 4 d,and the experimental period was 13 d.On the 13 th day,the cecal contents of the mice were collected for analysis.[Results]There was no significant change in body weight and feed intake when compound probiotics were added to the diet.However,the addition of compound probiotics reduced the abundance of harmful bacteria such as Escherichia coli,urease-negative Helicobacter typhlonius and Salmonella enterica,while increasing the abundance of beneficial bacteria such as Anaerostipes hadrus,and the contents of IgG and IgM increased significantly(P<0.05).[Conclusions]In summary,the addition of compound probiotics could significantly improve the structure of intestinal microbial flora,increase the quantity of beneficial bacteria,reduce the quantity of harmful bacteria,and improve the immune function of mice.
基金supported by the institutional fund of the Department of Internal Medicine, University of Iowa, USA
文摘Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing （SGS） technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation （SV） in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with dis- eases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Addition- ally, PacBio＇s sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone.
