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Abstract The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and immune/neurological disorders. Here, we apply native mass spectrometry (MS)-based approaches to provide evidence of super-dimer formation (LAT1-4F2hc)2. When combined with lipidomics, and site-directed mutagenesis, we discover four endogenous phosphatidylethanolamine (PE) molecules at the interface and C-terminus of both LAT1 subunits. We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP), we reveal that super-dimerization is sensitive to pH, and modulated by complex N-glycans on the 4F2hc subunit. We further validate the dynamic assemblies of LAT1-4F2hc on plasma membrane and in the lysosome. Together our results link PTM and lipid binding with regulation and localisation of the LAT1-4F2hc super-dimer.

Abstract Background This study aimed to investigate the impact of self-consciousness on depression of college students, and mainly focus on confirming the mediator role of life meaningful and self-efficacy, as well as the moderator role of social support. Methods In the present study, convenient sampling method was adopted, 583 college students were recruited from Harbin city and Wenzhou city in China. All students were assessed using self-assessment scales, including self-consciousness scale, life meaningful scale, self-efficacy scale, social support scale, and self-rating depression scale. Descriptive statistical analysis and correlation analysis, structural equation model analysis were conducted by SPSS 25.0 and M-plus. Results Results showed that self-consciousness was negatively related to depression, life meaningful and self-efficacy partially mediated the relation between self-consciousness and depression. Moderated mediation analysis further indicated that the relation between self-efficacy and depression were moderated bu social support. Compare with college students who had high social support, depression in those with low social support was more susceptible to the effect of self-efficacy. Conclusion These findings imply that college students with low levels of self-consciousness are more easy to be depressive, enhancing their sense of life meaning and self-efficacy can effectively alleviate depression, and college student with high social support can benefit more from self-efficacy. Therefore we should pay more attention to the mental health problems of low levels self-consciousness college students in university.

Abstract Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a tumor growth-promoting phenotype through activation of the anaplastic lymphoma kinase (ALK) signaling pathway. Targeting the RNase1/ALK axis reprograms the macrophage polarization, with increased CD8+ T- and Th1- cell recruitment. Moreover, simultaneous targeting of the checkpoint protein PD-1 unleashes cytotoxic CD8+ T-cell responses. Treatment utilizing both an ALK inhibitor and an anti-PD-1 antibody exhibits enhanced tumor regression and facilitates long-term immunity. Our study elucidates the role of RNase1 in mediating tumor resistance to immunotherapy and reveals an RNase1-mediated immunosuppressive tumor microenvironment, highlighting the potential of targeting RNase1 as a promising strategy for cancer immunotherapy in HCC.

Abstract To advance the full potential of quantum networks one should be able to distribute quantum resources over long distances at appreciable rates. As a consequence, all components in such networks need to have large multimode capacity to manipulate photonic quantum states. Towards this end, a photonic quantum memory with a large multimode capacity, especially one operating at telecom wavelength, remains an important challenge. Here we optimize the preparation of atomic frequency combs and demonstrate a spectro-temporally multiplexed quantum memory in a 10-m-long cryogenically cooled erbium doped silica fibre. Our multiplexing storage has five spectral channels - each 10 GHz wide with 5 GHz separation - with up to 330 temporal modes in each, thus resulting in a simultaneous storage of 1,650 modes of heralded single photons with a 1000-fold increasing in coincidence detection rate with respect to single mode storage. Our results could pave the way for high speed quantum networks compatible with the infrastructure of fibre optical communication.

By considering the joint effects of the Kelvin–Helmholtz (KH) and Rayleigh–Taylor (RT) instabilities, this paper presents an interpretation of the wavy patterns that occur in explosive welding. It is assumed that the elasticity of the material at the interface effectively determines the wavelength, because explosive welding is basically a solid-state welding process. To this end, an analytical model of elastic hydrodynamic instabilities is proposed, and the most unstable mode is selected in the solid phase. Similar approaches have been widely used to study the interfacial behavior of solid metals in high-energy-density physics. By comparing the experimental and theoretical results, it is concluded that thermal softening, which significantly reduces the shear modulus, is necessary and sufficient for successful welding. The thermal softening is verified by theoretical analysis of the increase in temperature due to the impacting and sliding of the flyer and base plates, and some experimental observations are qualitatively validated. In summary, the combined effect of the KH and RT instabilities in solids determines the wavy morphology, and our theoretical results are in good qualitative agreement with experimental and numerical observations.

