Experimental validation of laser intensity is particularly important for the study of fundamental physics at extremely high intensities.However,reliable diagnosis of the focal spot and peak intensity faces huge challe...Experimental validation of laser intensity is particularly important for the study of fundamental physics at extremely high intensities.However,reliable diagnosis of the focal spot and peak intensity faces huge challenges.In this work,we demonstrate for the firs time that the coherent radiation farfiel patterns from laser–foil interactions can serve as an in situ,real-time,and easy-to-implement diagnostic for an ultraintense laser focus.The laser-driven electron sheets,curved by the spatially varying laser fiel and leaving the targets at nearly the speed of light,produce doughnut-shaped patterns depending on the shapes of the focal spot and the absolute laser intensities.Assisted by particle-in-cell simulations,we can achieve measurements of the intensity and the focal spot,and provide immediate feedback to optimize the focal spots for extremely high intensity.展开更多
BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC...BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC)lesions,they are benign.As such,it is important to develop methods to distinguish between FNH-like lesions and HCC.AIM To evaluate diagnostically differential radiological findings between FNH-like lesions and HCC.METHODS We studied pathologically confirmed FNH-like lesions in 13 patients with alco-holic cirrhosis[10 men and 3 women;mean age:54.5±12.5(33-72)years]who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography(CT)and magnetic resonance imaging(MRI),including superparamagnetic iron oxide(SPIO)and/or gadoxetic acid-enhanced MRI.Seven patients also underwent angiography-assisted CT.RESULTS The evaluated lesion features included arterial enhancement pattern,washout appearance(low density compared with that of surrounding liver parenchyma),signal intensity on T1-weighted image(T1WI)and T2-weighted image(T2WI),central scar presence,chemical shift on in-and out-of-phase images,and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and SPIO-enhanced MRI.Eleven patients had multiple small lesions(<1.5 cm).Radiological features of FNH-like lesions included hypervascularity despite small lesions,lack of“corona-like”enhancement in the late phase on CT during hepatic angiography(CTHA),high-intensity on T1WI,slightly high-or iso-intensity on T2WI,no signal decrease in out-of-phase images,and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid.Pathologically,similar to HCC,FNH-like lesions showed many unpaired arteries and sinusoidal capillarization.CONCLUSION Overall,the present study showed that FNH-like lesions have unique radiological findings useful for differential diagnosis.Specifically,SPIO-and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.展开更多
BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progr...BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.展开更多
We report an interesting and abnormal electromagnetic phenomenon with regard to a terajet(TJ)that is generated in a reflection mode,which is realized by placing a dielectric scatterer onto a metal reflection plate.We ...We report an interesting and abnormal electromagnetic phenomenon with regard to a terajet(TJ)that is generated in a reflection mode,which is realized by placing a dielectric scatterer onto a metal reflection plate.We show that the introduction of an air hollow into metal reflection plate beneath the scatterer does not induce an expected decrease but an abnormal increase of focal length of the TJ by as much as more than three times.This abnormal phenomenon takes place in case that the air hollow is shallow and there exists a critical hollow depth for a given lateral size of air hollow.Larger than the critical depth,the phenomenon no longer occurs.It is explained from viewpoints of both ray optics in terms of role of relative portion of central waves in TJ formation and electromagnetic field theory with regard to hollow-induced phase singularities.展开更多
Objective:Focal therapy(FT)is a potential treatment option for limited-volume clinically-significant prostate cancer(csPCa).However,despite rigorous selection,approximately 20%of patients experience early failure.We i...Objective:Focal therapy(FT)is a potential treatment option for limited-volume clinically-significant prostate cancer(csPCa).However,despite rigorous selection,approximately 20%of patients experience early failure.We investigated the association of transcriptomic profiles and csPCa recurrence post-FT.Methods:52 men from a phase II trial(NCT04138914)and a prospective observational cohort underwent focal cryotherapy for csPCa.Patients underwent multiparametric magnetic resonance imaging,and targeted and systematic-saturation biopsy before-and 1-year post-FT.Recurrence was defined as grade-group(GG)≥2 cancer in the 1-year post-FT biopsy.Pre-treatment lesions were profiled using the Decipher genomic classifier(GC).GC scores,luminal-basal status,tumor microenvironment and cancer hallmark pathways were correlated with csPCa recurrence.Results:Median PSA was 7.0 ng/dl;37/52(71.1%)men had GG2,12/52(23.1%)GG3,and 3/52(5.8%)GG4 cancer.Recurrence was observed in 9/52(17.3%)men.Median GC score was higher in patients with recurrence(0.60 vs 0.38,P=0.014)and remained significantly associated with recurrence after adjustment for GG(adjusted OR:1.37[95%CI:1.01-1.93],P=0.04).Luminal-proliferative tumors based on the prostate cancer-specific subtyping classifier(PSC)had more csPCa recurrence compared with luminal-differentiated(LD)and basal subtypes(30.4%vs 0%[LD]vs 15.4%[basal-neuroendocrine]and 14.3%[basal-immune],P=0.027).Higher expression of DNA repair pathway was also associated with recurrence(OR:2.12[95%CI:1.09-4.57],P=0.025).Conclusions:Higher GC score is associated with risk of csPCa recurrence post-FT.Patients with GC low-risk and PSC-LD csPCa may represent the ideal subgroup for FT.Prospective validation in a large cohort is warranted.展开更多
