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Abstract Background Catheter-related thrombosis (CRT) is a thrombotic complication associated with using central venous catheters (CVCs). Although risk factors for CRT were identified in children, no nomograms or predictive tools are available for the pediatric population with CVCs. This study aimed to develop and validate a prediction model of asymptomatic CRT in children with CVCs. Methods This retrospective observational study included consecutive pediatric patients who admitted to the Children’s Hospital Zhejiang University School of Medicine and received CVCs between October and December 2021. Results This study included 669 patients, 553 (314 males, aged 22.00 [0.36, 180.00] months, 62 with CRT) were in the training set, and 116 (62 males, aged 15.00 [1.13, 156.00] months, 16 with CRT) were in the validation set. Multivariate logistic regression showed that a catheter time of 0–3 days (OR = 0.201, 95%CI: 0.081–0.497, P = 0.001), catheter time of 4–7 days (OR = 0.412, 95%CI: 0.176–0.964, P = 0.041), male (OR = 3.976, 95%CI: 1.864–4.483, P

Abstract Background China’s family planning policies have experienced stages of one-child policy, partial two-child policy, and universal two-child policy. However, the impact of these policy shifts on the spatial accessibility to maternal and child health (MCH) services for women and children remains uncertain. This study aimed to evaluate the spatiotemporal trends and geographic disparities in spatial accessibility to MCH services in the context of two-child polices. Methods This study was conducted in Nanning prefecture, China, from 2013 to 2019. Data on the transportation networks, MCH institutes, the annual number of newborns, and the annual number of pregnant women in Nanning prefecture were collected. Gaussian two-step floating catchment area (Ga2SFCA) method was employed to measure the spatial accessibility to MCH services at county, township, and village levels. Temporal trends in spatial accessibility were analyzed using Joinpoint regression analysis. Geographic disparities in spatial accessibility were identified using geographic information system (GIS) mapping techniques. Results Overall, the spatial accessibility to MCH services showed an upward trend from 2013 to 2019 at county, town, and village levels, with the average annual percent change (AAPC) being 5.04, 4.73, and 5.39, respectively. Specifically, the spatial accessibility experienced a slight downward trend during the period of partial two-child policy for both parents only children (i.e., 2013–2014), a slight upward trend during the period of partial two-child policy for either parent only child (i.e., 2014–2016) and the early stages of universal two-child policy (i.e., 2016–2018), and a large upward trend in the later stages of universal two-child policy (i.e., 2018–2019). Spatial accessibility to MCH services gradually decreased from central urban areas to surrounding rural areas. Regions with low spatial accessibility were predominantly located in remote rural areas. Conclusion With the gradual opening of the two-child policies, the spatial accessibility to MCH services for women and children has generally improved. However, significant geographic disparities have persisted throughout the stages of the two-child policies. Comprehensive measures should be considered to improve equity in MCH services for women and children.

Abstract Background Education is an important part of the work of most doctors. Clinical preceptors act as role models and supervisors. Preceptors’ quality of supervision strongly influences the learning quality of clinical interns (Bartlett et al. BMC Med Educ 20:165, 2020). To ensure a consistent approach to every preceptorship experience, the competency of clinical preceptors should be assessed to ensure that the desired outcomes are achieved. This study aims to evaluate clinical preceptors’ competency in learner-centered teaching, to provide constructive feedback to develop the preceptors’ competency and improve supervisory skills and internship quality at Kunming Medical University (KMU) in Kunming of China. Methods This is a cross-sectional study with a quantitative self-administered online questionnaire. The convenience sampling technique was employed. In the undergraduate internship stage of KMU, clinical preceptors (N = 340) and interns (N = 487) were invited to use the augmented Stanford Faculty Development Program questionnaire (SFDPQ) (Stalmeijer et al. Med Teach 30:e272–e277, 2008), to (self-) assess the preceptor’s competency of learner-centered teaching on a five-point scale (1 = strongly disagree, 5 = strongly agree). Results Two hundred twenty-eight preceptors and two hundred thirty-six interns completed the questionnaire correctly. Overall, the assessment was positive, but the preceptors’ self-assessment significantly higher than the interns’ (p

Reservoir-induced earthquakes (RIEs) occur frequently in the Three Gorges Reservoir Area (TGRA) and the rock mass strength of the hydro-fluctuation belt (HFB) deteriorates severely due to the reservoir-induced seismic loads. Three models of typical bedded rock slopes (BRSs), i.e. gently (GIS), moderately (MIS), and steeply (SIS) inclined slopes, were proposed according to field investigations. The dynamic response mechanism and stability of the BRSs, affected by the rock mass deterioration of the HFB, were investigated by the shaking table test and the universal distinct element code (UDEC) simulation. Specifically, the amplification coefficient of the peak ground acceleration (PGA) of the slope was gradually attenuated under multiple seismic loads, and the acceleration response showed obvious “surface effect” and “elevation effect” in the horizontal and vertical directions, respectively. The “S-type” cubic function and “steep-rise type” exponential function were used to characterize the cumulative damage evolution of the slope caused by microseismic waves (low seismic waves) and high seismic waves, respectively. According to the dynamic responses of the acceleration, cumulative displacement, rock pressure, pore water pressure, damping ratio, natural frequency, stability coefficient, and sliding velocity of the slope, the typical evolution processes of the dynamic cumulative damage and instability failure of the slope were generalized, and the numerical and experimental results were compared. Considering the dynamic effects of the slope height (SH), slope angle (SA), bedding plane thickness (BPT), dip angle of the bedding plane (DABP), dynamic load amplitude (DLA), dynamic load frequency (DLF), height of water level of the hydro-fluctuation belt (HWLHFB), degradation range of the hydro-fluctuation belt (DRHFB), and degradation shape of the hydro-fluctuation belt (DSHFB), the sensitivity of factors influencing the slope dynamic stability using the orthogonal analysis method (OAM) was DLA > DRHFB > SA > SH > DLF > HWLHFB > DSHFB > DABP > BPT.

