BACKGROUND:Post-cardiac arrest brain injury remains the leading cause of mortality and longterm disability in patients following cardiac arrest(CA).However,optimizing clinical management strategies for bundled therapy...BACKGROUND:Post-cardiac arrest brain injury remains the leading cause of mortality and longterm disability in patients following cardiac arrest(CA).However,optimizing clinical management strategies for bundled therapy after CA still faces challenges.METHODS:For this literature review,we searched PubMed,Web of Science,and SpringerLink databases for high-quality studies published between December 1982 and July 1,2024.The search included randomized clinical trials,meta-analyses,systematic reviews,and observational studies.References in included studies were also checked to identify additional sources.RESULTS:Many studies have identified potential targets for interventions to mitigate brain injury and improve outcomes for post-resuscitated patients.To optimize clinical management strategies to minimize brain injury after CA,we developed the acronym “SOOTEST-ICU” bundle,which includes “SOOTEST” therapy to optimize peripheral oxygen delivery and “ICU” intervention to optimize the cerebral oxygen cascade.The order of the “SOOTEST” treatment was organized based on the severity and importance of brain oxygen aff ecting brain injury.It includes systolic blood pressure and mean arterial pressure management,oxygenation and ventilation management,original etiological treatment,temperature control,electrolytes and acid basic status,seizure control,and targeted substrate delivery.The acronym “ICU” intervention includes intracerebral oxygen delivery,cerebral oxygen diff usion,and oxygen utilization.CONCLUSION:The “SOOTEST-ICU” therapy is developed to optimize oxygen and substrate cascades to minimize brain injury after CA.展开更多
A novel graft copolymer consisting of polyisoprene backbone and hydrophilic side chain with carbamic acid ester functional group was prepared via thiol-ene＂click＂reaction and alcohol-isocyanate reactions.Polyisopren...A novel graft copolymer consisting of polyisoprene backbone and hydrophilic side chain with carbamic acid ester functional group was prepared via thiol-ene＂click＂reaction and alcohol-isocyanate reactions.Polyisoprene was synthesized by anionic polymerization using n-butyl lithium as initiator,and the pendant hydroxyl groups were introduced by the thiol-ene reaction of mercaptoethanol with the double bond of 1,2-addition units of PI backbone in the presence of radical initiator azobisisobutyronitrile. Isocyanate end group capped poly（ethylene glycol）（mPEG-NCO） was grafted onto the PI backbone through alcoholisocyanate reaction between the pendant hydroxyl groups and isocyanate group of mPEG-NCO.The structure of the graft copolymer were characterized and confirmed by means of size-exclusion chromatography,~1H NMR and FTIR spectroscopy.展开更多
In marine engineering,appendages such as fin stabilizers and/or T-foils are made to rotate and to reduce the motion of ships.Research on the hydrodynamics of ships fitted with active appendages has significantly impro...In marine engineering,appendages such as fin stabilizers and/or T-foils are made to rotate and to reduce the motion of ships.Research on the hydrodynamics of ships fitted with active appendages has significantly improved the design and control of such ships.However,most studies focus on fixed rather than rotating appendages,thereby ignoring the hydrodynamic unsteadiness of active appendages.To enhance the reliability and precision of the numerical simulations,we propose the use of overlapping grids for simulating advanced catamarans fitted with a pair of rotating T-foils under each bow.The fundamental purpose of the overlapping grid technique is to realize information exchange via regional overlap sharing in each subdomain of the computing domain,instead of using the method of boundary sharing,thus greatly alleviating the difficulty of generating the subdomain grid;moreover,the technique guarantees the quality of the subdomain grid.Within the main computational domain,a subdomain was allocated to accommodate the T-foil.Overlapping meshes near the interface between the two domains enable information flow during the simulation;the overlapping grids are updated at every iteration step because the subdomain rotates.The instantaneous trim and sinkage responses of the catamaran to the T-foil rotation were reproduced.From the moment the active T-foil stopped moving,there was no change in the ship’s sailing attitude,indicating that the response was in real time.By comparing with EFD data,the numerical results showed reasonable agreement,indicating the feasibility and effectiveness of the technique in simulating the hydrodynamics of ships fitted with active appendages.展开更多
BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patie...BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patients diagnosed with HS,who were treated between May 1 and September 30,2018 at 15 tertiary hospitals from 11 cities in Northern China.RESULTS:Among the 175 patients,32 patients(18.29%)died before hospital discharge.After the univariate analysis,mechanical ventilation,initial mean arterial pressure<70 mmHg,maximum heart rate,lab results on day 1(white blood cell count,alanine aminotransferase,creatinine),and Glasgow admission prediction score were included in multivariate analysis.Multivariate Cox regression showed that invasive ventilation,initial mean arterial pressure<70 mmHg(1 mmHg=0.133 kPa),and Glasgow admission prediction score were independent risk factors for HS.The nomogram was established for predicting 7-d and 14-d survival in the training cohort.The nomogram exhibited a concordance index(C-index)of 0.880(95%confidence interval[95%CI]0.831-0.930)by bootstrapping validation(B=1,000).Furthermore,the nomogram performed better when predicting 14-d survival,compared to 7-d survival.The prognostic index cut-off value was set at 2.085,according to the operating characteristic curve for overall survival prediction.The model showed good calibration ability in the internal and external validation datasets.CONCLUSION:A novel nomogram,integrated with prognostic factors,was proposed;it was highly predictive of the survival in HS patients.展开更多