As one of the most seismically active regions,Sichuan Basin is a key area of seismological studies in China.This study applies a neural network model with attention mechanisms,simultaneously picking the P-wave arrival...As one of the most seismically active regions,Sichuan Basin is a key area of seismological studies in China.This study applies a neural network model with attention mechanisms,simultaneously picking the P-wave arrival times and determining the first-motion polarity.The polarity information is subsequently used to derive source focal mechanisms.The model is trained and tested using small to moderate earthquake data from June to December 2019 in Sichuan.We apply the trained model to predict first-motion polarity directions of earthquake recordings in Sichuan from January to May 2019,and then derive focal mechanism solutions using HASH algorithm with predicted results.Compared with the source mechanism solutions obtained by manual processing,the deep learning method picks more polarities from smaller events,resulting in more focal mechanism solutions.The catalog documents focal mechanism solutions of 22 events(M_(L) 2.6–4.8)from analysts during this period,whereas we obtain focal mechanism solutions of 53 events(M_(L) 1.9–4.8)through the deep learning method.The derived focal mechanism solutions for the same events are consistent with the manual solutions.This method provides an efficient way for the source mechanism inversion of small to moderate earthquakes in Sichuan region,with high stability and reliability.展开更多
We present CrazyBeachball,a MATLAB-based graphical user interface(GUI)software package designed for focal mechanism inversion using P-wave first-motion polarity and S/P amplitude ratio data.CrazyBeachball integrates s...We present CrazyBeachball,a MATLAB-based graphical user interface(GUI)software package designed for focal mechanism inversion using P-wave first-motion polarity and S/P amplitude ratio data.CrazyBeachball integrates seismic waveform visualization,first-motion polarity picking,and focal mechanism inversion into a single,interactive platform.Unlike conventional methods that involve separate,independent steps,CrazyBeachball streamlines the process and eliminates the need for external data conversion.Its user-friendly interface allows for efficient focal mechanism determination,while its human-machine interaction facilitates enhanced quality control.We demonstrate its effectiveness by determining focal mechanisms for 21 aftershocks from the 2021 M_(S)6.4 Yangbi earthquake sequence,with results aligning with the regional stress field and fault zone geometry.This open-source software package also allows for user customization,enabling adaptation for specific research needs.展开更多
On December 18,2023,an M_(s)6.2 earthquake jolted Jishishan County in the Linxia Hui Autonomous Prefecture in Northwest China's Gansu Province,causing substantial casualties and building collapses.The earthquake o...On December 18,2023,an M_(s)6.2 earthquake jolted Jishishan County in the Linxia Hui Autonomous Prefecture in Northwest China's Gansu Province,causing substantial casualties and building collapses.The earthquake occurred in the Qilian Block on the northeastern border of the Qinghai-Tibet Plateau,where faults are highly active and the geological structure is complex.In this study,we utilized methods such as relocation,focal mechanism solutions,and earthquake rupture processes to describe seismogenic faults.The results indicated that the majority of aftershocks occurred at a depth of 12 km.The centroid depth of the main shock and the depth of the maximum rupture point during the rupture process were also 12 km.Various geophysical methods exhibited a high degree of consistency in depth exploration.Aftershocks were distributed mainly to the west and north of the main shock and extended in the NNW direction,primarily through unilateral rupture.The main shock was a reverse thrust event with a small dextral strike-slip component.In this study,more regional data,such as previous GPS observations,field geological observations,and the distributions of the primary stress states in the region,were also incorporated.We inferred that the main shock was triggered by the main fault at the northern margin of the Lajishan Fault and that the movement of the main fault also activated some secondary faults.The compressive forces on both sides of the Lajishan Fault Zone led to the uplift of mountain areas,accompanied by some landslides,leading to this catastrophic earthquake event.In this article,the activity relationships among the 2022 M_(s)6.9 Menyuan earthquake,the 2019 M_(s)5.7 Xiahe earthquake,and the Jishishan earthquake under the action of regional stress are also discussed.This study provides additional evidence and new ideas for exploring the seismogenic process of the Lajishan Fault Zone and has implications for future in-depth research on underground activity in this region.展开更多