Abstract Background Radiotherapy can modulate systemic antitumor immunity, while immune status in the tumor microenvironment also influences the efficacy of radiotherapy, but relevant molecular mechanisms are poorly understood in lung adenocarcinoma (LUAD). Methods In this study, we innovatively proposed a radiotherapy response classification for LUAD, and discovered ESYT3 served as a tumor suppressor and radioimmune response sensitizer. ESYT3 expression was measured both in radioresistant and radiosensitive LUAD tissues and cells. The influence of ESYT3 on radiotherapy sensitivity and resistance was then investigated. Interaction between ESYT3 and STING was evaluated through multiple immunofluorescent staining and coimmunoprecipitation, and downstream molecules were further analyzed. In vivo models were constructed to assess the combination treatment efficacy of ESYT3 overexpression with radiotherapy. Results We found that radioresistant subtype presented immunosuppressive state and activation of DNA damage repair pathways than radiosensitive subtype. ESYT3 expression was remarkably attenuated both in radioresistant LUAD tissues and cells. Clinically, low ESYT3 expression was linked with radioresistance. Overexpression of ESYT3 enabled to alleviate radioresistance, and sensitize LUAD cells to DNA damage induced by irradiation. Mechanically, ESYT3 directly interacted with STING, and activated cGAS-STING signaling, subsequently increasing the generation of type I IFNs as well as downstream chemokines CCL5 and CXCL10, thus improving radioimmune responses. The combination treatment of ESYT3 overexpression with radiotherapy had a synergistic anticancer effect in vitro and in vivo. Conclusions In summary, low ESYT3 expression confers resistance to radiotherapy in LUAD, and its overexpression can improve radioimmune responses through activating cGAS-STING-dependent pathway, thus providing an alternative combination therapeutic strategy for LUAD patients.

Abstract A solar home system (SHS), containing three independent parts, namely a load voltage dc–dc converter, an energy storage device (ESD) charger, and an ESD equalizer, will become bulky and costly. Thus, based on Cuk converter, an integrated charging equalizing converter (ICEC) is proposed. The ICEC can achieve load voltage converting, battery/supercapacitor (SC) charging, and equalizing simultaneously. The idea of the ICEC is using a voltage multiplier (VM) to replace the capacitor in Cuk convertor, and then reusing the VM as a charging equalizer. When the Cuk converter is operating, the voltage ripple generated on the VM, which can be regarded as an ac voltage source, is utilized to drive the VM. Therefore, compared with the traditional methods, the charging and equalizing can be achieved without extra switches and magnetic elements. A prototype for four SCs is built to verify the feasibility of the proposed method. And the system efficiency is 87%, corresponding to the input power 5.6 W, the load output power 3.54 W, and the charging balance power 1.33 W. Moreover, a quantitative comparison shows the proposed method can reduce the system size and cost effectively.

In this study, the 16 mm thick aluminum alloy was successfully welded using variable polarity plasma arc (VPPA) keyhole welding. The microstructure and microhardness distributions of the weld were systematically measured along its thickness and width. To evaluate tensile strengths along the weld thickness, tensile specimens were divided into upper, middle, and lower sections. The surface temperature distribution of the weld pool, along with the temperature profile through its thickness, was measured using thermometers and thermocouples. Numerical simulations were employed to calculate the pressure oscillations along the keyhole boundary and to analyze the temperature and flow field distributions of the VPPA. The findings initially revealed a homogeneous and refined microstructure distribution within the weld seam. The weld zone exhibited higher microhardness compared to the base metal (BM). The weld demonstrated a tensile strength of 187.86 MPa and an elongation of 24.76%, corresponding to 95.57% and 78.65% of the BM, respectively. The tensile strengths and elongations of the upper, middle, and lower sections displayed a similar distribution to that of the entire weld. The mechanism underlying the microstructure distribution of the weld was significantly influenced by the temperature distribution of the weld pool, dynamic pressure oscillations in the mushy zone, and fluid flow of the weld pool. Specifically, the mechanism whereby pressure oscillations fracture existing nuclei and generate multiple new nuclei has been proposed to explain the refined microstructure distribution. These findings provide crucial insights for optimizing VPPA keyhole welding technology, ensuring stable and high-quality welding of thick aluminum alloys.

Abstract Ducted-fan drones are expected to become the main drone configuration in the future due to their high efficiency and minimal noise. When drones operate in confined spaces, significant proximity effects may interfere with the aerodynamic performance and pose challenges to flight safety. This study utilizes computational fluid dynamics simulation with the Unsteady Reynolds-averaged Navier–Stokes (URANS) method to estimate the proximity effects. Through experimental validation, our computational results show that the influence range of proximity effects lies within four rotor radii. The ground effect and the ceiling effect mainly affect thrust properties, while the wall effect mainly affects the lateral force and the pitching moment. In ground effect, the rotor thrust increases exponentially by up to 26% with ground distance compared with that in open space. Minimum duct thrust and total thrust are observed at one rotor radius above the ground. In ceiling effect, all the thrusts rise as the drone approaches the ceiling, and total thrust increases by up to 19%. In wall effect, all the thrusts stay constant. The pitching moment and lateral force rise exponentially with the wall distance. Changes in blade angle of attack and duct pressure distributions can account for the performance change. The results are of great importance to the path planning and flight controller design of ducted-fan drones for safe and efficient operations in confined environments.

A Co-free non-equiatomic Ni2·5CrFeAl0·25Ti0.25 medium-entropy alloy (MEA) with an excellent strength-ductility synergy was fabricated, which shows a multiphase structure composed of face-centered cubic (FCC), L12 (ordered FCC), and Cr-rich body-centered cubic (BCC) phase by thermomechanical processing. Specifically, the aged sample displays the outstanding yield tensile strength (YTS, ∼1188 MPa), ultimate tensile strength (UTS, ∼1560 MPa) and work-hardening rate (WHR, ∼4.5 GPa) values as well as an acceptable plasticity of ∼16.6%. Theoretical calculations suggest that precipitation strengthening significantly contributes to achieving the fascinating tensile strength among various strengthening contributors. Further analyses reveal that multiple nanoscale stacking-fault (SF) networks are activated during plastic deformation in the aged alloy. Accordingly, the dual effects consisting of the hierarchical precipitation structure and SF networks lead to the combination of excellent tensile strength and strain-hardening capacity.