The host structure of polymers significantly influences ion transport and interfacial stability of electrolytes,dictating battery cycle life and safety for solid-state lithium metal batteries.Despite promising propert...The host structure of polymers significantly influences ion transport and interfacial stability of electrolytes,dictating battery cycle life and safety for solid-state lithium metal batteries.Despite promising properties of ethylene oxide-based electrolytes,their typical clamp-like coordination geometry leads to crowd solvation sheath and overly strong interactions between Li^(+)and electrolytes,rendering difficult dissociation of Li+and unfavorable solid electrolyte interface(SEI).Herein,we explore weakly solvating characteristics of polyacetal electrolytes owing to their alternately changing intervals between–O–coordinating sites in the main chain.Such structural asymmetry leads to unique distorted helical solvation sheath,and can effectively reduce Li^(+)-electrolyte binding and tune Li^(+)desolvation kinetics in the insitu formed polymer electrolytes,yielding anion-derived SEI and dendrite-free Li electrodeposition.Combining with photoinitiated cationic ring-opening polymerization,polyacetal electrolytes can be instantly formed within 5 min at the surface of electrode,with high segmental chain motion and well adapted interfaces.Such in-situ polyacetal electrolytes enabled more than 1300-h of stable lithium electrodeposition and prolonged cyclability over 200 cycles in solid-state batteries at ambient temperatures,demonstrating the vital role of molecular structure in changing solvating behavior and Li deposition stability for high-performance electrolytes.展开更多
Experiment of oxidation characteristics with slow velocity of high volatile blended coals was investigated in the surroundings of low oxygen conditions, which gives three kinetic factors in the step of low temperature...Experiment of oxidation characteristics with slow velocity of high volatile blended coals was investigated in the surroundings of low oxygen conditions, which gives three kinetic factors in the step of low temperature through the methods of thermo gravimetric analysis, the Coats-Redfern integration and Achar-Brindley-Sharp-Wendworth. The results of calculation show that activation energy and pre-exponential factor increase with the reaction process, and tendency of spontaneous combustion of the blended coal have changed. The experimental results show that the type of absorbing oxygen is mainly physical adsorption and calorific value is very small during increasing weight. Volatile of blended coal releases before single coal and combustion temperature of blended coal is between one and other single coals. If the oxygen content is below 16% in the milling system, explosion-proof effect on high volatile blended coal can be obtained.展开更多
1.Introduction.ecently,a study published in Nature Cancer by Shao et al.1 shows that intratumoral activation of the complement system promotes antitu-mor immunity and eliminates epidermal growth factor receptor(EGFR)-...1.Introduction.ecently,a study published in Nature Cancer by Shao et al.1 shows that intratumoral activation of the complement system promotes antitu-mor immunity and eliminates epidermal growth factor receptor(EGFR)-activated lung cancer resistance to immune-checkpoint inhibitor(ICI)treatment.This study unveiled the molecular and genetic mechanism underlying the EGFR-elicited intratumoral complement inhibition and provided a novel strategy to treat lung cancer with combination of ICIs and intratumoral complement system activation.展开更多
To simulate the dynamic responses of the multibody system with a floating base when the upper parts spread with a certain sequence and relative speed, the homogeneous matrix method is employed to model and simulate a ...To simulate the dynamic responses of the multibody system with a floating base when the upper parts spread with a certain sequence and relative speed, the homogeneous matrix method is employed to model and simulate a four-body system with a floating base and the motions are analyzed when the upper parts are spread sequentially or synchronously. The rolling, swaying and heaving temporal variations are obtained when the multibody system is under the conditions of the static water along with the wave loads and the mean wind loads or the single pulse wind loads, respectively. The moment variations of each joint under the single pulse wind load are also gained. The numerical results showed that the swaying of the floating base is almost not influenced by the spreading time or form when the upper parts spread sequentially or synchronously, while the rolling and the heaving mainly depend on the spreading time and forms. The swaying and heaving motions are influenced significantly by the mean wind loads. The single pulse wind load also has influences on the dynamic responses. The torque of joint 3 and joint 4 in the single pulse wind environment may be twice that in the windless environment when the system spreads with 60 s duration.展开更多
1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symp...1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].展开更多
Microstructure of W-Cu alloy wire before and after hot-swaging was studied in this paper. Results show that a homogeneous microstructure of the W-Cu alloy wire was formed after hot-swaging treatment, and the tungsten ...Microstructure of W-Cu alloy wire before and after hot-swaging was studied in this paper. Results show that a homogeneous microstructure of the W-Cu alloy wire was formed after hot-swaging treatment, and the tungsten particles were embedded in copper phases to form a networking structure;the W-Cu alloy wire has a microstructure of body-centered-cubic tungsten particles and face-centered-cubic copper phase, and did not change after hot-swaging. The intermediate phases have not been found during the process, but the size of the tungsten particles in the copper matrix becomes smaller. After hot-swaging, the treated W-Cu alloy wire has a relative density of 105.1%, and a conductivity of 47.2% IACS, the tensile and bending strength can be as large as 644 and 1600 MPa, respectively.展开更多
