BACKGROUND Percutaneous liver biopsies,including coaxial needle biopsy(CNB),are the pre-ferred method for tissue sampling to diagnose or characterize an array of hepatic conditions.Despite the advent of intraprocedura...BACKGROUND Percutaneous liver biopsies,including coaxial needle biopsy(CNB),are the pre-ferred method for tissue sampling to diagnose or characterize an array of hepatic conditions.Despite the advent of intraprocedural image guidance,and various“plugging”techniques,bleeding remains a frequent and potentially highly mor-bid complication,particularly in patients with bleeding risks.Thus,post-biopsy bleeding risk leads to extended patient monitoring,and in significant cases,ad-ditional imaging,intervention,and even surgery.Very rarely,death has resulted.CASE SUMMARY We report a series of five image-guided liver biopsy cases undertaken due to a variety of clinical conditions followed by the use of a new electrocautery hemo-stasis device called SinglePass Kronos.Indications for the CNB included non-alcoholic steatohepatitis,hepatocellular carcinoma and cirrhosis,abnormal liver function tests with positive autoimmune serologies,abnormal imaging findings,and jaundice.All biopsy procedures were successful with no complications th-rough 30 days following CNB.Post-procedure ultrasound confirmed the absence of bleeding in all five cases.CONCLUSION Hemostasis of CNB tracts using SinglePass Kronos was obtained in all cases.Ad-ditional study of this device is warranted.展开更多
How the strong segmentation of cascade reservoir dams and the spatiotemporal changes of sediment retention volume affect the river morphology adjustment in the reservoir area is a scientific issue worthy of exploratio...How the strong segmentation of cascade reservoir dams and the spatiotemporal changes of sediment retention volume affect the river morphology adjustment in the reservoir area is a scientific issue worthy of exploration.This study aims to reveal the adjustment mechanism of the thalweg longitudinal profile of cascade reservoirs.This study focuses on the Xiangjiaba and Xiluodu reservoirs located in the lower reaches of the Jinsha River.Utilizing multi-period observational data of thalweg elevation in reservoir reaches both before and after dam construction,the research employs statistical,geomorphological,and sedimentological methodologies to analyze variation characteristics in the measured curves,trend curves,and theoretical fitting curves of the thalweg longitudinal profile.The investigation ultimately reveals two distinct adjustment patterns in the longitudinal profiles of these cascade reservoirs:the concave curve type and the convex curve type.The former is characterized by weak riverbed scouring and silting changed to rapid aggradation in the upstream section of the reservoir area after dam closure,then changed to slow aggradation in the whole reservoir area,which is the common feature of reservoirs that were built earlier and are relatively located in the downstream(such as the Xiangjiaba Reservoir).The latter is characterized by a straight line or concave curve type with weak riverbed scouring and silting before the dam closure changed to a convex curve type with strong siltation after dam closure,which is the characteristic of reservoirs that were built later and are relatively located in the upstream(such as the Xiluodu Reservoir).The adjustment of the cascade reservoir longitudinal profile is controlled by the spatiotemporal changes of the sediment deposition volume and sedimentation rate in the reservoir area,and the alternating changes of the hydrodynamic gradient and regulation mode affect the spatial heterogeneity of the sedimentation rate.The research results are helpful for understanding the adjustment mechanism of the cascade reservoir longitudinal profile in similar areas and have a guiding role in predicting the adjustment trend of the cascade reservoir longitudinal profile without observation data.展开更多
Marine heatwave(MHW)events refer to periods of significantly elevated sea surface temperatures(SST),persisting from days to months,with significant impacts on marine ecosystems,including increased mortality among mari...Marine heatwave(MHW)events refer to periods of significantly elevated sea surface temperatures(SST),persisting from days to months,with significant impacts on marine ecosystems,including increased mortality among marine life and coral bleaching.Forecasting MHW events are crucial to mitigate their harmful effects.This study presents a twostep forecasting process:short-term SST prediction followed by MHW event detection based on the forecasted SST.Firstly,we developed the“SST-MHW-DL”model using the ConvLSTM architecture,which incorporates an attention mechanism to enhance both SST forecasting and MHW event detection.The model utilizes SST data from the preceding 60 d to forecast SST and detect MHW events for the subsequent 15 d.Verification results for SST forecasting demonstrate a root mean square error(RMSE)of 0.64℃,a mean absolute percentage error(MAPE)of 2.05%,and a coefficient of determination(R^(2))of 0.85,indicating the model’s ability to accurately predict future temperatures by leveraging historical sea temperature information.For MHW event detection using forecasted SST,the evaluation metrics of“accuracy”,“precision”,and“recall”achieved values of 0.77,0.73,and 0.43,respectively,demonstrating the model’s capability to capture the occurrence of MHW events accurately.Furthermore,the attention-enhanced mechanism reveals that recent SST variations within the past 10 days have the most significant impact on forecasting accuracy,while variations in deep-sea regions and along the Taiwan Strait significantly contribute to the model’s efficacy in capturing spatial characteristics.Additionally,the proposed model and temporal mechanism were applied to detect MHWs in the Atlantic Ocean.By inputting 30 d of SST data,the model predicted SST with an RMSE of 1.02℃and an R^(2)of 0.94.The accuracy,precision,and recall for MHW detection were 0.79,0.78,and 0.62,respectively,further demonstrating the model’s robustness and usability.展开更多
BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number o...BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number of reports showing that,in selected scenarios,conservative management through graft repair represents a feasible option,challenging traditional approaches.CASE SUMMARY We describe the case of a 37-year-old sensitized XY patient who experienced early spontaneous graft rupture after receiving his second deceased donor kidney transplant.Following temporary hemodynamic stabilization and abdominal contrast enhanced computed tomography scan assessment,the recipient was brought back to theatre for surgical exploration.Possible causes of irreversible graft damage were immediately ruled out.The fractured upper pole of the transplanted kidney was repaired using a fibrin sealant,external compression,and a tailored polyglactin 910 mesh wrapped around the graft.The post-operative course was uneventful.After 20 months of follow up,the patient is doing very well,with excellent renal function and complete reabsorption of the mesh,as demonstrated by serial ultrasound evaluations of the graft.CONCLUSION Amid organ shortages and sensitized patients,graft nephrectomy is reserved for severe injuries;repair using sealants and mesh is effective.展开更多