Achieving high-level integration of composite micro-nano structures with different structural characteristics through a minimalist and universal process has long been the goal pursued by advanced manufacturing researc...Achieving high-level integration of composite micro-nano structures with different structural characteristics through a minimalist and universal process has long been the goal pursued by advanced manufacturing research but is rarely explored due to the absence of instructive mechanisms.Here,we revealed a controllable ultrafast laser-induced focal volume light field and experimentally succeeded in highly efficient one-step composite structuring in multiple transparent solids.A pair of spatially coupled twin periodic structures reflecting light distribution in the focal volume are simultaneously created and independently tuned by engineering ultrafast laser-matter interaction.We demonstrated that the generated composite micro-nano structures are applicable to multi-dimensional information integration,nonlinear diffractive elements,and multi-functional optical modulation.This work presents the experimental verification of highly universal all-optical fabrication of composite micro-nano structures with independent controllability in multiple degrees of freedom,expands the current cognition of ultrafast laser-based material modification in transparent solids,and establishes a new scientific aspect of strong-field optics,namely,focal volume optics for composite structuring transparent solids.展开更多
Focal segmental glomerulosclerosis(FSGS)is a histological pattern of glomerular damage that significantly contributes to chronic kidney disease and end-stage renal disease.Its incidence is rising globally,necessitatin...Focal segmental glomerulosclerosis(FSGS)is a histological pattern of glomerular damage that significantly contributes to chronic kidney disease and end-stage renal disease.Its incidence is rising globally,necessitating timely and personalized management strategies.This paper aims to provide an updated overview of the pathophysiology,diagnosis,and therapeutic strategies for FSGS,emphasizing the importance of early interventions and tailored treatments.This editorial synthesizes key findings from recent literature to highlight advancements in understanding and managing FSGS.Emerging evidence supports the role of targeted therapies and personalized approaches in improving outcomes for FSGS patients.Advances include novel biomarkers,genetic testing,and innovative therapeutics such as transient receptor potential ion channel blockers and antisense oligonucleotides for apolipoprotein 1-related FSGS.Effective mana-gement of FSGS requires a combination of timely diagnosis,evidence-based therapeutic strategies,and ongoing research to optimize patient outcomes and address gaps in the current understanding of the disease.展开更多
BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesi...BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesion kinase(FAK)has been implicated in regulating HSC glycolysis,its precise role in activation remains unclear.AIM To investigate the effects of FAK and fructose-1,6-bisphosphatase 1(FBP1)on LF through the modulation of aerobic glycolysis in HSCs.METHODS Eighteen mice were randomly assigned to three groups:Control,carbon tetrachloride(CCl_(4))-induced LF,and CCl_(4)with FAK inhibitor treatment.Liver tissues were analyzed using transcriptomic and proteomic sequencing.Differential gene expression,Mfuzz clustering,and protein interaction network analyses identified key regulatory factors.Immunohistochemistry(IHC)and Western blot(WB)analysis were used to assess FAK and FBP1 expression,along with glycolysis-related enzymes.The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.RESULTS Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl_(4)-induced fibrosis,which was restored upon FAK inhibition.Histological staining(hematoxylin and eosin,Masson’s trichrome,Sirius red)confirmed reduced fibrosis following FAK inhibition.WB analysis demonstrated suppression of glycolysisrelated enzymes.In LX-2 cells,FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1.Exogenous recombinant FBP1 inhibited HSC activation and glycolysis.Transwell and scratch assays showed that FBP1 significantly impaired HSC migration.In addition,WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.CONCLUSION FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs,thereby improving LF.Thus,FAK and FBP1 may be potential targets for LF treatment.展开更多
Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with ani...Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,single intravenous ADR injections with dosing levels from 10 to 17 mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assessments 8 weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symptoms.Findings from the longitudinal study suggest that 6 weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.展开更多