The route of vaccine administration is associated with various immune outcomes,and the relationship between the route of administration and broad protection against heterologous pathogens remains unclear.Here,we found...The route of vaccine administration is associated with various immune outcomes,and the relationship between the route of administration and broad protection against heterologous pathogens remains unclear.Here,we found that subcutaneous vaccination with Bacillus Calmette-Guérin(BCG)promotes respiratory influenza clearance and T-cell responses.Group 1 innate lymphoid cells(ILC1s)express MHCII molecules and engage in antigen processing and presentation after BCG vaccination.During influenza virus infection,ILC1s in the lungs of BCG-vaccinated mice can present influenza virus antigens and prime Th1 cells.After subcutaneous vaccination with BCG,MHCII^(+)ILC1s migrate from the skin to the lungs and play an antigen-presenting role in influenza infection.Both the BCG and the BCG component lipomannan can induce MHCII expression and skin-to-lung migration of ILC1s via TLR2 signaling.Our study revealed an important regulatory mechanism by which subcutaneous vaccination with BCG promotes respiratory antiviral immune responses via the skin‒lung axis.展开更多
Infectious diseases such as coronavirus disease 2019(COVID-19)continue to pose significant global health challenges.Effective management of reinfection risks depends on sustained levels of binding and neutralizing ant...Infectious diseases such as coronavirus disease 2019(COVID-19)continue to pose significant global health challenges.Effective management of reinfection risks depends on sustained levels of binding and neutralizing antibodies.However,conventional methods—such as enzyme-linked immunosorbent assays(ELISA)and virus neutralization tests(VNT)—are limited by complex workflows,long assay durations,and high sample volume requirements,making them less suit-able for routine,decentralized,or time-sensitive surveillance.This study presents a custom-developed tip optofluidic immunoassay(TOI)platform that enables rapid,multiplexed antibody profiling using only 1 mL offingertip blood.The system integrates batch-fabricated microfluidic immunoreactors with a portable chemiluminescent imaging station,completing both binding and neutralization capability assessments within 40 min.TOI achieves a broad dynamic range(3–4 orders of magnitude),high signal-to-noise ratio(10,000),and excellent sensitivity for immunoglobulin G(IgG)detection.A renovated version of the rapid in vitro inhibition assay(RIVIA)is incorporated to evaluate neutralizing an-tibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with greater speed and cost-effi-ciency.In clinical studies,TOI successfully quantified antibody protection against multiple variants,identifying individ-uals with broad-spectrum immunity to both wild-type and XBB strains.With its high-precision,rapid turnaround,and minimal sample requirement,TOI offers a valuable tool for decentralized immune surveillance and personalized immu-nization strategy development.展开更多
Understanding the habitat shifting pattern is a prerequisite for implementing in situ conservation of migratory species.Spotted seals(Phoca largha)inhabiting the Yellow Sea ecoregion(YSE)comprise a small population wi...Understanding the habitat shifting pattern is a prerequisite for implementing in situ conservation of migratory species.Spotted seals(Phoca largha)inhabiting the Yellow Sea ecoregion(YSE)comprise a small population with independent genes and represent a charismatic flagship species in this region.However,this population has declined by 80%since the 1940s,and increased support from the countries around the YSE is urgently needed to address the potential local extinction risk.A time-series niche model and life-history weighted systematic conservation planning were designed on the basis of a satellite beacon tracking survey(2010–2020)of the YSE population.The results showed clustering and spreading shifting patterns during the breeding and migratory seasons,respectively.The closed-loop migration route formed in the YSE indicated that this population might be geographically isolated from populations in other breeding areas around the world.The conservation priority area(CPA),with an area of 19632 km^(2)(3.58%of the total YSE area),was the most effective response to the potential in situ risk.However,nearly 80%of the CPA was exposed outside the existing marine protected areas(MPAs).Future establishment of MPAs in China should strategically consider the conservation gap identified herein,and it is recommended for Korea’s closed fishing season to be spatially set in the western Korean Peninsula from May to August.This study also exemplified that the lack of temporal information would lead to the dislocation of niche modeling for migratory species represented by spotted seals.Attention should be paid to protecting small and migratory populations in marine biodiversity conservation planning.展开更多
Various vaccine technologies have been employed in the coronavirus disease 2019(COVID-19)vaccines,including whole inactivated virus(WIV),recombinant protein,mRNA,and nanoparticle vaccines.To elucidate the cellular mec...Various vaccine technologies have been employed in the coronavirus disease 2019(COVID-19)vaccines,including whole inactivated virus(WIV),recombinant protein,mRNA,and nanoparticle vaccines.To elucidate the cellular mechanisms underlying the immune responses elicited by different vaccines,we examined and compared antigen-specific B cell responses targeting the receptor-binding domain(RBD)of the viral spike protein.We found that the nanoparticle vaccine pathogen-like antigens-RBD(PLA-RBD)and the mRNA vaccine demonstrated superior immunogenicity compared with the WIV vaccine and the RBD-dimer,a recombinant protein vaccine.Interestingly,the WIV vaccine contains toll-like receptor ligands that enhance IgG2a/c class-switching.For the mRNA vaccine,although it induces robust germinal center responses and T follicular helper(Tfh)cells,it has limited ability to induce memory B cells and long-lived plasma cells.These results indicate that vaccine formats significantly influence both the quantity and quality of immune responses,providing valuable insights for the future development of vaccines.展开更多