We demonstrate for the first time the critical influence of binder molecular weight on the performance of slurry-cast lithium nickel manganese cobalt oxide(NMC)cathodes in sulfide-based all-solid-state batteries(SSBs)...We demonstrate for the first time the critical influence of binder molecular weight on the performance of slurry-cast lithium nickel manganese cobalt oxide(NMC)cathodes in sulfide-based all-solid-state batteries(SSBs).SSBs are increasingly recognized as a safer and potentially more efficient alternative to traditional Li-ion batteries,owing to the superior ionic conductivities and inherent safety features of sulfide solid electrolytes.However,the integration of high-voltage NMC cathodes with sheet-type sulfide solid electrolytes presents significant fabrication challenges.Our findings reveal that higher molecular weight binders not only enhance the discharge capacity and cycle life of these cathodes but also ensure robust adhesion and structural integrity.By optimizing binder molecular weights,we effectively shield the active materials from degradation and mechanical stress,significantly boosting the functionality and longevity of SSBs.These results underscore the paramount importance of binder properties in advancing the practical application of high-performance all-solid-state batteries.展开更多
CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identif...CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.展开更多
For nickel-based superalloys with medium volume-fractionγʹphase(20%-40%),dual or multi-stage aging treatments are usually conducted to generate a microstructure containing the multimodal distri-bution ofγʹfor a bala...For nickel-based superalloys with medium volume-fractionγʹphase(20%-40%),dual or multi-stage aging treatments are usually conducted to generate a microstructure containing the multimodal distri-bution ofγʹfor a balance of strength and plasticity.In the present study,the microstructure and high-temperature properties of a novel cast nickel-based superalloy K4800 were investigated after being sub-jected to three heat treatments(HT)procedures,namely HT1:1180℃/4 h+1090℃/2 h+800℃/16 h,HT2:1180℃/4 h+1060℃/2 h+800℃/16 h and HT3:1180℃/4 h+800℃/16 h.It was found that the sub-solvus aging treatments at 1090 and 1060℃ precipitated sub-micron-sized(∼300 nm)primaryγʹphase which enhanced the ductility during 800℃ tensile(the total elongation of T1,T2,and T3 sam-ples were 6.75%,7.3%,and 3.25%,respectively)without evidently impairing the strength.After careful microstructure observation and deformation mechanism analysis,the enhancement of elongation was ra-tionalized that the precipitation of the sub-micron-sized primaryγʹphase decreased the volume-fraction and size of the nanometer-sizedγʹphase which was precipitated at 800℃,and simultaneously,pro-moted the dislocation movement by suppressing the non-planar slip.However,an excessive amount of the sub-micron-sized primaryγʹphase led to a faster ripening process of the nanometer-sizedγʹduring creep,which decreased the creep life at 800℃/430 MPa(T1:125 h,T2:199 h,and T3:198 h).Based on this,we monitored the number density of nanometer-sizedγʹphase coexisting with different amounts of largeγʹduring creep.An area fraction less than 7%of the sub-micron-sizedγʹphase was considered to have little detrimental effect on the creep life of K4800 alloy,which corresponded to a sub-solvus temperature range about 1080-1090℃.展开更多
Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GN...Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].展开更多
Background: Cryptococcus neoformans is an opportunistic fungal pathogen that primarily affects immunocompromised individuals. While traditional histologic methods such as hematoxylin and eosin (H&E) staining can s...Background: Cryptococcus neoformans is an opportunistic fungal pathogen that primarily affects immunocompromised individuals. While traditional histologic methods such as hematoxylin and eosin (H&E) staining can sometimes identify fungal organisms, definitive diagnosis typically requires microbiological culture or molecular testing. Stimulated Raman Histology (SRH) is an emerging imaging technology that enables rapid, label-free tissue analysis, potentially improving intraoperative diagnostic workflows. Aim: This case report explores the utility of SRH for the real-time identification of pulmonary cryptococcosis, highlighting its potential to enhance tissue triage and expedite diagnosis. Case Presentation: We report a 44-year-old man with a history of smoking and alcohol use who presented with a right lower lung mass. An ION robotic-assisted bronchoscopy was performed, and SRH was used intraoperatively for real-time tissue evaluation. Within approximately 90 seconds, SRH provided morphologic findings indicative of Cryptococcus neoformans, prompting additional microbiological testing, which confirmed the diagnosis. The patient required a six-week hospitalization with antifungal therapy. Conclusion: This case demonstrates the potential of SRH as a rapid, intraoperative diagnostic tool for detecting fungal infections in pulmonary specimens. By enabling real-time morphological assessment, SRH can optimize biopsy specimen triage, reduce the need for repeat procedures, and improve patient management. Integrating SRH into diagnostic workflows may be particularly beneficial in resource-limited settings, where timely cryptococcosis diagnosis is critical.展开更多
Soft tissue tumors in the hand have a broad differential diagnosis. Included in the list of differential diagnoses for these tumors are Schwannomas, which are benign tumors within the peripheral nervous system [1]. Sc...Soft tissue tumors in the hand have a broad differential diagnosis. Included in the list of differential diagnoses for these tumors are Schwannomas, which are benign tumors within the peripheral nervous system [1]. Schwannomas are uncommon within the upper extremity, and they are exceedingly rare within the hand and wrist [1]. We describe a case of an 80-year-old female presented with a soft tissue mass within her right thumb. She underwent excisional biopsy of the mass, and pathology showed features consistent with schwannoma. She had resolution of her symptoms thereafter. We discuss the differential diagnosis for soft-tissue tumors in this location. When assessing patients with soft tissue tumors of the hand and wrist, it is important for the treating provider to maintain a broad differential diagnosis in order to facilitate appropriate management of these lesions.展开更多