Taking CL-20 (Hexanitrohexaazaisowurtzitane)-based aluminized explosives with high gurney energy as the research object, this research experimentally investigates the work capability of different aluminized explosive formulations when driving metal flyer plates in the denotation wave propagation direction. The research results showed that the formulations with 43 μm aluminum (Al) powder particles (The particle sizes of Al powder were in the range of 2∼43 μm) exhibited the optimal performance in driving flyer plates along the denotation wave propagation direction. Compared to the formulations with Al powder 13 μm, the formulations with Al powder 2 μm delivered better performance in accelerating metal flyer plates in the early stage, which, however, turned to be poor in the later stage. The CL-20-based explosives containing 25% Al far under-performed those containing 15% Al. Based on the proposed quasi-isentropic hypothesis, relevant isentropy theories, and the functional relationship between detonation parameters and entropy as well as Al reaction degree, the characteristic lines of aluminized explosives in accelerating flyer plates were theoretically studied, a quasi-isentropic theoretical model for the aluminized explosive driving the flyer plate was built and the calculation methods for the variations of flyer plate velocity, Al reaction degree, and detonation product parameters with time and axial positions were developed. The theoretical model built is verified by the experimental results of the CL-20-based aluminized explosive driving flyer plate. It was found that the model built could accurately calculate the variations of flyer plate velocity and Al reaction degree over time. In addition, how physical parameters including detonation product pressure and temperature varied with time and axial positions was identified. The action time of the positive pressure after the detonation of aluminized explosives was found prolonged and the downtrend of the temperature was slowed down and even reversed to a slight rise due to the aftereffect reaction between the Al powder and the detonation products.

As the protective component, steel plate had attracted extensive attention because of frequently threats of explosive loads. In this paper, the evolution of microstructure and the mechanism of damage in the quasi-cracking area of steel plate subjected to explosive load were discussed and the relationships between micro defects and dynamic mechanical response were revealed. After the explosion experiment, five observation points were selected equidistant from the quasi-cracking area of the section of the steel plate along the thickness direction, and the characteristics of micro defects at the observation points were analyzed by optical microscope (OM), scanning electron microscope (SEM) and electron back-scattered diffraction (EBSD). The observation result shows that many slip bands (SBs) appeared, and the grain orientation changed obviously in the steel plate, the two were the main damage types of micro defects. In addition, cracks, peeling pits, grooves and other lager micro defects were appeared in the lower area of the plate. The stress parameters of the observation points were obtained through an effective numerical model. The mechanism of damage generation and crack propagation in the quasi-cracking area were clarified by comparing the specific impulse of each observation point with the corresponding micro defects. The result shows that the generation and expansion of micro defects are related to the stress area (i.e. the upper compression area, the neutral plane area, and the lower tension area). The micro defects gather and expand at the grain boundary, and will become macroscopic damage under the continuous action of tensile stress. Besides, the micro defects at the midpoint of the section of the steel plate in the direction away from the explosion center (i.e. the horizontal direction) were also studied. It was found that the specific impulse at these positions were much smaller than that in the thickness direction, the micro defects were only SBs and a few micro cracks, and the those decreased with the increase of the distance from the explosion center.