Simultaneous Localization and Mapping(SLAM)is the process by which a mobile robot can build a map of the surrounding environment and compute its own location.Feature point extraction is one of the key components of a ...Simultaneous Localization and Mapping(SLAM)is the process by which a mobile robot can build a map of the surrounding environment and compute its own location.Feature point extraction is one of the key components of a SLAM system.The extraction accuracy and efficiency of corner detection directly affect the overall accuracy and throughput of the system.However,the complexity of corner detection algorithms makes it challenging to achieve real-time implementation and efficient,low-cost hardware design,especially for mobile robots.Harris corner detection class algorithms including Harris and GFTT(Good Feature to Track)have improved accuracy.However,those algorithms require high resource consumption and latency when implemented on hardware platforms.The GFTT achieves higher accuracy than Harris while requiring higher computational complexity.To address the throughput problem,SFTT(Simple Feature to Track),a new Harris class detection algorithm is proposed,and the corresponding hardware accelerator is designed.The proposed SFTT significantly reduced the computational complexity compared with the Harris algorithm and GFTT.Experiments have shown SFTT also achieved slightly higher accuracy compared with the two algorithms.Furthermore,the GFTT accelerator is designed which reaches up to 325 fps at the frequency of 100 MHz.The proposed design has achieved an improvement in throughput by 1.3×times and power efficiency by 1.7×times as compared to state-of-the-art design.展开更多
Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)...Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor progression.However,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely unclear.In this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.Methods:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts.CSC-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model.Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133.The expression levels of CD133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry assay.RNA expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription PCR.Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay.CD133+cells were sorted by flow cytometry using an anti-CD133 antibody.Results:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts.HK2 depletion inhibited CSC stemness and promoted CSC differentiation.Mechanistically,nonmitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels.The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to CD133,thereby inhibiting CD133 polyubiquitylation and degradation.HK2-mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators,SCLC cell stemness,and tumor growth in mice.In addition,HK2 expression was positively correlated with CD133 expression in human SCLC specimens,and their expression levels were associated with poor prognosis of SCLC patients.Conclusions:These results revealed a critical non-metabolic function of HK2 in promotion of cancer cell stemness.Our findings provided new insights into the multifaceted roles of HK2 in tumor development.展开更多
Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the...Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.展开更多
The mucosal immune system is considered a local immune system,a term that implies regional restriction.Mucosal tissues are continually exposed to a wide range of antigens.The regulation of mucosal immune cells is tigh...The mucosal immune system is considered a local immune system,a term that implies regional restriction.Mucosal tissues are continually exposed to a wide range of antigens.The regulation of mucosal immune cells is tightly associated with the progression of mucosal diseases.Innate lymphoid cells(ILCs)are abundant in mucosal barriers and serve as first-line defenses against pathogens.The subtype changes and translocation of ILCs are accompanied by the pathologic processes of mucosal diseases.Here,we review the plasticity and circulation of ILCs in the mucosal immune system under physiological and pathological conditions.We also discuss the signaling pathways involved in dynamic ILC changes and the related targets in mucosal diseases.展开更多
To the Editor:Cardiac arrest(CA)is the leading cause of morbidity and mortality among hospitalized patients globally and has low rates of overall survival.After the return of spontaneous circulation(ROSC),patients wit...To the Editor:Cardiac arrest(CA)is the leading cause of morbidity and mortality among hospitalized patients globally and has low rates of overall survival.After the return of spontaneous circulation(ROSC),patients with CA and systemic ischemia/reperfusion injury can manifest as sepsis-like syndromes and immune disorders that increase the risk of infections.CD4^(+)T lymphocytes play an important role in organ ischemia-reperfusion injury.T-helper(Th)types 1 and 2 cells are classical subsets of CD4^(+)T cells.Extensive research on their functions in infectious and immune-related inflammatory diseases indicates that both subsets participate in host defense and direct immune responses.Data from CA/cardiopulmonary resuscitation porcine models and patients have revealed imbalances in Th1/Th2 cell ratio.[1]Therefore,Th1 and Th2 cells are important for understanding post-ROSC immune dysfunction in patients with CA.展开更多
基金supported by the High-Level Public Health Technical Talent Building Program (Discipline Leader-01-01)Capital’s Funds for Health Improvement and Research (CFH 2022-1-2032)+1 种基金National Natural Science Foundation of China (82072136)Beijing Hospitals Authority’s Ascent Plan (DFL20240302)。
文摘BACKGROUND:Post-cardiac arrest brain injury remains the leading cause of mortality and longterm disability in patients following cardiac arrest(CA).However,optimizing clinical management strategies for bundled therapy after CA still faces challenges.METHODS:For this literature review,we searched PubMed,Web of Science,and SpringerLink databases for high-quality studies published between December 1982 and July 1,2024.The search included randomized clinical trials,meta-analyses,systematic reviews,and observational studies.References in included studies were also checked to identify additional sources.RESULTS:Many studies have identified potential targets for interventions to mitigate brain injury and improve outcomes for post-resuscitated patients.To optimize clinical management strategies to minimize brain injury after CA,we developed the acronym “SOOTEST-ICU” bundle,which includes “SOOTEST” therapy to optimize peripheral oxygen delivery and “ICU” intervention to optimize the cerebral oxygen cascade.The order of the “SOOTEST” treatment was organized based on the severity and importance of brain oxygen aff ecting brain injury.It includes systolic blood pressure and mean arterial pressure management,oxygenation and ventilation management,original etiological treatment,temperature control,electrolytes and acid basic status,seizure control,and targeted substrate delivery.The acronym “ICU” intervention includes intracerebral oxygen delivery,cerebral oxygen diff usion,and oxygen utilization.CONCLUSION:The “SOOTEST-ICU” therapy is developed to optimize oxygen and substrate cascades to minimize brain injury after CA.