In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care ...In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care floor and diagnosed with juvenile dermatomyositis and found to be positive for anti-Mi-2 alpha, anti-Mi-2 beta, and anti-MDA-5 antibodies. He gradually improved with a combination of steroid, immunomodulatory treatment, and physical therapy. This case outlines the clinical course of a patient with this rare disorder as well as the importance of understanding the role of associated antibodies to manage potential long-term sequelae.展开更多
Situated in the semi-arid regions of North China,the Nihewan Basin documents the fluvio-lacustrine sequence and Pleistocene archaeological sites,offering an excellent opportunity to investigate human adaptation to env...Situated in the semi-arid regions of North China,the Nihewan Basin documents the fluvio-lacustrine sequence and Pleistocene archaeological sites,offering an excellent opportunity to investigate human adaptation to environmental change in East Asia,especially in North China.However,paleoenvironmental datasets from Middle Pleistocene archaeological sites are not fully understood.Focusing on the evidence from the 0.63-0.49 Ma-old site of Jijiazhuang(Nihewan Basin,North China),this paper presents the results of various environmental indicators from the site context.Moreover,it explores the links between hominin behavioral adaptations and ecological variability during the extra-long interglacial period in North China.Sedimentological features of the excavated section indicate that the site was formed in the margin of the Nihewan paleolake.Based on well-constructed pollen,sediment grain size,color reflectance,and major geochemical element analyses,five stages of environmental changes were identified during site formation.This study indicates that hominins occupied the site at the early part of Stage 2,when the Nihewan paleolake had a relatively low water level and the climate was temperate,with strong weathering intensity dominated by wooded grassland landscapes.In conclusion,the results suggest that the extra-long duration of interglacial or mild stadial climate events(MISs 15-13)in the Northern Hemisphere may have provided favorable conditions for increased technological innovations and adaptive strategies among Middle Pleistocene hominins in the Nihewan Basin even in North China.展开更多
The prediction of new fluorooxoborates as ultraviolet(UV)/deep ultraviolet(DUV)opto-electronic functional materials from a largely unexplored chemical space is a challenging task.It has been suggested that the anionic...The prediction of new fluorooxoborates as ultraviolet(UV)/deep ultraviolet(DUV)opto-electronic functional materials from a largely unexplored chemical space is a challenging task.It has been suggested that the anionic frameworks formed by B–O and B–O–F units significantly determine the physical properties of fluorooxoborates.Therefore,the rational design of anionic frameworks could facilitate the materials discovery process.Herein,we propose that a candidate anionic framework can be efficiently derived from an existing one by slightly altering its oxygen content.Following this idea,we hypothesized the existence of a 1D[B_(3)O_(5)F]_(∞)chain from the wellknown 2D[B_(6)O_(9)F_(2_)]_(∞)layer.Accordingly,seven CaB_(3)O_(5)F structures with the expected anionic framework were successfully predicted.First-principles calculations show that all these structures have potential in the UV/DUV birefringent or nonlinear optical(NLO)material field,indicating that the 1D[B_(3)O_(5)F]_(∞)chain is indeed a promising anionic framework for achieving UV/DUV birefringent and NLO performance.展开更多
The effects of the built environment factors on urban vitality have attracted wide attention in the urban planning fields in recent years,but few studies have considered the variables’relative importance and their no...The effects of the built environment factors on urban vitality have attracted wide attention in the urban planning fields in recent years,but few studies have considered the variables’relative importance and their nonlinear effects on urban vitality.Taking a Chinese metropolis—Hangzhou as a case study,this study applied the gradient boosting decision tree(GBDT)model to explore the nonlinear effects of the 5D factors of the urban built environment on urban social vitality and economic vitality and the importance of variables.The results show that the GBDT model has better goodness of fit than the traditional ordinary least squares(OLS)regression in the urban vitality models.The urban built environment plays an important role in affecting urban vitality,while built environment designs witness the most important effect.Specifically,the density of shopping facilities,medical facilities,and road networks are the most important factors affecting urban social vitality,while road network density,destination accessibility,and population density play the most important roles in affecting urban economic vitality.Finally,the urban built environment factors have nonlinear threshold effects on both urban economic and social vitality in Hangzhou,with differing nonlinear response patterns observed between social and economic dimensions.展开更多
Accurate estimation of Zenith Tropospheric Delay(ZTD)is essential for mitigating atmospheric effects in radio astronomical observations and improving the retrieval of precipitable water vapor(PWV).In this study,we fir...Accurate estimation of Zenith Tropospheric Delay(ZTD)is essential for mitigating atmospheric effects in radio astronomical observations and improving the retrieval of precipitable water vapor(PWV).In this study,we first analyze the periodic characteristics of ZTD at the NanShan Radio Telescope site using Fourier transform,revealing its dominant seasonal variations,and then investigate the correlation between ZTD and local meteorological parameters,to better understand atmospheric influences on tropospheric delay.Based on these analyses,we propose a hybrid deep learning Gated Recurrent Units-Long Short-Term Memory model,incorporating meteorological parameters as external inputs to enhance ZTD forecasting accuracy.Experimental results demonstrate that the proposed approach achieves a Root Mean Squared Error of 7.97 mm and a correlation coefficient R of 96%,significantly outperforming traditional empirical models and standalone deep learning architectures.These findings indicate that the model effectively captures both short-term dynamics and long-term dependencies in ZTD variations.The improved ZTD predictions not only contribute to reducing atmospheric errors in radio astronomical observations but also provide a more reliable basis for PWV retrieval and forecasting.This study highlights the potential of deep learning in tropospheric delay modeling,offering advancements in both atmospheric science and geodetic applications.展开更多