Although the etiology of inflammatory bowel disease (IBD) remains unclear,compromised epithelial barrier integrity is believed to promote susceptibility toIBD and be associated with disease severity, suggesting that i...Although the etiology of inflammatory bowel disease (IBD) remains unclear,compromised epithelial barrier integrity is believed to promote susceptibility toIBD and be associated with disease severity, suggesting that improving gut barrierintegrity may palliate or treat IBD. Such a notion gets support from the clinicalfindings that mucosal healing in IBD patients is associated with improvedprognosis, and reduced risk of relapse or colitis-associated cancer. It thereforebecomes critical to understand the intracellular signals that regulate mucosalhealing and gut barrier integrity. Focal adhesion kinase (FAK) is a non-receptortyrosine kinase that critically modulates epithelial cell growth and mobility andhas been associated with carcinogenesis. However, studies also suggest that FAKactivation may promote mucosal healing under conditions of colitis, which shouldreduce the risk of colitis-associated cancer. These findings highlight a potentiallytransformative role for FAK in the context of IBD. Understanding the molecularmechanisms by which FAK influences gut barrier repair and mucosal integritycould offer novel therapeutic avenues for treating IBD and preventing its longtermcomplications. This review focuses on the potential role of FAK in promotingcolitis-associated mucosal healing and the underlying molecular mechanismsdriving these processes, offering critical insights into IBD pathogenesis and therapy.展开更多
High-power laser systems have opened new frontiers in scientifi research and have revolutionized various scientifi fields offering unprecedented capabilities for understanding fundamental physics and allowing unique a...High-power laser systems have opened new frontiers in scientifi research and have revolutionized various scientifi fields offering unprecedented capabilities for understanding fundamental physics and allowing unique applications.This paper details the successful commissioning of the 1 PW experimental area at the Extreme Light Infrastructure–Nuclear Physics(ELI-NP)facility in Romania,using both of the available laser arms.The experimental setup featured a short focal parabolic mirror to accelerate protons through the target normal sheath acceleration mechanism.Detailed experiments were conducted using various metallic and diamond-like carbon targets to investigate the dependence of the proton acceleration on different laser parameters.Furthermore,the paper discusses the critical role of the laser temporal profil in optimizing proton acceleration,supported by hydrodynamic simulations that are correlated with experimental outcomes.The finding underscore the potential of the ELI-NP facility to advance research in laser–plasma physics and contribute significantl to high-energy physics applications.The results of this commissioning establish a strong foundation for experiments by future users.展开更多
Chen et al demonstrated that regulator of G protein signaling(RGS)4 promotes gastric cancer(GC)progression by activating the focal adhesion kinase/phospha-tidyl-inositol-3-kinase/protein kinase B pathway and inducing ...Chen et al demonstrated that regulator of G protein signaling(RGS)4 promotes gastric cancer(GC)progression by activating the focal adhesion kinase/phospha-tidyl-inositol-3-kinase/protein kinase B pathway and inducing epithelial-mesen-chymal transition.Although their multilevel approach integrating clinical data,functional assays,and xenograft models demonstrated a key role for RGS4 in GC pathogenesis,several limitations should be considered.The mechanism of the RGS4-focal adhesion kinase interaction remains unclear,specifically whether it involves direct binding or intermediaries.The clinical analysis of 90 patients lacks stratification by GC subtypes or immune features,potentially limiting generaliz-ability.Furthermore,fully validating RGS4’s oncogenic role requires additional studies,including functional assays in chemotherapy-resistant and metastatic cell lines,metastasis models including orthotopic implantation and tail vein injection,and comparison with other RGS family members.Addressing these via targeted mechanistic studies and expanded clinical validation could strengthen RGS4’s po-tential as a therapeutic target in GC.展开更多
基金supported by the Guangdong High Level Innovation Research Institute(Grant No.2021B0909050006)the National Grand Instrument Project(Grant No.2019YFF01014402)+1 种基金the National Natural Science Foundation of China(Grant No.12205008)support from the National Science Fund for Distinguished Young Scholars(Grant No.12225501)。
文摘Experimental validation of laser intensity is particularly important for the study of fundamental physics at extremely high intensities.However,reliable diagnosis of the focal spot and peak intensity faces huge challenges.In this work,we demonstrate for the firs time that the coherent radiation farfiel patterns from laser–foil interactions can serve as an in situ,real-time,and easy-to-implement diagnostic for an ultraintense laser focus.The laser-driven electron sheets,curved by the spatially varying laser fiel and leaving the targets at nearly the speed of light,produce doughnut-shaped patterns depending on the shapes of the focal spot and the absolute laser intensities.Assisted by particle-in-cell simulations,we can achieve measurements of the intensity and the focal spot,and provide immediate feedback to optimize the focal spots for extremely high intensity.