基金supports of the Special Funds for Major Basic Research Projects (NoG2011CB606001)Zhejiang Provincial Top Key Discipline of New Materials and Process Engineering(No 20110926)
文摘A novel graft copolymer consisting of polyisoprene backbone and hydrophilic side chain with carbamic acid ester functional group was prepared via thiol-ene＂click＂reaction and alcohol-isocyanate reactions.Polyisoprene was synthesized by anionic polymerization using n-butyl lithium as initiator,and the pendant hydroxyl groups were introduced by the thiol-ene reaction of mercaptoethanol with the double bond of 1,2-addition units of PI backbone in the presence of radical initiator azobisisobutyronitrile. Isocyanate end group capped poly（ethylene glycol）（mPEG-NCO） was grafted onto the PI backbone through alcoholisocyanate reaction between the pendant hydroxyl groups and isocyanate group of mPEG-NCO.The structure of the graft copolymer were characterized and confirmed by means of size-exclusion chromatography,~1H NMR and FTIR spectroscopy.
基金Supported by the National Natural Science Foundation of China(Grant No.51509053)
文摘In marine engineering,appendages such as fin stabilizers and/or T-foils are made to rotate and to reduce the motion of ships.Research on the hydrodynamics of ships fitted with active appendages has significantly improved the design and control of such ships.However,most studies focus on fixed rather than rotating appendages,thereby ignoring the hydrodynamic unsteadiness of active appendages.To enhance the reliability and precision of the numerical simulations,we propose the use of overlapping grids for simulating advanced catamarans fitted with a pair of rotating T-foils under each bow.The fundamental purpose of the overlapping grid technique is to realize information exchange via regional overlap sharing in each subdomain of the computing domain,instead of using the method of boundary sharing,thus greatly alleviating the difficulty of generating the subdomain grid;moreover,the technique guarantees the quality of the subdomain grid.Within the main computational domain,a subdomain was allocated to accommodate the T-foil.Overlapping meshes near the interface between the two domains enable information flow during the simulation;the overlapping grids are updated at every iteration step because the subdomain rotates.The instantaneous trim and sinkage responses of the catamaran to the T-foil rotation were reproduced.From the moment the active T-foil stopped moving,there was no change in the ship’s sailing attitude,indicating that the response was in real time.By comparing with EFD data,the numerical results showed reasonable agreement,indicating the feasibility and effectiveness of the technique in simulating the hydrodynamics of ships fitted with active appendages.
文摘BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patients diagnosed with HS,who were treated between May 1 and September 30,2018 at 15 tertiary hospitals from 11 cities in Northern China.RESULTS:Among the 175 patients,32 patients(18.29%)died before hospital discharge.After the univariate analysis,mechanical ventilation,initial mean arterial pressure<70 mmHg,maximum heart rate,lab results on day 1(white blood cell count,alanine aminotransferase,creatinine),and Glasgow admission prediction score were included in multivariate analysis.Multivariate Cox regression showed that invasive ventilation,initial mean arterial pressure<70 mmHg(1 mmHg=0.133 kPa),and Glasgow admission prediction score were independent risk factors for HS.The nomogram was established for predicting 7-d and 14-d survival in the training cohort.The nomogram exhibited a concordance index(C-index)of 0.880(95%confidence interval[95%CI]0.831-0.930)by bootstrapping validation(B=1,000).Furthermore,the nomogram performed better when predicting 14-d survival,compared to 7-d survival.The prognostic index cut-off value was set at 2.085,according to the operating characteristic curve for overall survival prediction.The model showed good calibration ability in the internal and external validation datasets.CONCLUSION:A novel nomogram,integrated with prognostic factors,was proposed;it was highly predictive of the survival in HS patients.
基金financially supported by National Natural Science Foundation of China(52003231,22065037)Yunnan Fundamental Research Projects(202201AW070015)。
文摘The host structure of polymers significantly influences ion transport and interfacial stability of electrolytes,dictating battery cycle life and safety for solid-state lithium metal batteries.Despite promising properties of ethylene oxide-based electrolytes,their typical clamp-like coordination geometry leads to crowd solvation sheath and overly strong interactions between Li^(+)and electrolytes,rendering difficult dissociation of Li+and unfavorable solid electrolyte interface(SEI).Herein,we explore weakly solvating characteristics of polyacetal electrolytes owing to their alternately changing intervals between–O–coordinating sites in the main chain.Such structural asymmetry leads to unique distorted helical solvation sheath,and can effectively reduce Li^(+)-electrolyte binding and tune Li^(+)desolvation kinetics in the insitu formed polymer electrolytes,yielding anion-derived SEI and dendrite-free Li electrodeposition.Combining with photoinitiated cationic ring-opening polymerization,polyacetal electrolytes can be instantly formed within 5 min at the surface of electrode,with high segmental chain motion and well adapted interfaces.Such in-situ polyacetal electrolytes enabled more than 1300-h of stable lithium electrodeposition and prolonged cyclability over 200 cycles in solid-state batteries at ambient temperatures,demonstrating the vital role of molecular structure in changing solvating behavior and Li deposition stability for high-performance electrolytes.