In the last two decades,seismic resilience(SR)has been developed as a main concept for the assessment of the structural vulnerabilities of buildings and city centres.In particular,historical centers consist of adjacen...In the last two decades,seismic resilience(SR)has been developed as a main concept for the assessment of the structural vulnerabilities of buildings and city centres.In particular,historical centers consist of adjacent buildings organized in blocks with common characteristics and similar typologies.The paper proposes a meth-odology to quantify SR for urban regions,by overcoming the state of the art studies that focus on assessing the SR for singular buildings.In this regard,the presented methodology may calculate the SR of blocks of buildings for the assessment of recovery investments of historical city centers.The main idea is to assess the level of vulnerability by accurate 3D surveys and visual inspections in order to select empirical fragility curves.The proposed methodology was herein applied to the city center of San Marino,designated by UNESCO as a world heritage site.展开更多
Scale effects and evaluation models are crucial to the accuracy of landscape ecological risk evaluation.However,most studies conduct these evaluations at a single scale or with a single model,ignoring potential scale ...Scale effects and evaluation models are crucial to the accuracy of landscape ecological risk evaluation.However,most studies conduct these evaluations at a single scale or with a single model,ignoring potential scale effects and changes in landscape patterns.To address this,we took the Leshan City in Sichuan Province of China as a study case.We determined that the optimal spatial granularity for the study area is 150 m by analyzing the sensitivities of eight landscape pattern indices such as landscape fragmentation,landscape spreading,and Shannon's diversity at different spatial granularities,and employing the inflection point identification method.Building on this,we constructed a landscape pattern index model(ERI model)and a landscape pattern index model coupled with the ecological process of soil erosion(SI-ERI model)by incorporating the natural geographic factors of the study area.We used the ERI and SI-ERI models to evaluate the landscape ecological risk of Leshan City across multiple scales,including ecological,administrative,and sample scales.After conducting overlay and spatial autocorrelation analyses of the multi-scale evaluation results,we determined that the administrative scale is optimal for evaluating landscape ecological risk in the study area.At this scale,we verified the accuracy and reliability of the two models'evaluation results against the actual ecological environment in typical areas within the study area.The findings indicated that the SI-ERI model provided more precise and accurate spatial characterization,effectively reflecting the actual landscape ecological risk of Leshan City.According to the SI-ERI model's evaluation results at the administrative scale,Leshan City's overall risk level is relatively low,with good ecological environmental quality.Low-risk areas constitute 56.16%and medium-low-risk areas make up 23.81%,aligning closely with the city's actual situation.This study thus offers a scientific basis and theoretical reference for managing ecological risks and planning urban development in Leshan City.展开更多
Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer （mCRPC）. The past year and a half has been marked by un...Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer （mCRPC）. The past year and a half has been marked by unprecedented progress in treatments for this disease. Three positive phase III clinical trials have emerged, each evaluating agents （sipuleuceI-T, cabazitaxel and abiraterone） with distinct mechanisms of action. Herein, the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC. The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past. We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome. The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.展开更多
The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the c...The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the clinical treatment of bacterial meningitis challenging.Herein,a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis,to overcome the low drug concentration and drug resistance.This strategy was achieved by a proteinsupported Au nanozyme(ANZ).With a particle size of less than 10 nm,it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H_(2)O_(2).Benefiting from the cascade catalytic amplification effect generated by its dual enzymelike activities,ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro.Notably,small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration.In a mouse model of bacterial meningitis,the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone.Additionally,the meningitis mice exhibited undamaged cognitive and behavioral abilities,indicating the excellent biocompatibility of ANZ.The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation,strong antibacterial efficacy and does not lead to bacterial resistance.It holds broad prospects for the treatment of bacterial meningitis.展开更多
CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been d...CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been developed into a series of powerful gene‐editing tools. As the natural inhibitors of CRISPR‐Cas systems, anti‐CRISPRs (Acrs) can be used as the “off‐switch” for CRISPR‐Cas systems to limit the off‐target effects caused by Cas9. Since the discovery of CRISPR‐Cas systems, much research has focused on the identification, mechanisms and applications of Acrs. In light of the rapid development and scientific significance of this field, this review summarizes the history and research status of Acrs, and considers future applications.展开更多
文摘BACKGROUND Percutaneous liver biopsies,including coaxial needle biopsy(CNB),are the pre-ferred method for tissue sampling to diagnose or characterize an array of hepatic conditions.Despite the advent of intraprocedural image guidance,and various“plugging”techniques,bleeding remains a frequent and potentially highly mor-bid complication,particularly in patients with bleeding risks.Thus,post-biopsy bleeding risk leads to extended patient monitoring,and in significant cases,ad-ditional imaging,intervention,and even surgery.Very rarely,death has resulted.CASE SUMMARY We report a series of five image-guided liver biopsy cases undertaken due to a variety of clinical conditions followed by the use of a new electrocautery hemo-stasis device called SinglePass Kronos.Indications for the CNB included non-alcoholic steatohepatitis,hepatocellular carcinoma and cirrhosis,abnormal liver function tests with positive autoimmune serologies,abnormal imaging findings,and jaundice.All biopsy procedures were successful with no complications th-rough 30 days following CNB.Post-procedure ultrasound confirmed the absence of bleeding in all five cases.CONCLUSION Hemostasis of CNB tracts using SinglePass Kronos was obtained in all cases.Ad-ditional study of this device is warranted.