Abstract Antiferromagnets have attracted significant attention in the field of magnonics, as promising candidates for ultralow-energy carriers for information transfer for future computing. The role of crystalline orientation distribution on magnon transport has received very little attention. In multiferroics such as BiFeO3 the coupling between antiferromagnetic and polar order imposes yet another boundary condition on spin transport. Thus, understanding the fundamentals of spin transport in such systems requires a single domain, a single crystal. We show that through Lanthanum (La) substitution, a single ferroelectric domain can be engineered with a stable, single-variant spin cycloid, controllable by an electric field. The spin transport in such a single domain displays a strong anisotropy, arising from the underlying spin cycloid lattice. Our work shows a pathway to understanding the fundamental origins of magnon transport in such a single domain multiferroic.

Abstract NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

Abstract Background With a considerable variety of cancer subtypes, Non-small cell lung cancer (NSCLC) poses a substantial threat to public health, affecting a large number of individuals and resulting in a high mortality rate. Circular RNA (circRNA) has been applied in various diseases, including cancers. This study aims to investigate the clinial significance and functional role of circPTP4A2 in NSCLC. Methods The serum and tissue samples were collected for detecting circPTP4A2 expression in NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Actinomycin D was used to treat NSCLC cells to detect circPTP4A2 stability. The CCK-8 and Transwell assays were utilized to assess the effects of circPTP4A2 in NSCLC cells. The ELISA assay and cytotoxicity analysis were used to detect the roles of circPTP4A2 in immune escape. Results The serum and tissue circPTP4A2 expression was upregulated in NSCLC. The high circPTP4A2 had a relatively high value in differentiating NSCLC patients from healthy individuals. The proliferation, invasion, and immune escape were repressed by circPTP4A2 knockdown. Conclusions High circPTP4A2 has the potential to be a diagnostic biomarker in NSCLC. Silencing of circPTP4A2 receded the progression of NSCLC and enhanced antitumor immunity, which might provide potential targets and new ideas for improving the diagnosis and effect of immunotherapy in NSCLC patients.

Abstract Reducing interface nonradiative recombination is important for realizing highly efficient perovskite solar cells. In this work, we develop a synergistic bimolecular interlayer (SBI) strategy via 4-methoxyphenylphosphonic acid (MPA) and 2-phenylethylammonium iodide (PEAI) to functionalize the perovskite interface. MPA induces an in-situ chemical reaction at the perovskite surface via forming strong P-O-Pb covalent bonds that diminish the surface defect density and upshift the surface Fermi level. PEAI further creates an additional negative surface dipole so that a more n-type perovskite surface is constructed, which enhances electron extraction at the top interface. With this cooperative surface treatment, we greatly minimize interface nonradiative recombination through both enhanced defect passivation and improved energetics. The resulting p-i-n device achieves a stabilized power conversion efficiency of 25.53% and one of the smallest nonradiative recombination induced V oc loss of only 59 mV reported to date. We also obtain a certified efficiency of 25.05%. This work sheds light on the synergistic interface engineering for further improvement of perovskite solar cells.

Abstract Background This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations. Methods A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2. Results The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality. Conclusion Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.

Abstract NOTCH receptor 3 (NOTCH3) is known to regulate the transcription of oncogenes or tumor suppressor genes, thereby playing a crucial role in tumor development, invasion, maintenance, and chemotherapy resistance. However, the specific mechanism of how NOTCH3 drives immune infiltration in gastrointestinal cancer remains uncertain. The expression of NOTCH3 was analyzed through Western blot, PCR, Oncomine database, and the Tumor Immune Estimation Resource (TIMER) site. Kaplan–Meier plotter, PrognoScan database, and gene expression profile interactive analysis (GEPIA) were used to assess the impact of NOTCH3 on clinical prognosis. The correlation between NOTCH3 expression and immune infiltration gene markers was investigated using TIMER and GEPIA. NOTCH3 was found to be commonly overexpressed in various types of gastrointestinal tumors and was significantly associated with poor prognosis. Furthermore, the expression level of NOTCH3 showed a significant correlation with the tumor purity of gastrointestinal tumors and the extent of immune infiltration by different immune cells. Our findings suggest that NOTCH3 may act as a crucial regulator of tumor immune cell infiltration and can serve as a valuable prognostic biomarker in gastrointestinal cancers.

Abstract Background About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response. Methods This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal. Results PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy. Conclusion PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

Abstract Efficient charge-carrier injection and transport in organic light-emitting devices (OLEDs) are essential to simultaneously achieving their high efficiency and long-term stability. However, the charge-transporting layers (CTLs) deposited by various vapor or solution processes are usually in amorphous forms, and their low charge-carrier mobilities, defect-induced high trap densities and inhomogeneous thickness with rough surface morphologies have been obstacles towards high-performance devices. Here, organic single-crystalline (SC) films were employed as the hole-transporting layers (HTLs) instead of the conventional amorphous films to fabricate highly efficient and stable OLEDs. The high-mobility and ultrasmooth morphology of the SC-HTLs facilitate superior interfacial characteristics of both HTL/electrode and HTL/emissive layer interfaces, resulting in a high Haacke’s figure of merit (FoM) of the ultrathin top electrode and low series-resistance joule-heat loss ratio of the SC-OLEDs. Moreover, the thick and compact SC-HTL can function as a barrier layer against moisture and oxygen permeation. As a result, the SC-OLEDs show much improved efficiency and stability compared to the OLEDs based on amorphous or polycrystalline HTLs, suggesting a new strategy to developing advanced OLEDs with high efficiency and high stability.