文摘Experiment of oxidation characteristics with slow velocity of high volatile blended coals was investigated in the surroundings of low oxygen conditions, which gives three kinetic factors in the step of low temperature through the methods of thermo gravimetric analysis, the Coats-Redfern integration and Achar-Brindley-Sharp-Wendworth. The results of calculation show that activation energy and pre-exponential factor increase with the reaction process, and tendency of spontaneous combustion of the blended coal have changed. The experimental results show that the type of absorbing oxygen is mainly physical adsorption and calorific value is very small during increasing weight. Volatile of blended coal releases before single coal and combustion temperature of blended coal is between one and other single coals. If the oxygen content is below 16% in the milling system, explosion-proof effect on high volatile blended coal can be obtained.
基金supported by National Key R&D Program of China(grant numbers:2020YFA0803300,2020AAA0109500)National Natural Science Foundation of China(grant numbers:82188102,82030074,82122053,32100574)+1 种基金Zhejiang Natural Science Foundation-Key Project(grant number:LD21H160003)Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(grant number:2019R01001).
文摘1.Introduction.ecently,a study published in Nature Cancer by Shao et al.1 shows that intratumoral activation of the complement system promotes antitu-mor immunity and eliminates epidermal growth factor receptor(EGFR)-activated lung cancer resistance to immune-checkpoint inhibitor(ICI)treatment.This study unveiled the molecular and genetic mechanism underlying the EGFR-elicited intratumoral complement inhibition and provided a novel strategy to treat lung cancer with combination of ICIs and intratumoral complement system activation.
基金the National Natural Science Foundation of China，Major State Basic Research Development Program of China （973 Program）
文摘To simulate the dynamic responses of the multibody system with a floating base when the upper parts spread with a certain sequence and relative speed, the homogeneous matrix method is employed to model and simulate a four-body system with a floating base and the motions are analyzed when the upper parts are spread sequentially or synchronously. The rolling, swaying and heaving temporal variations are obtained when the multibody system is under the conditions of the static water along with the wave loads and the mean wind loads or the single pulse wind loads, respectively. The moment variations of each joint under the single pulse wind load are also gained. The numerical results showed that the swaying of the floating base is almost not influenced by the spreading time or form when the upper parts spread sequentially or synchronously, while the rolling and the heaving mainly depend on the spreading time and forms. The swaying and heaving motions are influenced significantly by the mean wind loads. The single pulse wind load also has influences on the dynamic responses. The torque of joint 3 and joint 4 in the single pulse wind environment may be twice that in the windless environment when the system spreads with 60 s duration.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(No.2019-I2M-5-023)Hainan Provincial Science and Technology Major Project(No.ZDKJ201804)+2 种基金National Natural Science Foundation of China(No.81871611)National Natural Science Foundation of China(No.81760352)Project of Hainan Provincial Department of Education(No.Hnjg2019ZD-16)
文摘1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].
文摘Microstructure of W-Cu alloy wire before and after hot-swaging was studied in this paper. Results show that a homogeneous microstructure of the W-Cu alloy wire was formed after hot-swaging treatment, and the tungsten particles were embedded in copper phases to form a networking structure;the W-Cu alloy wire has a microstructure of body-centered-cubic tungsten particles and face-centered-cubic copper phase, and did not change after hot-swaging. The intermediate phases have not been found during the process, but the size of the tungsten particles in the copper matrix becomes smaller. After hot-swaging, the treated W-Cu alloy wire has a relative density of 105.1%, and a conductivity of 47.2% IACS, the tensile and bending strength can be as large as 644 and 1600 MPa, respectively.
基金supported by the National Key R&D Program of China(2022YFC2302900,2021YFA1300202,2023YFC2306204)the Beijing Natural Science Foundation(JQ24043)the CAS Project for Young Scientists in Basic Research(YSBR-010).
文摘The route of vaccine administration is associated with various immune outcomes,and the relationship between the route of administration and broad protection against heterologous pathogens remains unclear.Here,we found that subcutaneous vaccination with Bacillus Calmette-Guérin(BCG)promotes respiratory influenza clearance and T-cell responses.Group 1 innate lymphoid cells(ILC1s)express MHCII molecules and engage in antigen processing and presentation after BCG vaccination.During influenza virus infection,ILC1s in the lungs of BCG-vaccinated mice can present influenza virus antigens and prime Th1 cells.After subcutaneous vaccination with BCG,MHCII^(+)ILC1s migrate from the skin to the lungs and play an antigen-presenting role in influenza infection.Both the BCG and the BCG component lipomannan can induce MHCII expression and skin-to-lung migration of ILC1s via TLR2 signaling.Our study revealed an important regulatory mechanism by which subcutaneous vaccination with BCG promotes respiratory antiviral immune responses via the skin‒lung axis.