文摘BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC)lesions,they are benign.As such,it is important to develop methods to distinguish between FNH-like lesions and HCC.AIM To evaluate diagnostically differential radiological findings between FNH-like lesions and HCC.METHODS We studied pathologically confirmed FNH-like lesions in 13 patients with alco-holic cirrhosis[10 men and 3 women;mean age:54.5±12.5(33-72)years]who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography(CT)and magnetic resonance imaging(MRI),including superparamagnetic iron oxide(SPIO)and/or gadoxetic acid-enhanced MRI.Seven patients also underwent angiography-assisted CT.RESULTS The evaluated lesion features included arterial enhancement pattern,washout appearance(low density compared with that of surrounding liver parenchyma),signal intensity on T1-weighted image(T1WI)and T2-weighted image(T2WI),central scar presence,chemical shift on in-and out-of-phase images,and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and SPIO-enhanced MRI.Eleven patients had multiple small lesions(<1.5 cm).Radiological features of FNH-like lesions included hypervascularity despite small lesions,lack of“corona-like”enhancement in the late phase on CT during hepatic angiography(CTHA),high-intensity on T1WI,slightly high-or iso-intensity on T2WI,no signal decrease in out-of-phase images,and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid.Pathologically,similar to HCC,FNH-like lesions showed many unpaired arteries and sinusoidal capillarization.CONCLUSION Overall,the present study showed that FNH-like lesions have unique radiological findings useful for differential diagnosis.Specifically,SPIO-and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.
基金Supported by the Fundamental Research Program of Shanxi Province,No.202203021222418Research Program of Shanxi Provincial Health Commission,No.2023061+2 种基金Fundamental Research Cooperation Program of Beijing-Tianjin-Hebei Region of Natural Science Foundation of Tianjin,No.22JCZXJC00140Tianjin Major Science and Technology Project,No.21ZXJBSY00110Tianjin Health and Science and Technology Project,No.TJWJ2024ZK001.
文摘BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.
基金Project supported by the National Natural Science Foundation of China(Grant No.61875148)the Key Awards Program of Cultivating Outstanding Innovative Postgraduates in Arts and Sciences of Tianjin University(Grant No.C1-2022002)+3 种基金the Talent Project of Anhui Science and Technology University(Grant No.DQYJ202304)the University-Level Research Project of Tianjin Sino-German University of Applied Sciences(Grant No.zdkt2018-007)China Association for Science and Technology Young Talent Support Project Doctoral Special Programthe National High-level University Scholarship Program for Graduate Students of China Scholarship Council(Grant No.202406250166)。
文摘We report an interesting and abnormal electromagnetic phenomenon with regard to a terajet(TJ)that is generated in a reflection mode,which is realized by placing a dielectric scatterer onto a metal reflection plate.We show that the introduction of an air hollow into metal reflection plate beneath the scatterer does not induce an expected decrease but an abnormal increase of focal length of the TJ by as much as more than three times.This abnormal phenomenon takes place in case that the air hollow is shallow and there exists a critical hollow depth for a given lateral size of air hollow.Larger than the critical depth,the phenomenon no longer occurs.It is explained from viewpoints of both ray optics in terms of role of relative portion of central waves in TJ formation and electromagnetic field theory with regard to hollow-induced phase singularities.
基金supported by National Medical Research Council Sin‐gapore,National Medical Research Council Singapore(grant numbers:TA20nov-0011,NMRC/CSA‐INV/0027/2018,CSAINV20nov‐0021)Duke‐NUS Oncology Academic Program+2 种基金Goh Foundation Proton Research ProgramNCCS Cancer FundKua Hong Pak Head and Neck Cancer Research Program.