基金National Key R&D Program of China,No.2022YFC3203903National Natural Science Foundation of China,No.42371010,No.41971004。
文摘How the strong segmentation of cascade reservoir dams and the spatiotemporal changes of sediment retention volume affect the river morphology adjustment in the reservoir area is a scientific issue worthy of exploration.This study aims to reveal the adjustment mechanism of the thalweg longitudinal profile of cascade reservoirs.This study focuses on the Xiangjiaba and Xiluodu reservoirs located in the lower reaches of the Jinsha River.Utilizing multi-period observational data of thalweg elevation in reservoir reaches both before and after dam construction,the research employs statistical,geomorphological,and sedimentological methodologies to analyze variation characteristics in the measured curves,trend curves,and theoretical fitting curves of the thalweg longitudinal profile.The investigation ultimately reveals two distinct adjustment patterns in the longitudinal profiles of these cascade reservoirs:the concave curve type and the convex curve type.The former is characterized by weak riverbed scouring and silting changed to rapid aggradation in the upstream section of the reservoir area after dam closure,then changed to slow aggradation in the whole reservoir area,which is the common feature of reservoirs that were built earlier and are relatively located in the downstream(such as the Xiangjiaba Reservoir).The latter is characterized by a straight line or concave curve type with weak riverbed scouring and silting before the dam closure changed to a convex curve type with strong siltation after dam closure,which is the characteristic of reservoirs that were built later and are relatively located in the upstream(such as the Xiluodu Reservoir).The adjustment of the cascade reservoir longitudinal profile is controlled by the spatiotemporal changes of the sediment deposition volume and sedimentation rate in the reservoir area,and the alternating changes of the hydrodynamic gradient and regulation mode affect the spatial heterogeneity of the sedimentation rate.The research results are helpful for understanding the adjustment mechanism of the cascade reservoir longitudinal profile in similar areas and have a guiding role in predicting the adjustment trend of the cascade reservoir longitudinal profile without observation data.
基金The National Natural Science Foundation of China under contract Nos 42376175,42090044 and U2006211。
文摘Marine heatwave(MHW)events refer to periods of significantly elevated sea surface temperatures(SST),persisting from days to months,with significant impacts on marine ecosystems,including increased mortality among marine life and coral bleaching.Forecasting MHW events are crucial to mitigate their harmful effects.This study presents a twostep forecasting process:short-term SST prediction followed by MHW event detection based on the forecasted SST.Firstly,we developed the“SST-MHW-DL”model using the ConvLSTM architecture,which incorporates an attention mechanism to enhance both SST forecasting and MHW event detection.The model utilizes SST data from the preceding 60 d to forecast SST and detect MHW events for the subsequent 15 d.Verification results for SST forecasting demonstrate a root mean square error(RMSE)of 0.64℃,a mean absolute percentage error(MAPE)of 2.05%,and a coefficient of determination(R^(2))of 0.85,indicating the model’s ability to accurately predict future temperatures by leveraging historical sea temperature information.For MHW event detection using forecasted SST,the evaluation metrics of“accuracy”,“precision”,and“recall”achieved values of 0.77,0.73,and 0.43,respectively,demonstrating the model’s capability to capture the occurrence of MHW events accurately.Furthermore,the attention-enhanced mechanism reveals that recent SST variations within the past 10 days have the most significant impact on forecasting accuracy,while variations in deep-sea regions and along the Taiwan Strait significantly contribute to the model’s efficacy in capturing spatial characteristics.Additionally,the proposed model and temporal mechanism were applied to detect MHWs in the Atlantic Ocean.By inputting 30 d of SST data,the model predicted SST with an RMSE of 1.02℃and an R^(2)of 0.94.The accuracy,precision,and recall for MHW detection were 0.79,0.78,and 0.62,respectively,further demonstrating the model’s robustness and usability.
文摘BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number of reports showing that,in selected scenarios,conservative management through graft repair represents a feasible option,challenging traditional approaches.CASE SUMMARY We describe the case of a 37-year-old sensitized XY patient who experienced early spontaneous graft rupture after receiving his second deceased donor kidney transplant.Following temporary hemodynamic stabilization and abdominal contrast enhanced computed tomography scan assessment,the recipient was brought back to theatre for surgical exploration.Possible causes of irreversible graft damage were immediately ruled out.The fractured upper pole of the transplanted kidney was repaired using a fibrin sealant,external compression,and a tailored polyglactin 910 mesh wrapped around the graft.The post-operative course was uneventful.After 20 months of follow up,the patient is doing very well,with excellent renal function and complete reabsorption of the mesh,as demonstrated by serial ultrasound evaluations of the graft.CONCLUSION Amid organ shortages and sensitized patients,graft nephrectomy is reserved for severe injuries;repair using sealants and mesh is effective.