Freshwater salinization is receiving increasing global attention due to its profound influence on nitrogen cycling in aquatic ecosystems and the accessibility of water resources. However, a comprehensive understanding of the changes in river salinization and the impacts of salinity on nitrogen cycling in arid and semi-arid regions of China is currently lacking. A meta-analysis was first conducted based on previous investigations and found an intensification in river salinization that altered hydrochemical characteristics. To further analyze the impact of salinity on nitrogen metabolism processes, we evaluated rivers with long-term salinity gradients based on in situ observations. The genes and enzymes that were inhibited generally by salinity, especially those involved in nitrogen fixation and nitrification, showed low abundances in three salinity levels. The abundance of genes and enzymes with denitrification and dissimilatory nitrate reduction to ammonium functions still maintained a high proportion, especially for denitrification genes/enzymes that were enriched under medium salinity. Denitrifying bacteria exhibited various relationships with salinity, while dissimilatory nitrate reduction to ammonium bacterium (such as Hydrogenophaga and Curvibacter carrying nirB) were more inhibited by salinity, indicating that diverse denitrifying bacteria could be used to regulate nitrogen concentration. Most genera exhibited symbiotic and mutual relationships, and the highest proportion of significant positive correlations of abundant genera was found under medium salinity. This study emphasizes the role of river salinity on environment characteristics and nitrogen transformation rules, and our results are useful for improving the availability of river water resources in arid and semi-arid regions.

Abstract Background Circular RNAs (circRNAs), which are a new type of single-stranded circular RNA, have significant involvement in progression of many diseases, including tumors. Currently, multiple circRNAs have been identified in hepatocellular carcinoma (HCC). Our study aims to investigate the function and mechanism of circDCAF8 in HCC. Methods The expression of circDCAF8 (hsa_circ_0014879) in HCC and para-carcinoma tissue samples was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The biological function of circDCAF8 in HCC was confirmed by experiments conducted both in vitro and in vivo. And the relationship between circDCAF8, miR-217 and NAP1L1 was predicted by database and verified using qRT-PCR, RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Exosomes isolated from HCC cells were utilized to assess the connection of exosomal circDCAF8 with HCC angiogenesis and regorafenib resistance. Results CircDCAF8 is upregulated in HCC tissues and cell lines, and is linked to an unfavourable prognosis for HCC patients. Functionally, circDCAF8 was proved to facilitate proliferation, migration, invasion and Epithelial-Mesenchymal Transformation (EMT) in HCC cells. Animal examinations also validated the tumor-promoting characteristics of circDCAF8 on HCC. Besides, exosomal circDCAF8 promoted angiogenesis in HUVECs. Mechanistically, circDCAF8 interacted with miR-217 and NAP1L1 was a downstream protein of miR-217. CircDCAF8 promoted NAP1L1 expression by sponging miR-217. In addition, exosomes may transfer circDCAF8 from regorafenib-resistant HCC cells to sensitive cells, where it would confer a resistant phenotype. Conclusion CircDCAF8 facilitates HCC proliferation and metastasis via the miR-217/NAP1L1 axis. Meanwhile, circDCAF8 can promote angiogenesis and drive resistance to regorafenib, making it a viable therapeutic target for HCC patients.

Abstract Background Relative handgrip strength (RHGS) was positively correlated with healthy levels of cardiovascular markers and negatively correlated with metabolic disease risk. However, its association with hyperlipidemia remains unknown. The present study investigated the link between RHGS and hyperlipidemia, utilizing data from the National Health and Nutrition Examination Survey (NHANES) and further examined the hypothesis that inflammation may serve a mediating role within this relationship. Methods Data were extracted from 4610 participants in the NHANES database spanning 2011–2014 to explore the correlation between RHGS and hyperlipidemia using multivariate logistic regression models. Subgroup analyses were conducted to discern the correlation between RHGS and hyperlipidemia across diverse populations. Additionally, smooth curve fitting and threshold effect analysis were conducted to validate the association between RHGS and hyperlipidemia. Furthermore, the potential mediating effect of inflammation on this association was also explored. Results According to the fully adjusted model, RHGS was negatively correlated with hyperlipidemia [odds ratio (OR) = 0.575, 95% confidence interval (CI) = 0.515 to 0.643], which was consistently significant across all populations, notably among women. Smooth curve fitting and threshold effect analysis substantiated the negative association between RHGS and hyperlipidemia. Moreover, the mediating effects analysis indicated the white blood cell (WBC) count, neutrophil (Neu) count, and lymphocyte (Lym) count played roles as the mediators, with mediation ratios of 7.0%, 4.3%, and 5.0%, respectively. Conclusions This study identified a prominent negative correlation between RHGS and hyperlipidemia. Elevated RHGS may serve as a protective factor against hyperlipidemia, potentially through mechanisms underlying the modulation of inflammatory processes.

Abstract Background Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. Results Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. Conclusion Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics.

Abstract Light-induced spin currents with the faster response is essential for the more efficient information transmission and processing. Herein, we systematically explore the effect of light illumination energy and direction on the light-induced spin currents in the W/Y3Fe5O12 heterojunction. Light-induced spin currents can be clearly categorized into two types. One is excited by the low light intensity, which mainly involves the photo-generated spin current from spin photovoltaic effect. The other is caused by the high light intensity, which is the light-thermally induced spin current and mainly excited by spin Seebeck effect. Under low light-intensity illumination, light-thermally induced temperature gradient is very small so that spin Seebeck effect can be neglected. Furthermore, the mechanism on spin photovoltaic effect is fully elucidated, where the photo-generated spin current in Y3Fe5O12 mainly originates from the process of spin precession induced by photons. These findings provide some deep insights into the origin of light-induced spin current.

Abstract Background Insulin resistance (IR) significantly contributes to cardiovascular disease (CVD) development. Triglyceride glucose (TyG) index and triglyceride glucose-body mass index (TyG-BMI) are recognised as convenient proxies for IR. However, their relationship with sudden cardiac arrest (SCA) remains unclear. Methods This prospective cohort analysis included 355,242 UK Biobank participants with available TyG index and TyG-BMI data and no history of CVD. Cox proportional risk models assessed the association between the TyG index, TyG-BMI and SCA risk. Additionally, Accelerated Failure Time (AFT) models were employed to investigate the timing of SCA onset. The impact of dynamic increases in TyG index and TyG-BMI levels on SCA risk was examined using restricted cubic spline. Results Over a median follow-up period of 165.4 months (interquartile range 156.5–174 months), 1,622 cases of SCA were recorded. Multivariate Cox regression analysis revealed a 9% increase in SCA risk per standard deviation increase in TyG index (adjusted hazard ratio (aHR) = 1.09, 95% confidence interval (CI) 1.04–1.15) and an 14% increase per standard deviation increase in TyG-BMI (aHR 1.14, 95% CI 1.09–1.2). AFT models indicated earlier median times to SCA occurrence with increasing quintiles of TyG index and TyG-BMI compared to the lowest quintile (P for trend