文摘Objective:Focal therapy(FT)is a potential treatment option for limited-volume clinically-significant prostate cancer(csPCa).However,despite rigorous selection,approximately 20%of patients experience early failure.We investigated the association of transcriptomic profiles and csPCa recurrence post-FT.Methods:52 men from a phase II trial(NCT04138914)and a prospective observational cohort underwent focal cryotherapy for csPCa.Patients underwent multiparametric magnetic resonance imaging,and targeted and systematic-saturation biopsy before-and 1-year post-FT.Recurrence was defined as grade-group(GG)≥2 cancer in the 1-year post-FT biopsy.Pre-treatment lesions were profiled using the Decipher genomic classifier(GC).GC scores,luminal-basal status,tumor microenvironment and cancer hallmark pathways were correlated with csPCa recurrence.Results:Median PSA was 7.0 ng/dl;37/52(71.1%)men had GG2,12/52(23.1%)GG3,and 3/52(5.8%)GG4 cancer.Recurrence was observed in 9/52(17.3%)men.Median GC score was higher in patients with recurrence(0.60 vs 0.38,P=0.014)and remained significantly associated with recurrence after adjustment for GG(adjusted OR:1.37[95%CI:1.01-1.93],P=0.04).Luminal-proliferative tumors based on the prostate cancer-specific subtyping classifier(PSC)had more csPCa recurrence compared with luminal-differentiated(LD)and basal subtypes(30.4%vs 0%[LD]vs 15.4%[basal-neuroendocrine]and 14.3%[basal-immune],P=0.027).Higher expression of DNA repair pathway was also associated with recurrence(OR:2.12[95%CI:1.09-4.57],P=0.025).Conclusions:Higher GC score is associated with risk of csPCa recurrence post-FT.Patients with GC low-risk and PSC-LD csPCa may represent the ideal subgroup for FT.Prospective validation in a large cohort is warranted.
基金the National Key R&D Program of China(2021YFC3000701)for the financial support。
文摘As one of the most seismically active regions,Sichuan Basin is a key area of seismological studies in China.This study applies a neural network model with attention mechanisms,simultaneously picking the P-wave arrival times and determining the first-motion polarity.The polarity information is subsequently used to derive source focal mechanisms.The model is trained and tested using small to moderate earthquake data from June to December 2019 in Sichuan.We apply the trained model to predict first-motion polarity directions of earthquake recordings in Sichuan from January to May 2019,and then derive focal mechanism solutions using HASH algorithm with predicted results.Compared with the source mechanism solutions obtained by manual processing,the deep learning method picks more polarities from smaller events,resulting in more focal mechanism solutions.The catalog documents focal mechanism solutions of 22 events(M_(L) 2.6–4.8)from analysts during this period,whereas we obtain focal mechanism solutions of 53 events(M_(L) 1.9–4.8)through the deep learning method.The derived focal mechanism solutions for the same events are consistent with the manual solutions.This method provides an efficient way for the source mechanism inversion of small to moderate earthquakes in Sichuan region,with high stability and reliability.
基金supported by the National Key Research and Development Program of China(No.2022 YFC3003504)the National Natural Science Foundation of China(No.42174058)the Guangdong Provincial Key Laboratory of Geophysical High-resolution Imaging Technology(No.2022B1212010002).
文摘We present CrazyBeachball,a MATLAB-based graphical user interface(GUI)software package designed for focal mechanism inversion using P-wave first-motion polarity and S/P amplitude ratio data.CrazyBeachball integrates seismic waveform visualization,first-motion polarity picking,and focal mechanism inversion into a single,interactive platform.Unlike conventional methods that involve separate,independent steps,CrazyBeachball streamlines the process and eliminates the need for external data conversion.Its user-friendly interface allows for efficient focal mechanism determination,while its human-machine interaction facilitates enhanced quality control.We demonstrate its effectiveness by determining focal mechanisms for 21 aftershocks from the 2021 M_(S)6.4 Yangbi earthquake sequence,with results aligning with the regional stress field and fault zone geometry.This open-source software package also allows for user customization,enabling adaptation for specific research needs.