基金partially sponsored by the Office of Energy Efficiency and Renewable Energy(EERE)in the Vehicle Technologies Office(VTO)through the Advanced Battery Materials Research(BMR)Program,managed by DrsThe Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan(http://energy.gov/downloads/doe-public-access-plan).
文摘We demonstrate for the first time the critical influence of binder molecular weight on the performance of slurry-cast lithium nickel manganese cobalt oxide(NMC)cathodes in sulfide-based all-solid-state batteries(SSBs).SSBs are increasingly recognized as a safer and potentially more efficient alternative to traditional Li-ion batteries,owing to the superior ionic conductivities and inherent safety features of sulfide solid electrolytes.However,the integration of high-voltage NMC cathodes with sheet-type sulfide solid electrolytes presents significant fabrication challenges.Our findings reveal that higher molecular weight binders not only enhance the discharge capacity and cycle life of these cathodes but also ensure robust adhesion and structural integrity.By optimizing binder molecular weights,we effectively shield the active materials from degradation and mechanical stress,significantly boosting the functionality and longevity of SSBs.These results underscore the paramount importance of binder properties in advancing the practical application of high-performance all-solid-state batteries.
基金supported by grants from the Foundation for Distinguished Young Talents in Higher Education of Guangdong,China(2024KQNCX157)Our work was also supported in part by the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science,BNU-HKBU United International College(2022B1212010006)+1 种基金in part by the Guangdong Higher Education Upgrading Plan(2021-2025)of“Rushing to the Top,Making Up Shortcomings and Strengthening Special Features”(R0400001-22)Additionally,we acknowledge support from the Zhuhai Basic and Applied Basic ResearchFoundation(2220004002717).
文摘CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.
文摘For nickel-based superalloys with medium volume-fractionγʹphase(20%-40%),dual or multi-stage aging treatments are usually conducted to generate a microstructure containing the multimodal distri-bution ofγʹfor a balance of strength and plasticity.In the present study,the microstructure and high-temperature properties of a novel cast nickel-based superalloy K4800 were investigated after being sub-jected to three heat treatments(HT)procedures,namely HT1:1180℃/4 h+1090℃/2 h+800℃/16 h,HT2:1180℃/4 h+1060℃/2 h+800℃/16 h and HT3:1180℃/4 h+800℃/16 h.It was found that the sub-solvus aging treatments at 1090 and 1060℃ precipitated sub-micron-sized(∼300 nm)primaryγʹphase which enhanced the ductility during 800℃ tensile(the total elongation of T1,T2,and T3 sam-ples were 6.75%,7.3%,and 3.25%,respectively)without evidently impairing the strength.After careful microstructure observation and deformation mechanism analysis,the enhancement of elongation was ra-tionalized that the precipitation of the sub-micron-sized primaryγʹphase decreased the volume-fraction and size of the nanometer-sizedγʹphase which was precipitated at 800℃,and simultaneously,pro-moted the dislocation movement by suppressing the non-planar slip.However,an excessive amount of the sub-micron-sized primaryγʹphase led to a faster ripening process of the nanometer-sizedγʹduring creep,which decreased the creep life at 800℃/430 MPa(T1:125 h,T2:199 h,and T3:198 h).Based on this,we monitored the number density of nanometer-sizedγʹphase coexisting with different amounts of largeγʹduring creep.An area fraction less than 7%of the sub-micron-sizedγʹphase was considered to have little detrimental effect on the creep life of K4800 alloy,which corresponded to a sub-solvus temperature range about 1080-1090℃.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010297)the National Natural Science Foundation of China(32100765)+1 种基金the Xiamen Medical Health Science and Technology Project(3502Z20194098)the Shenzhen-Hong Kong-Macao Science and Technology Innovation Project(SGDX2020110309280100).
文摘Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].
文摘Background: Cryptococcus neoformans is an opportunistic fungal pathogen that primarily affects immunocompromised individuals. While traditional histologic methods such as hematoxylin and eosin (H&E) staining can sometimes identify fungal organisms, definitive diagnosis typically requires microbiological culture or molecular testing. Stimulated Raman Histology (SRH) is an emerging imaging technology that enables rapid, label-free tissue analysis, potentially improving intraoperative diagnostic workflows. Aim: This case report explores the utility of SRH for the real-time identification of pulmonary cryptococcosis, highlighting its potential to enhance tissue triage and expedite diagnosis. Case Presentation: We report a 44-year-old man with a history of smoking and alcohol use who presented with a right lower lung mass. An ION robotic-assisted bronchoscopy was performed, and SRH was used intraoperatively for real-time tissue evaluation. Within approximately 90 seconds, SRH provided morphologic findings indicative of Cryptococcus neoformans, prompting additional microbiological testing, which confirmed the diagnosis. The patient required a six-week hospitalization with antifungal therapy. Conclusion: This case demonstrates the potential of SRH as a rapid, intraoperative diagnostic tool for detecting fungal infections in pulmonary specimens. By enabling real-time morphological assessment, SRH can optimize biopsy specimen triage, reduce the need for repeat procedures, and improve patient management. Integrating SRH into diagnostic workflows may be particularly beneficial in resource-limited settings, where timely cryptococcosis diagnosis is critical.