Abstract Background In bypass surgery for moyamoya disease (MMD), the superficial temporal artery’s (STA) pressure needs to surpass that of the cortical M4 recipient of the middle cerebral artery (MCA), boosting cerebral blood flow into the MCA and enhancing cerebral circulation. This study investigates the STA-MCA arterial pressure parameters and gradients during bypass surgery, aiming to deepen our understanding of hemodynamic shifts pre- and post-operation. Methods DSA imaging data were prospectively collected from patients diagnosed with bilateral MMD who underwent STA-MCA bypass surgery between 2022 and 2023 and stratified according to the Suzuki stage. The mean arterial pressure (MAP) of the donor and recipient arteries was directly measured during the STA-MCA bypass procedure, and these data were statistically analyzed and evaluated. Results Among 48 MMD patients, Suzuki grading revealed that 43.8% were in early stages (II and III), while 56.2% were in advanced stages (IV, V, and VI). Predominantly, 77.1% presented with ischemic-type MMD and 22.9% with hemorrhagic type. Pre-bypass assessments showed that 62.5% exhibited antegrade blood flow direction, and 37.5% had retrograde. The mean recipient artery pressure was 35.0 ± 2.3 mmHg, with a mean donor-recipient pressure gradient (δP) of 46.4 ± 2.5 mmHg between donor and recipient arteries. Post-bypass, mean recipient artery pressure increased to 73.3 ± 1.6 mmHg. No significant correlation (r = 0.18, P = 0.21) was noted between δP and Suzuki staging. Conclusion Our study elucidated that cerebral blood pressure significantly decreases beyond the moyamoya network at the distal M4 segment. Furthermore, we observed bidirectional flow in MCA territories and a significant positive pressure gradient between the STA and M4 segments. The lack of correlation between Suzuki stages and M4 pressures indicates that angiographic severity may not reflect hemodynamic conditions before surgery, highlighting the need for customized surgical approaches.

Abstract Background With the accumulating omics data, an efficient and time-saving transient assay to express target genes is desired. Mesophyll protoplasts, maintaining most stress-physiological responses and cellular activities as intact plants, offer an alternative transient assay to study target genes’ effects on heat and oxidative stress responses. Results In this study, a perennial ryegrass (Lolium perenne L.) mesophyll protoplast-based assay was established to effectively over- or down-regulate target genes. The relative expression levels of the target genes could be quantified using RT-qPCR, and the effects of heat and H2O2-induced oxidative stress on protoplasts’ viability could be quantitatively measured. The practicality of the assay was demonstrated by identifying the potential thermos-sensor genes LpTT3.1/LpTT3.2 in ryegrass that over-expressing these genes significantly altered protoplasts’ viability rates after heat stress. Conclusion This protoplast-based rapid stress regulatory gene identification assay was briefed as ‘PRIDA’ that will complement the stable genetic transformation studies to rapidly identify candidate stress-regulatory genes in perennial ryegrass and other grass species.

Abstract PbZrO3 has been broadly considered as a prototypical antiferroelectric material for high-power energy storage. A recent theoretical study suggests that the ground state of PbZrO3 is threefold-modulated ferrielectric, which challenges the generally accepted antiferroelectric configuration. However, such a novel ferrielectric phase was predicted only to be accessible at low temperatures. Here, we successfully achieve the room-temperature construction of the strongly competing ferrielectric and antiferroelectric state by strain-mediated phase separation in PbZrO3/SrTiO3 thin film. We demonstrate that the phase separation occurs spontaneously in quasi-periodic stripe-like patterns under a compressive misfit strain and can be tailored by varying the film thickness. The ferrielectric phase strikingly exhibitsa threefold modulation period with a nearly up-up-down configuration, which could be stabilized and manipulated by the formation and evolution of interfacial defects under applied strain. The present results construct a fertile ground for further exploring the physical properties and applications based on the novel ferrielectric phase.

Abstract The authors presents a low‐profile wideband circularly polarised (CP) millimetre‐wave (mmWave) elliptical integrated lens antenna (ILA) fabricated by dielectric 3D printing technology. The proposed lens is integrated with a dielectric polariser and an air cavity for phase compensation, which can transfer incident waves from linearly polarised (LP) to planar CP waves over a wide bandwidth. Compared to the classic bifocal ILA, the proposed lens has a low profile. The phase compensation is performed by introducing a specifically shaped air cavity, which greatly reduces the length and weight of the lens. The polariser causes the two electric field components Ex and Ey to degenerate with an orthogonal phase difference, which results in the wideband characteristics of the antenna. The polariser, air cavity and lens can be conveniently and precisely fabricated by low‐cost 3D printing technology. Measurements show that the proposed ILA has a wide axial ratio (AR) bandwidth of 21.9–32.6 GHz, while the gain reaches 22.54 dBic with a 38% size reduction and a 60.7% weight reduction. Benefiting from the low profile, high gain, wide bandwidth and low cost, the proposed ILA has great potential to be the candidate antenna for 5G applications and satellite communications.

Abstract Background Curcubita ficifolia Bouché (Cucurbitaceae) has high value as a food crop and medicinal plant, and also has horticultural value as rootstock for other melon species. China is home to many different cultivars, but the genetic diversity of these resources and the evolutionary relationships among them, as well as the differences between C. ficifolia and other Cucurbita species, remain unclear. Results We investigated the chloroplast (cp) genomes of 160 C. ficifolia individuals from 31 populations in Yunnan, a major C. ficifolia production area in China. We found that the cp genome of C. ficifolia is ~151 kb and contains 128 genes, of which 86 are protein coding genes, 34 encode tRNA, and eight encode rRNAs. We also identified 64 SSRs, mainly AT repeats. The cp genome was found to contain a total of 204 SNP and 57 indels, and a total of 21 haplotypes were found in the 160 study individuals. The reverse repeat (IR) region of C. ficifolia contained a few differences compared with this region in the six other Cucurbita species. Sequence difference analysis demonstrated that most of the variable regions were concentrated in the single copy (SC) region. Moreover, the sequences of the coding regions were found to be more similar among species than those of the non-coding regions. The phylogenies reconstructed from the cp genomes of 61 representative species of Cucurbitaceae reflected the currently accepted classification, in which C. ficifolia is sister to the other Cucurbita species, however, different interspecific relationships were found between Cucurbita species. Conclusions These results will be valuable in the classification of C. ficifolia genetic resources and will contribute to our understanding of evolutionary relationships within the genus Cucurbita.