基金funded by the National Natural Science Foundation of China(Grant No.42304072)。
文摘On December 18,2023,an M_(s)6.2 earthquake jolted Jishishan County in the Linxia Hui Autonomous Prefecture in Northwest China's Gansu Province,causing substantial casualties and building collapses.The earthquake occurred in the Qilian Block on the northeastern border of the Qinghai-Tibet Plateau,where faults are highly active and the geological structure is complex.In this study,we utilized methods such as relocation,focal mechanism solutions,and earthquake rupture processes to describe seismogenic faults.The results indicated that the majority of aftershocks occurred at a depth of 12 km.The centroid depth of the main shock and the depth of the maximum rupture point during the rupture process were also 12 km.Various geophysical methods exhibited a high degree of consistency in depth exploration.Aftershocks were distributed mainly to the west and north of the main shock and extended in the NNW direction,primarily through unilateral rupture.The main shock was a reverse thrust event with a small dextral strike-slip component.In this study,more regional data,such as previous GPS observations,field geological observations,and the distributions of the primary stress states in the region,were also incorporated.We inferred that the main shock was triggered by the main fault at the northern margin of the Lajishan Fault and that the movement of the main fault also activated some secondary faults.The compressive forces on both sides of the Lajishan Fault Zone led to the uplift of mountain areas,accompanied by some landslides,leading to this catastrophic earthquake event.In this article,the activity relationships among the 2022 M_(s)6.9 Menyuan earthquake,the 2019 M_(s)5.7 Xiahe earthquake,and the Jishishan earthquake under the action of regional stress are also discussed.This study provides additional evidence and new ideas for exploring the seismogenic process of the Lajishan Fault Zone and has implications for future in-depth research on underground activity in this region.
基金financially supported by the National Key Research and Development Program of China(No.2021YFB2802001)the National Natural Science Foundation of China(Grant Nos.12304349,U20A20211,62275233)the Postdoctoral Fellowship Program of CPSF(GZB20230628,GZC20241465)。
文摘Achieving high-level integration of composite micro-nano structures with different structural characteristics through a minimalist and universal process has long been the goal pursued by advanced manufacturing research but is rarely explored due to the absence of instructive mechanisms.Here,we revealed a controllable ultrafast laser-induced focal volume light field and experimentally succeeded in highly efficient one-step composite structuring in multiple transparent solids.A pair of spatially coupled twin periodic structures reflecting light distribution in the focal volume are simultaneously created and independently tuned by engineering ultrafast laser-matter interaction.We demonstrated that the generated composite micro-nano structures are applicable to multi-dimensional information integration,nonlinear diffractive elements,and multi-functional optical modulation.This work presents the experimental verification of highly universal all-optical fabrication of composite micro-nano structures with independent controllability in multiple degrees of freedom,expands the current cognition of ultrafast laser-based material modification in transparent solids,and establishes a new scientific aspect of strong-field optics,namely,focal volume optics for composite structuring transparent solids.
文摘Focal segmental glomerulosclerosis(FSGS)is a histological pattern of glomerular damage that significantly contributes to chronic kidney disease and end-stage renal disease.Its incidence is rising globally,necessitating timely and personalized management strategies.This paper aims to provide an updated overview of the pathophysiology,diagnosis,and therapeutic strategies for FSGS,emphasizing the importance of early interventions and tailored treatments.This editorial synthesizes key findings from recent literature to highlight advancements in understanding and managing FSGS.Emerging evidence supports the role of targeted therapies and personalized approaches in improving outcomes for FSGS patients.Advances include novel biomarkers,genetic testing,and innovative therapeutics such as transient receptor potential ion channel blockers and antisense oligonucleotides for apolipoprotein 1-related FSGS.Effective mana-gement of FSGS requires a combination of timely diagnosis,evidence-based therapeutic strategies,and ongoing research to optimize patient outcomes and address gaps in the current understanding of the disease.
基金Supported by the Science and Technology Program of the Guizhou Province,No.[2021]094National Natural Science Foundation of China,No.82060116 and No.82260129+1 种基金Guizhou Provincial Science and Technology Program,No.QKHJC-ZK[2023]214Doctoral Research Start-up Fund Project of Guizhou Medical University,No.gyfybsky[2021]63.
文摘BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesion kinase(FAK)has been implicated in regulating HSC glycolysis,its precise role in activation remains unclear.AIM To investigate the effects of FAK and fructose-1,6-bisphosphatase 1(FBP1)on LF through the modulation of aerobic glycolysis in HSCs.METHODS Eighteen mice were randomly assigned to three groups:Control,carbon tetrachloride(CCl_(4))-induced LF,and CCl_(4)with FAK inhibitor treatment.Liver tissues were analyzed using transcriptomic and proteomic sequencing.Differential gene expression,Mfuzz clustering,and protein interaction network analyses identified key regulatory factors.Immunohistochemistry(IHC)and Western blot(WB)analysis were used to assess FAK and FBP1 expression,along with glycolysis-related enzymes.The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.RESULTS Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl_(4)-induced fibrosis,which was restored upon FAK inhibition.Histological staining(hematoxylin and eosin,Masson’s trichrome,Sirius red)confirmed reduced fibrosis following FAK inhibition.WB analysis demonstrated suppression of glycolysisrelated enzymes.In LX-2 cells,FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1.Exogenous recombinant FBP1 inhibited HSC activation and glycolysis.Transwell and scratch assays showed that FBP1 significantly impaired HSC migration.In addition,WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.CONCLUSION FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs,thereby improving LF.Thus,FAK and FBP1 may be potential targets for LF treatment.