文摘Soft tissue tumors in the hand have a broad differential diagnosis. Included in the list of differential diagnoses for these tumors are Schwannomas, which are benign tumors within the peripheral nervous system [1]. Schwannomas are uncommon within the upper extremity, and they are exceedingly rare within the hand and wrist [1]. We describe a case of an 80-year-old female presented with a soft tissue mass within her right thumb. She underwent excisional biopsy of the mass, and pathology showed features consistent with schwannoma. She had resolution of her symptoms thereafter. We discuss the differential diagnosis for soft-tissue tumors in this location. When assessing patients with soft tissue tumors of the hand and wrist, it is important for the treating provider to maintain a broad differential diagnosis in order to facilitate appropriate management of these lesions.
文摘In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care floor and diagnosed with juvenile dermatomyositis and found to be positive for anti-Mi-2 alpha, anti-Mi-2 beta, and anti-MDA-5 antibodies. He gradually improved with a combination of steroid, immunomodulatory treatment, and physical therapy. This case outlines the clinical course of a patient with this rare disorder as well as the importance of understanding the role of associated antibodies to manage potential long-term sequelae.
基金National Natural Science Foundation of China,No.42371165,No.41872029。
文摘Situated in the semi-arid regions of North China,the Nihewan Basin documents the fluvio-lacustrine sequence and Pleistocene archaeological sites,offering an excellent opportunity to investigate human adaptation to environmental change in East Asia,especially in North China.However,paleoenvironmental datasets from Middle Pleistocene archaeological sites are not fully understood.Focusing on the evidence from the 0.63-0.49 Ma-old site of Jijiazhuang(Nihewan Basin,North China),this paper presents the results of various environmental indicators from the site context.Moreover,it explores the links between hominin behavioral adaptations and ecological variability during the extra-long interglacial period in North China.Sedimentological features of the excavated section indicate that the site was formed in the margin of the Nihewan paleolake.Based on well-constructed pollen,sediment grain size,color reflectance,and major geochemical element analyses,five stages of environmental changes were identified during site formation.This study indicates that hominins occupied the site at the early part of Stage 2,when the Nihewan paleolake had a relatively low water level and the climate was temperate,with strong weathering intensity dominated by wooded grassland landscapes.In conclusion,the results suggest that the extra-long duration of interglacial or mild stadial climate events(MISs 15-13)in the Northern Hemisphere may have provided favorable conditions for increased technological innovations and adaptive strategies among Middle Pleistocene hominins in the Nihewan Basin even in North China.
基金supported by the National Natural Science Foundation of China(Grant No.52403305)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0880000)+1 种基金Tianchi Talent Program of Xinjiang Uygur Autonomous Region(Grant No.2024000068)Postdoctoral Fellow-ship Program(Grade C)(Grant No.GZC20232959)。
文摘The prediction of new fluorooxoborates as ultraviolet(UV)/deep ultraviolet(DUV)opto-electronic functional materials from a largely unexplored chemical space is a challenging task.It has been suggested that the anionic frameworks formed by B–O and B–O–F units significantly determine the physical properties of fluorooxoborates.Therefore,the rational design of anionic frameworks could facilitate the materials discovery process.Herein,we propose that a candidate anionic framework can be efficiently derived from an existing one by slightly altering its oxygen content.Following this idea,we hypothesized the existence of a 1D[B_(3)O_(5)F]_(∞)chain from the wellknown 2D[B_(6)O_(9)F_(2_)]_(∞)layer.Accordingly,seven CaB_(3)O_(5)F structures with the expected anionic framework were successfully predicted.First-principles calculations show that all these structures have potential in the UV/DUV birefringent or nonlinear optical(NLO)material field,indicating that the 1D[B_(3)O_(5)F]_(∞)chain is indeed a promising anionic framework for achieving UV/DUV birefringent and NLO performance.
基金National Social Science Foundation of China,No.20FJLB025National Natural Science Foundation of China,No.42471207,No.42471203Zhejiang Province Philosophy and Social Science Planning,Zhijiang Youth Special Project,24ZJQN118Y。
文摘The effects of the built environment factors on urban vitality have attracted wide attention in the urban planning fields in recent years,but few studies have considered the variables’relative importance and their nonlinear effects on urban vitality.Taking a Chinese metropolis—Hangzhou as a case study,this study applied the gradient boosting decision tree(GBDT)model to explore the nonlinear effects of the 5D factors of the urban built environment on urban social vitality and economic vitality and the importance of variables.The results show that the GBDT model has better goodness of fit than the traditional ordinary least squares(OLS)regression in the urban vitality models.The urban built environment plays an important role in affecting urban vitality,while built environment designs witness the most important effect.Specifically,the density of shopping facilities,medical facilities,and road networks are the most important factors affecting urban social vitality,while road network density,destination accessibility,and population density play the most important roles in affecting urban economic vitality.Finally,the urban built environment factors have nonlinear threshold effects on both urban economic and social vitality in Hangzhou,with differing nonlinear response patterns observed between social and economic dimensions.
基金funded by the CAS“Light of West China”Program(grant Nos.2021-XBQNXZ-030 and 2021-XBQNXZ-005)the Xinjiang Key Laboratory of Radio Astrophysics(grant No.2023D04064)the National Key R&D Program of China(grant No.2024YFA1611503)。
文摘Accurate estimation of Zenith Tropospheric Delay(ZTD)is essential for mitigating atmospheric effects in radio astronomical observations and improving the retrieval of precipitable water vapor(PWV).In this study,we first analyze the periodic characteristics of ZTD at the NanShan Radio Telescope site using Fourier transform,revealing its dominant seasonal variations,and then investigate the correlation between ZTD and local meteorological parameters,to better understand atmospheric influences on tropospheric delay.Based on these analyses,we propose a hybrid deep learning Gated Recurrent Units-Long Short-Term Memory model,incorporating meteorological parameters as external inputs to enhance ZTD forecasting accuracy.Experimental results demonstrate that the proposed approach achieves a Root Mean Squared Error of 7.97 mm and a correlation coefficient R of 96%,significantly outperforming traditional empirical models and standalone deep learning architectures.These findings indicate that the model effectively captures both short-term dynamics and long-term dependencies in ZTD variations.The improved ZTD predictions not only contribute to reducing atmospheric errors in radio astronomical observations but also provide a more reliable basis for PWV retrieval and forecasting.This study highlights the potential of deep learning in tropospheric delay modeling,offering advancements in both atmospheric science and geodetic applications.