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Abstract Background There are many difficulties in the reduction and fixation of the tibial plateau fractures involving posterolateral quadrant using general plates via traditional approaches. By imaging the area above the fibulae capitulum, this study was performed to investigate the feasibility of the trans-fibular-head approach and to design an ideal anatomical plate. Methods MRI and CT scans of the knee joint were collected from 205 healthy volunteers (103 males, 102 females). Gender and height were used to divide the volunteers into groups separately: (1) A1 group and A2 group according to gender, (2) B1 group and B2 group according to height. Based on the images, several parameters were defined and measured to describe the space above the head of the fibula. In addition, differences in these parameters between genders and height were compared. Results The narrowest distance in the bony region was (10.96 ± 1.39) mm, (5.41 ± 0.97 mm) in the bone-ligament region. The narrowest distance of bony region in the A1 group was more than that in the A2 group (11.21 ± 1.62 mm, 10.85 ± 1.47 mm, p = 0.029). The narrowest distance of the bony region was (10.21 ± 1.42) mm and (11.65 ± 1.39) mm in the B1 group and B2 group, respectively (p = 0.002). The narrowest distance of the bone-ligament region was (5.39 ± 0.78) mm and (5.22 ± 1.21) mm in the A1 group and A2 group, respectively. No statistically significant differences were observed between the A1 group and the A2 group in terms of the narrowest distance of the bone-ligament region. In the B1 group, the narrowest distance of the bone-ligament region (5.18 ± 0.71 mm) was not significantly less than that (5.31 ± 0.91 mm) in the B2 group. Conclusion The space above the fibular capitellum was ample enough to place the plate for treating tibial plateau fractures involving posterolateral quadrant. The divisions of the lateral tibial plateau by 3-dimensional CT and the parameters of each region were crucial for providing guidance for designing the anatomical plate for the trans-fibular-head approach.

Electrode wear during electrical discharge machining (EDM) is inevitable, and tool electrodes of different materials exhibit different wear rates. Unlike a single-material tool electrode, for a laminated electrode consisting of various material foils (LE-VMF), the components suffer from significantly different amounts of wear and also influence each other in EDM, however, the form and cause of the wear are not clear. Thus, the LE-VMFs including symmetric and asymmetric LE-VMFs were prepared and used in EDM in this paper. The wear of foils in LE-VMFs and their mutual influence during the EDM process were investigated through experiments. The wear forms of a single foil electrode and a foil of the same material in the LE-VMF were also compared. The experimental results show that copper foil with a lower wear rate had a protective effect on an adjacent brass foil with a larger wear rate in the LE-VMF, while the protective effect of the brass foil in the symmetric LE-VMF was larger than that in the asymmetric LE-VMF. The closer the distance from the copper foil, the stronger was the protection effect and the smaller was the wear. In addition, the working surface of the brass foil in the LE-VMF did not show any concavity-like wear in the middle region of its thickness after EDM, as was the case for the single brass foil electrode, even if the thickness of the brass foil was greater than 150 μm.

IntroductionThe administration of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) has been a subject of debate, and its potential benefits remain uncertain. This retrospective study aimed to investigate the effect of preoperative IVT on glycocalyx damage in patients with cerebral ischemia-reperfusion injury (IRI).MethodsA cohort of 106 patients with acute large vessel occlusion in the anterior circulation treated with mechanical thrombectomy was enrolled. The levels of the glycocalyx damage marker, syndecan-1, were measured in the peripheral blood of these patients to assess glycocalyx damage during IRI, and clinical outcomes were compared between patients receiving MT alone vs. combined IVT and MT.ResultsThe study results indicate that thrombolytic drugs have a significant impact on syndecan-1 levels in the blood. Compared to patients who underwent direct MT, those who received preoperative IVT had significantly lower levels of syndecan-1 in their blood. Although preoperative IVT did not alter the final clinical outcomes, the levels of syndecan-1 shedding reflect the extent of damage to the endothelial glycocalyx.DiscussionThis suggests that using thrombolytic drugs before mechanical thrombectomy may reduce endothelial glycocalyx damage in patients with ischemia-reperfusion injury. These findings provide indirect clinical evidence supporting the preoperative use of intravenous thrombolysis in such patients.

The Regional Pest Control program represents a strategic intervention aimed at optimizing pesticide use in crop production, thereby mitigating the environmental impact of agricultural non-point source pollution from pesticides and fostering the development of high-quality agriculture. This study examines the influence of farmers’ perceived risks on the adoption of the Regional Pest Control program and evaluates its effect on pesticide application across a nationally representative dataset from Heilongjiang, Jiangsu, Anhui, Hubei, and Sichuan provinces. To account for unobserved heterogeneity, an endogenous switching regression model was employed. The findings reveal that farmers’ perceived risks associated with the Regional Pest Control program significantly deter its adoption. Furthermore, the program has been effective not only in reducing the frequency of pesticide applications but also in increasing the usage of pesticides with lower acute toxicity levels. Notably, the impact of the Regional Pest Control program on pesticide application demonstrates considerable variation in accordance with farmers’ risk attitudes.