基金United States Department of Defense Office of the Congressionally Directed Medical Research Programs(CDMRP),Grant/Award Number:W81XWH-22-1-0176。
文摘Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,single intravenous ADR injections with dosing levels from 10 to 17 mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assessments 8 weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symptoms.Findings from the longitudinal study suggest that 6 weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.
文摘Although the etiology of inflammatory bowel disease (IBD) remains unclear,compromised epithelial barrier integrity is believed to promote susceptibility toIBD and be associated with disease severity, suggesting that improving gut barrierintegrity may palliate or treat IBD. Such a notion gets support from the clinicalfindings that mucosal healing in IBD patients is associated with improvedprognosis, and reduced risk of relapse or colitis-associated cancer. It thereforebecomes critical to understand the intracellular signals that regulate mucosalhealing and gut barrier integrity. Focal adhesion kinase (FAK) is a non-receptortyrosine kinase that critically modulates epithelial cell growth and mobility andhas been associated with carcinogenesis. However, studies also suggest that FAKactivation may promote mucosal healing under conditions of colitis, which shouldreduce the risk of colitis-associated cancer. These findings highlight a potentiallytransformative role for FAK in the context of IBD. Understanding the molecularmechanisms by which FAK influences gut barrier repair and mucosal integritycould offer novel therapeutic avenues for treating IBD and preventing its longtermcomplications. This review focuses on the potential role of FAK in promotingcolitis-associated mucosal healing and the underlying molecular mechanismsdriving these processes, offering critical insights into IBD pathogenesis and therapy.
基金supported by the Extreme Light Infrastructure–Nuclear Physics(ELI-NP)PhaseⅡa project co-finance by the Romanian Government and the European Union through the European Regional Development Fund,by the Romanian Ministry of Education and Research CNCS-UEFISCDI(Project No.PN-ⅡIP4-IDPCCF-2016-0164)+1 种基金Nucleu Projects(Grant No.PN 23210105 and 19060105)supports ELI-NP through IOSIN funds as a Facility of National Interest。
文摘High-power laser systems have opened new frontiers in scientifi research and have revolutionized various scientifi fields offering unprecedented capabilities for understanding fundamental physics and allowing unique applications.This paper details the successful commissioning of the 1 PW experimental area at the Extreme Light Infrastructure–Nuclear Physics(ELI-NP)facility in Romania,using both of the available laser arms.The experimental setup featured a short focal parabolic mirror to accelerate protons through the target normal sheath acceleration mechanism.Detailed experiments were conducted using various metallic and diamond-like carbon targets to investigate the dependence of the proton acceleration on different laser parameters.Furthermore,the paper discusses the critical role of the laser temporal profil in optimizing proton acceleration,supported by hydrodynamic simulations that are correlated with experimental outcomes.The finding underscore the potential of the ELI-NP facility to advance research in laser–plasma physics and contribute significantl to high-energy physics applications.The results of this commissioning establish a strong foundation for experiments by future users.
文摘Chen et al demonstrated that regulator of G protein signaling(RGS)4 promotes gastric cancer(GC)progression by activating the focal adhesion kinase/phospha-tidyl-inositol-3-kinase/protein kinase B pathway and inducing epithelial-mesen-chymal transition.Although their multilevel approach integrating clinical data,functional assays,and xenograft models demonstrated a key role for RGS4 in GC pathogenesis,several limitations should be considered.The mechanism of the RGS4-focal adhesion kinase interaction remains unclear,specifically whether it involves direct binding or intermediaries.The clinical analysis of 90 patients lacks stratification by GC subtypes or immune features,potentially limiting generaliz-ability.Furthermore,fully validating RGS4’s oncogenic role requires additional studies,including functional assays in chemotherapy-resistant and metastatic cell lines,metastasis models including orthotopic implantation and tail vein injection,and comparison with other RGS family members.Addressing these via targeted mechanistic studies and expanded clinical validation could strengthen RGS4’s po-tential as a therapeutic target in GC.