基金supported by the Outstanding Young Innovator Fund,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences(to X.T.)the State Key Laboratory of Biomedical Imaging Science and System+5 种基金Shenzhen Basic Research Project of Natural Science Foundation(JCYJ20230808105701004 to Y.C.)Shenzhen Science and Technology Innovations Committee(JSGGZD20220822095200001 to H.Y.)National Science Foundation of China(32270937 to F.Y.)Ministry of Science and Technology of China(2021D0102 to Y.C.)Guangdong Basic and Applied Basic Research Foundation(2025A1515012136 to H.L.)Medicine Plus Program of Shenzhen University(2024YG015 to Y.C.).
文摘Infectious diseases such as coronavirus disease 2019(COVID-19)continue to pose significant global health challenges.Effective management of reinfection risks depends on sustained levels of binding and neutralizing antibodies.However,conventional methods—such as enzyme-linked immunosorbent assays(ELISA)and virus neutralization tests(VNT)—are limited by complex workflows,long assay durations,and high sample volume requirements,making them less suit-able for routine,decentralized,or time-sensitive surveillance.This study presents a custom-developed tip optofluidic immunoassay(TOI)platform that enables rapid,multiplexed antibody profiling using only 1 mL offingertip blood.The system integrates batch-fabricated microfluidic immunoreactors with a portable chemiluminescent imaging station,completing both binding and neutralization capability assessments within 40 min.TOI achieves a broad dynamic range(3–4 orders of magnitude),high signal-to-noise ratio(10,000),and excellent sensitivity for immunoglobulin G(IgG)detection.A renovated version of the rapid in vitro inhibition assay(RIVIA)is incorporated to evaluate neutralizing an-tibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with greater speed and cost-effi-ciency.In clinical studies,TOI successfully quantified antibody protection against multiple variants,identifying individ-uals with broad-spectrum immunity to both wild-type and XBB strains.With its high-precision,rapid turnaround,and minimal sample requirement,TOI offers a valuable tool for decentralized immune surveillance and personalized immu-nization strategy development.
基金This study was funded by the National Key R&D Program of China(2022YFF0802204)the National Natural Science Foundation of China(grant no.32201433)+1 种基金World Wildlife Fund(project code:Ocean-A000588)the National Key R&D Program of China(2018YFD0900806).
文摘Understanding the habitat shifting pattern is a prerequisite for implementing in situ conservation of migratory species.Spotted seals(Phoca largha)inhabiting the Yellow Sea ecoregion(YSE)comprise a small population with independent genes and represent a charismatic flagship species in this region.However,this population has declined by 80%since the 1940s,and increased support from the countries around the YSE is urgently needed to address the potential local extinction risk.A time-series niche model and life-history weighted systematic conservation planning were designed on the basis of a satellite beacon tracking survey(2010–2020)of the YSE population.The results showed clustering and spreading shifting patterns during the breeding and migratory seasons,respectively.The closed-loop migration route formed in the YSE indicated that this population might be geographically isolated from populations in other breeding areas around the world.The conservation priority area(CPA),with an area of 19632 km^(2)(3.58%of the total YSE area),was the most effective response to the potential in situ risk.However,nearly 80%of the CPA was exposed outside the existing marine protected areas(MPAs).Future establishment of MPAs in China should strategically consider the conservation gap identified herein,and it is recommended for Korea’s closed fishing season to be spatially set in the western Korean Peninsula from May to August.This study also exemplified that the lack of temporal information would lead to the dislocation of niche modeling for migratory species represented by spotted seals.Attention should be paid to protecting small and migratory populations in marine biodiversity conservation planning.
基金approved by the Animal Care and Use Committee of the Institute of Biophysics,Chinese Academy of Sciences(SYXK2023171,SYXK2019012).
文摘Various vaccine technologies have been employed in the coronavirus disease 2019(COVID-19)vaccines,including whole inactivated virus(WIV),recombinant protein,mRNA,and nanoparticle vaccines.To elucidate the cellular mechanisms underlying the immune responses elicited by different vaccines,we examined and compared antigen-specific B cell responses targeting the receptor-binding domain(RBD)of the viral spike protein.We found that the nanoparticle vaccine pathogen-like antigens-RBD(PLA-RBD)and the mRNA vaccine demonstrated superior immunogenicity compared with the WIV vaccine and the RBD-dimer,a recombinant protein vaccine.Interestingly,the WIV vaccine contains toll-like receptor ligands that enhance IgG2a/c class-switching.For the mRNA vaccine,although it induces robust germinal center responses and T follicular helper(Tfh)cells,it has limited ability to induce memory B cells and long-lived plasma cells.These results indicate that vaccine formats significantly influence both the quantity and quality of immune responses,providing valuable insights for the future development of vaccines.
基金supported by the National Natural Science Foundation of China under Grant U20A20220.