Background: Laparoscopic cholecystectomy (LC) is required for acute cholecystitis patient with percutaneous transhepatic gallbladder drainage (PTGBD). However, it's unknown how to distinguishing the surgical difficulty for these patients. Methods: Data of patients who underwent LC after PTGBD between 2016 and 2022 were collected. Patients were categorized into difficult and non-difficult operations based on operative time, blood loss, and surgical conversion. Performance of prediction model was evaluated by ROC, calibration, and decision curves. Results: A total of 127 patients were analyzed, including 91 in non-difficult operation group and 36 in difficult operation group. Elevated CRP (P = 0.011), pericholecystic effusion (P

ObjectiveThis study explores the intricate relationship between social support and eating behaviors in children and adolescents, considering the mediating role of eating self-efficacy and the moderating effects of body mass index (BMI) and weight concern.MethodsData from 1986 primary and secondary school students aged 8 to 17 in Shanghai, China, were analyzed using moderated mediation analysis.ResultsThe results demonstrate a robust positive association between social support and eating self-efficacy, particularly prominent among individuals with low BMI (effect = 0.506, 95% CI [0.376, 0.636]). Moreover, the study highlights that eating behavior is influenced not only by eating self-control (β = −0.054, 95% CI [−0.062, −0.046]) but also by the interaction term between individuals’ perceptions of their body weight (β = −0.0008, 95% CI [−0.0015, −0.0001]).ConclusionEating self-efficacy serves as a mediator in the relationship between social support and eating behavior, modulated by BMI and weight concern. Importantly, high weight concern significantly strengthens the mediating effect of eating self-efficacy on the relationship between social support and eating behavior, regardless of BMI.

ObjectiveRhizosphere microorganisms play crucial roles in the growth and development of plants, disease resistance, and environmental adaptability. As the only wild pepper variety resource in China, domesticated Capsicum frutescens Linn. (Xiaomila) exhibits varying beneficial traits and affects rhizosphere microbial composition compared with its wild counterparts. In this study, we aimed to identify specific rhizosphere microbiome and metabolism patterns established during the domestication process.MethodsThe rhizosphere microbial diversity and composition of domesticated and wild C. frutescens were detected and analyzed by metagenomics. Non-targeted metabolomics were used to explore the differences of metabolites in rhizosphere soil between wild and domesticated C. frutescens.ResultsWe found that the rhizosphere microbial diversity of domesticated variety was significantly different from that of the wild variety, with Massilia being its dominant bacteria. However, the abundance of certain beneficial microbes such as Gemmatimonas, Streptomyces, Rambibacter, and Lysobacter decreased significantly. The main metabolites identified in the wild variety included serylthreonine, deoxyloganic acid, vitamin C, among others. In contrast, those identified in the domesticated group were 4-hydroxy-l-glutamic acid and benzoic acid. Furthermore, the differentially enriched pathways were concentrated in tyrosine and tryptophan biosynthesis, histidine and purine-derived alkaloids biosynthesis, benzoic acid family, two-component system, etc.ConclusionThis study revealed that C. frutescens established specific rhizosphere microbiota and metabolites during domestication, which has important significance for the efficient utilization of beneficial microorganisms in breeding and cultivation practices.

In the context of accelerating ecological fragmentation, it is urgent to enhance the interconnectivity of urban ecological patches to form a resilient ecological network (EN). The construction of a Natural Protected Area (NPA) system proposed in 2019 is the latest strategy implemented by China in protecting ecological spaces. However, the effectiveness of this strategy has not been adequately demonstrated. This study specifically analyzes the concrete impacts of the natural protected area system on the resilience of ecological networks (ENs). The economically developed Urban Agglomeration around Hangzhou Bay (UAHB) was chosen as an example for the argumentation. Firstly, we utilized circuit theory to construct an EN consisting of 173 ecological sources and 401 ecological corridors. Secondly, the ecological sources were categorized into three levels based on their connectivity values. Finally, a dynamic disturbance scenario simulation framework was constructed to evaluate the impact of NPA on the resilience of EN. The results indicated that: (1) The preceding 47% of ecological sources are crucial for maintaining the resilience of the EN; (2) Compared with other ecological spaces, NPAs have a 38% and 1100% greater effect on the resilience of the EN in first and second-level ecological sources, respectively, while its impact in third-level is 118% lower. This study innovatively investigates the differential impacts of hierarchical natural protected areas and natural unprotected areas on the ecological environment.

Abstract Aggregation‐induced emission (AIE) is an intriguing photophysical phenomenon, where specific materials exhibit a remarkable surge in luminescence when brought together in non‐ideal solvents or within a solid matrix. Since the concept of AIE was first introduced in 2001, numerous advanced applications have been gradually explored across various domains, including optics, electronics, energy, and the life sciences. Of particular note is the growing interest in the application of AIE systems with near‐infrared (NIR) emissive feature in the field of biomedicine, encompassing detection, imaging, and therapeutic interventions. Notably, bibliometric analysis serves as a valuable tool to provide researchers with a comprehensive understanding of research achievements and developmental trends in specific fields, which is crucial for academic research. Herein, we present a general bibliometric overview spanning two decades of NIR‐AIE development. With the assistance of core scientific databases and various bibliometric software tools, we conducted a systematic analysis of annual publications and citations, the most influential countries/regions, leading authors, journals, and institutions, as well as the hot topics related to NIR applications and forward‐looking predictions. Furthermore, the application of AIE with NIR properties in the biomedical field is also systematically reviewed.

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents’ safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents.

Focusing on the plasma wakes of hypersonic targets (PWHT), this work provides a method for the inversion of electron densities in the PWHT by integrating electromagnetic radiation theory and three-wave coupling theory (TWCT). Utilizing the Computational Fluid Dynamics (CFD) method, taking a blunt cone as an example, the spatial distribution characteristics of electron densities in the plasma wake are simulated and analyzed in detail. The Zakharov system of equations (ZSE) is applied to the PWHT for the discussion about the electromagnetic radiation generated by plasma parametric instability. Combining the wavenumber spectrum of electromagnetic radiation and the TWCT, an inverse method of the electron densities of plasma wakes is proposed and applied to a blunt cone model. The results indicate that the inversion error rate is effectively held below 1.37 %. Furthermore, reasons for errors are elucidated through the utilization of the wavenumber spectrum structure. The proposed method may contribute to the development of hypersonic wake diagnostic techniques, and offer new insights and directions for wind tunnel experiments, shock tube experiments, as well as research on hypersonic target detection.