文摘In the last two decades,seismic resilience(SR)has been developed as a main concept for the assessment of the structural vulnerabilities of buildings and city centres.In particular,historical centers consist of adjacent buildings organized in blocks with common characteristics and similar typologies.The paper proposes a meth-odology to quantify SR for urban regions,by overcoming the state of the art studies that focus on assessing the SR for singular buildings.In this regard,the presented methodology may calculate the SR of blocks of buildings for the assessment of recovery investments of historical city centers.The main idea is to assess the level of vulnerability by accurate 3D surveys and visual inspections in order to select empirical fragility curves.The proposed methodology was herein applied to the city center of San Marino,designated by UNESCO as a world heritage site.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China(Grant Nos.2019YFC1803500,2019YFC1803504)the Key R&D Projects of Sichuan Provincial Science and Technology Department(Grant Nos.2018SZ0298,2023YFS0390)+1 种基金the Bureau of Science and Technology Aba Qiang Tibetan Autonomous Prefecture(Grant Nos.R22YYJSYJ0004,R23YYJSYJ0010)Southwest University of Science and Technology Doctoral Program(23zx7175)。
文摘Scale effects and evaluation models are crucial to the accuracy of landscape ecological risk evaluation.However,most studies conduct these evaluations at a single scale or with a single model,ignoring potential scale effects and changes in landscape patterns.To address this,we took the Leshan City in Sichuan Province of China as a study case.We determined that the optimal spatial granularity for the study area is 150 m by analyzing the sensitivities of eight landscape pattern indices such as landscape fragmentation,landscape spreading,and Shannon's diversity at different spatial granularities,and employing the inflection point identification method.Building on this,we constructed a landscape pattern index model(ERI model)and a landscape pattern index model coupled with the ecological process of soil erosion(SI-ERI model)by incorporating the natural geographic factors of the study area.We used the ERI and SI-ERI models to evaluate the landscape ecological risk of Leshan City across multiple scales,including ecological,administrative,and sample scales.After conducting overlay and spatial autocorrelation analyses of the multi-scale evaluation results,we determined that the administrative scale is optimal for evaluating landscape ecological risk in the study area.At this scale,we verified the accuracy and reliability of the two models'evaluation results against the actual ecological environment in typical areas within the study area.The findings indicated that the SI-ERI model provided more precise and accurate spatial characterization,effectively reflecting the actual landscape ecological risk of Leshan City.According to the SI-ERI model's evaluation results at the administrative scale,Leshan City's overall risk level is relatively low,with good ecological environmental quality.Low-risk areas constitute 56.16%and medium-low-risk areas make up 23.81%,aligning closely with the city's actual situation.This study thus offers a scientific basis and theoretical reference for managing ecological risks and planning urban development in Leshan City.
文摘Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer （mCRPC）. The past year and a half has been marked by unprecedented progress in treatments for this disease. Three positive phase III clinical trials have emerged, each evaluating agents （sipuleuceI-T, cabazitaxel and abiraterone） with distinct mechanisms of action. Herein, the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC. The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past. We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome. The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.
基金financially supported by the National Natural Science Foundation of China(No.32172855)Fundamental Research Funds for the Central Universities(Nos.2632024ZD07,2632024TD02)the Open Project of Jiangsu Provincial Science and Technology Resources(Clinical Resources)Coordination Service Platform(No.TC2023B001)。
文摘The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the clinical treatment of bacterial meningitis challenging.Herein,a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis,to overcome the low drug concentration and drug resistance.This strategy was achieved by a proteinsupported Au nanozyme(ANZ).With a particle size of less than 10 nm,it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H_(2)O_(2).Benefiting from the cascade catalytic amplification effect generated by its dual enzymelike activities,ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro.Notably,small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration.In a mouse model of bacterial meningitis,the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone.Additionally,the meningitis mice exhibited undamaged cognitive and behavioral abilities,indicating the excellent biocompatibility of ANZ.The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation,strong antibacterial efficacy and does not lead to bacterial resistance.It holds broad prospects for the treatment of bacterial meningitis.
基金Strategic Priority Research Programs of the Chinese Academy of Sciences,Grant/Award Number:XDA19050301National Natural Science Foundation of China,Grant/Award Number:31601189,81572433 and 81772646+1 种基金Biological Resources Program from Chinese Academy of Sciencesthe Young Elite Scientist Sponsorship Program by CAST,Grant/Award Number:2018QNRC001
文摘CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been developed into a series of powerful gene‐editing tools. As the natural inhibitors of CRISPR‐Cas systems, anti‐CRISPRs (Acrs) can be used as the “off‐switch” for CRISPR‐Cas systems to limit the off‐target effects caused by Cas9. Since the discovery of CRISPR‐Cas systems, much research has focused on the identification, mechanisms and applications of Acrs. In light of the rapid development and scientific significance of this field, this review summarizes the history and research status of Acrs, and considers future applications.