文摘Simultaneous Localization and Mapping(SLAM)is the process by which a mobile robot can build a map of the surrounding environment and compute its own location.Feature point extraction is one of the key components of a SLAM system.The extraction accuracy and efficiency of corner detection directly affect the overall accuracy and throughput of the system.However,the complexity of corner detection algorithms makes it challenging to achieve real-time implementation and efficient,low-cost hardware design,especially for mobile robots.Harris corner detection class algorithms including Harris and GFTT(Good Feature to Track)have improved accuracy.However,those algorithms require high resource consumption and latency when implemented on hardware platforms.The GFTT achieves higher accuracy than Harris while requiring higher computational complexity.To address the throughput problem,SFTT(Simple Feature to Track),a new Harris class detection algorithm is proposed,and the corresponding hardware accelerator is designed.The proposed SFTT significantly reduced the computational complexity compared with the Harris algorithm and GFTT.Experiments have shown SFTT also achieved slightly higher accuracy compared with the two algorithms.Furthermore,the GFTT accelerator is designed which reaches up to 325 fps at the frequency of 100 MHz.The proposed design has achieved an improvement in throughput by 1.3×times and power efficiency by 1.7×times as compared to state-of-the-art design.
基金Ministry of Science and Technology of the People’s Republic of China,Grant/Award Number:2020YFA0803300National Natural Science Foundation of China,Grant/Award Numbers:82188102,82030074,82122053,32100574+10 种基金Beijing Municipal Science&Technology Commission,Grant/Award Number:Z191100006619115R&D Program of Beijing Municipal Education commission,Grant/Award Number:KJZD20191002302CAMS Innovation Fund for Medical Science,Grant/Award Numbers:2021-1-I2M-012,2021-I2M-1-067Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2021-PT310-001Key-Area Research and Development Program of Guangdong Province,Grant/Award Number:2021B0101420005Sanming Project of Medicine in Shenzhen,Grant/Award Numbers:SZSM201612097,SZSM201812062Aiyou Foundation,Grant/Award Number:KY201701Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2020QH191Zhejiang Natural Science Foundation-Key Project,Grant/Award Number:LD21H160003Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang,Grant/Award Number:2019R01001Zhimin Lu is the Kuancheng Wang Distinguished Chair。
文摘Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor progression.However,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely unclear.In this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.Methods:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts.CSC-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model.Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133.The expression levels of CD133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry assay.RNA expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription PCR.Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay.CD133+cells were sorted by flow cytometry using an anti-CD133 antibody.Results:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts.HK2 depletion inhibited CSC stemness and promoted CSC differentiation.Mechanistically,nonmitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels.The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to CD133,thereby inhibiting CD133 polyubiquitylation and degradation.HK2-mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators,SCLC cell stemness,and tumor growth in mice.In addition,HK2 expression was positively correlated with CD133 expression in human SCLC specimens,and their expression levels were associated with poor prognosis of SCLC patients.Conclusions:These results revealed a critical non-metabolic function of HK2 in promotion of cancer cell stemness.Our findings provided new insights into the multifaceted roles of HK2 in tumor development.
基金This study was funded by The National Key R&D Program of China(2017YFC1308702,2017YFC1311000,2018YFC1312100)the Beijing Municipal Science&Technology Commission(Z181100006218032,Z181100001918002)+1 种基金the CAMS Initiative for Innovative Medicine(2017-I2M-1-005,2017-I2M-2-003,2019-I2M-2-002)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2017PT32001,2017PT32017).
文摘Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.
基金supported by the National Natural Science Foundation of China(92169113)the CAS Project for Young Scientists in Basic Research(YSBR-010)+1 种基金the National Key R&D Program of China(2022YFC2302900)the Key Research Program of Frontier Sciences of CAS(ZDBS-LY-SM025)。
基金supported by the Strategic Priority Research Programs of the Chinese Academy of Sciences(XDB29020000)the National Natural Science Foundation of China(81722023,81922031)+2 种基金the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences(ZDBS-LY-SM025)the Beijing Natural Science Foundation(7212067)the Youth Innovation Promotion Association of CAS to S.W.
文摘The mucosal immune system is considered a local immune system,a term that implies regional restriction.Mucosal tissues are continually exposed to a wide range of antigens.The regulation of mucosal immune cells is tightly associated with the progression of mucosal diseases.Innate lymphoid cells(ILCs)are abundant in mucosal barriers and serve as first-line defenses against pathogens.The subtype changes and translocation of ILCs are accompanied by the pathologic processes of mucosal diseases.Here,we review the plasticity and circulation of ILCs in the mucosal immune system under physiological and pathological conditions.We also discuss the signaling pathways involved in dynamic ILC changes and the related targets in mucosal diseases.
文摘To the Editor:Cardiac arrest(CA)is the leading cause of morbidity and mortality among hospitalized patients globally and has low rates of overall survival.After the return of spontaneous circulation(ROSC),patients with CA and systemic ischemia/reperfusion injury can manifest as sepsis-like syndromes and immune disorders that increase the risk of infections.CD4^(+)T lymphocytes play an important role in organ ischemia-reperfusion injury.T-helper(Th)types 1 and 2 cells are classical subsets of CD4^(+)T cells.Extensive research on their functions in infectious and immune-related inflammatory diseases indicates that both subsets participate in host defense and direct immune responses.Data from CA/cardiopulmonary resuscitation porcine models and patients have revealed imbalances in Th1/Th2 cell ratio.[1]Therefore,Th1 and Th2 cells are important for understanding post-ROSC immune dysfunction in patients with CA.