Due to the high heterogeneity of ovarian cancer (OC), it occupies the main cause of cancer-related death among women. As the most aggressive and frequent subtype of OC, high-grade serous cancer (HGSC) represents around 70 % of all patients. With the booming progress of single-cell RNA sequencing (scRNA-seq), unique and subtle changes among different cell states have been identified including novel risk genes and pathways. Here, our present study aims to identify differentially correlated core genes between normal and tumor status through HGSC scRNA-seq data analysis. R package high-dimension Weighted Gene Co-expression Network Analysis (hdWGCNA) was implemented for building gene interaction networks based on HGSC scRNA-seq data. DiffCorr was integrated for identifying differentially correlated genes between tumor and their adjacent normal counterparts. Software Cytoscape was implemented for constructing and visualizing biological networks. Real-time qPCR (RT-qPCR) was utilized to confirm expression pattern of new genes. We introduced ScHGSC-IGDC (Identifying Genes with Differential Correlations of HGSC based on scRNA-seq analysis), an in silico framework for identifying core genes in the development of HGSC. We detected thirty-four modules in the network. Scores of new genes with opposite correlations with others such as NDUFS5, TMSB4X, SERPINE2 and ITPR2 were identified. Further survival and literature validation emphasized their great values in the HGSC management. Meanwhile, RT-qPCR verified expression pattern of NDUFS5, TMSB4X, SERPINE2 and ITPR2 in human OC cell lines and tissues. Our research offered novel perspectives on the gene modulatory mechanisms from single cell resolution, guiding network based algorithms in cancer etiology field.

Abstract Understanding the impact of long‐term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency. However, this has been limited by human brain inaccessibility and cross‐species differences in animal models. Here, a human midbrain model is established that uses hiPSC‐derived midbrain organoids to assess cell‐type‐specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single‐cell mRNA sequencing of 25,510 cells from organoids in different treatment groups reveals that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single‐cell level.

The severe erosion and inadequate mechanical strength are prominent challenges for high-energy gun propellants. To address it, novel PTW@PDA composites was prepared by polydopamine(PDA)-modifying onto potassium titanate whisker(PTW, K2Ti6O13), and after was incorporated into gun propellant as erosion-reducing and mechanical-reinforcing fillers. The interfacial characterizations results indicated that as-prepared PTW@PDA composites exhibits an enhanced surface compatible with propellant matrix, thereby facilitating their dispersion into propellants more effectively than raw PTW materials. Compared to original propellants, PTW@PDA-modified propellants exhibited significant less erosion, with a Ti–K-based protective coating being detected on the eroded steel. And 0.5 wt% and 1.0 wt% addition of PTW@PDA significantly improved impact, compressive and tensile strength of propellants. Despite the inevitably reduction in relative force, PTW@PDA slightly increase propellant burning rate while exerting little adverse impact on propellant dynamic activity. This strategy can provide a promising alternative to develop high-energy gun propellant with less erosion and more mechanical strength.

In recent years, S-(alkyl)thianthrenium salts have become an important means of functionalizing alcohol compounds. However, additional transition metal catalysts and/or visible light are required. Herein, a direct thioetherification/amination reaction of thianthrenium salts is realized under metal-free conditions. This strategy exhibits good functional-group tolerance, operational simplicity, and an extensive range of compatible substrates.

Abstract This thesis proposes a charging equalizer for hybrid energy storage systems, incorporating the Zeta converter, voltage multiplier, and multi‐winding transformer. The objective is efficient charging and equalization for battery and supercapacitor strings. The Zeta converter serves to charge the battery string, while the transformer with multi‐winding shares the inductor of Zeta converter as the primary side, facilitating battery string balancing through the utilization of current ripple in the inductor. Additionally, the voltage ripple generated by the Zeta converter is utilized to drive the voltage multiplier, enabling the charging and equalization of the supercapacitor string. The system's operation halts upon reaching the predefined threshold voltage for the supercapacitor strings. The proposed circuit transforms into a Zeta converter by employing a single‐pole double‐throw switch, facilitating the charging of the battery strings. Experimental validation uses four series‐connected supercapacitors and four series‐connected batteries, demonstrating successful equalization and charging for both energy storage components.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.

In this paper, a novel adaptive neural fault-tolerant control scheme is proposed for uncertain large nonlinear systems with sensor, actuator faults and dead zone. Due to the fault of the sensor, the actual state and the fault parameters are coupled, and a fault parameter separation method is designed for decoupling. The radial basis function neural network (RBFNN) is used to approximate the unknown interconnection functions in nonlinear systems, and combining the RBFNN and backstepping technology, an adaptive neural fault-tolerant controller is designed for nonlinear large-scale systems through ordinary Lyapunov function. The stability of the closed-loop system is verified by Lyapunov analysis, and obtained satisfactory tracking performance under the comprehensive influence of sensor, actuator faults and dead zone. Finally, the effectiveness of the proposed adaptive neural fault-tolerant control is illustrated by simulation of large-scale wind farm system.

Abstract Information technology has brought about significant changes in enterprises, and new work situations have led to new problems. Employee resistance to new technologies, their ability to learn, and their ability to utilize personal resources to improve work engagement in the face of technological pressure are important factors that companies need to consider when undergoing digital transformation. The influence mechanism of configuration effects on factors around employee work engagement has not been explored, and technostress creators have rarely been included in the configuration as influencing factors in previous studies. On the basis of the job demands-resources (JD-R) model and trait activation theory, this study explored the factors that affect employees’ work engagement at the level of job demands and personal resources. The fuzzy-set qualitative comparative analysis (fsQCA) method was used to investigate the influence of technical stressors, self-efficacy, and the Big Five personality traits on employees’ work engagement. Through a survey of 225 employees in the context of enterprise digital transformation, the results show three driving paths that promote employees’ work engagement: openness to experience conscientiousness, self-efficacy driven, and inhibition to technical stressors. The study also analyzed employees’ low work engagement state, which is driven by an inhibition of agreeableness and extraversion. This research enriches the study of factors influencing work engagement in the digital transformation of enterprises.