AbstractThe genus Sinosenecio B. Nordenstam is a group of perennial or sometimes annual or biennial herbs in the family Asteraceae. Here, we have successfully assembled and characterized the complete chloroplast (cp) genome of S. globigerus, which shows a typical quadratic structure with an overall GC content of 37.4%, comprising a pair of inverted repeat regions (IRs) of 24,848 bp, a large single-copy region (LSC) of 83,379 bp and a small single-copy region (SSC) of 18,180 bp. 133 genes were annotated, including 88 protein-coding genes, 37 tRNA genes and eight rRNA genes. Further nucleotide diversity analysis indicated that three genomic regions (accD-psaI, trnK-rps16, and ycf1) exhibited sufficient variability and thus could be recommended as valuable barcodes for the delimitation and identification of Sinosenecio species. Phylogenetic reconstruction presented clear interspecific relationships within Sinosenecio, which were supported to some extent by cytology, morphology and geographic distributions. Our study will provide valuable and high-quality genetic information to further elucidate the diversified mechanisms in Sinosenecio.

Grain weight is one of the key components of wheat (Triticum aestivum L.) yield. Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs. A recombinant inbred line (RIL) population derived from a cross between W7268 and Chuanyu 12 (CY12) was employed to detect quantitative trait loci (QTLs) for thousand-grain weight (TGW), grain length (GL), grain width (GW), and the ratio of grain length to width (GLW) in six environments. Seven major QTLs, QGl.cib-2D, QGw.cib-2D, QGw.cib-3B, QGw.cib-4B.1, QGlw.cib-2D.1, QTgw.cib-2D.1 and QTgw.cib-3B.1, were consistently identified in at least four environments and the best linear unbiased estimation (BLUE) datasets, and they explained 2.61 to 34.85% of the phenotypic variance. Significant interactions were detected between the two major TGW QTLs and three major GW loci. In addition, QTgw.cib-3B.1 and QGw.cib-3B were co-located, and the improved TGW at this locus was contributed by GW. Unlike other loci, QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike (GNS). They were further validated in advanced lines using Kompetitive Allele Specific PCR (KASP) markers, and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus. Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars. According to gene annotation, spatial expression patterns, ortholog analysis and sequence variation, the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted. Collectively, the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.

Steel-like density HfZrTiTa0.2Al0.8 high entropy alloy (HEA) with a density of 7.78 g/cm3 is designed and fabricated as a novel energetic structural material (ESM). The microstructure, thermal analysis, compressive mechanical properties, ignition and energy release under dynamic loading are systemically investigated. The experimental results show that the HfZrTiTa0.2Al0.8 HEA has a single BCC solid solution structure, and spinodal decomposition with elements segregation in the nanoscale is observed. Thermal analysis shows the HEA keeps stable in the Ar atmosphere and the oxidizing reaction occurs in the Air atmosphere. The mechanical properties show brittle characteristics with maximum strength with 1520 MPa and fracture strain 0.07 and strain rate effect from 0.001s−1 to 3000s−1 is observed. Under high strain rate loading, the fracture-induced spark is observed, which is caused by an oxidizing reaction due to the rise. By direct ballistic test, the energy release velocity threshold is measured as 980 m/s, and the energy release intensity is more violent in higher velocity impact conditions. Moreover, the impact reaction degree is increased with increasing fragmentation degree and adiabatic temperature rise induced by impact. The designed HEA-ESM is a promising candidate that simultaneously possesses both high strength, high reactive heat and excellent energetic characteristics in the application field of high-strength ESM fragment.

Copper/stainless steel composite is often used for preparation of superconducting busbar “double box” lap joints. However, it is a challenge for the large thickness T2 copper/316L stainless steel composite is fabricated by explosive welding, because of the bonding interface is always present many problems such as large ripple size, many microscopic defects, low bonding strength and poor sealing etc. In this paper, the big-thickness T2 copper/316L stainless steel composite with small size wavy interface was successfully fabricated by explosive welding. Microstructure of bonding interface indicated that the welding process could be divided into three stages: detonation growth stage, detonation stabilization stage, detonation descent stage. The morphology of bonding interface presented a regular wavy interface and no defects such as cracks, voids and intermetallic compound were formed in the stable stage, which was consistent with the results of ultrasonic and permeability quality inspection. The hardness of copper side and stainless steel side close to the bonding interface reached 131HV and 432HV, respectively. Dynamic recrystallization and fine grain generated in the bonding interface. The mechanical properties of tensile strength, pull-off strength and shear strength in the stable detonation stage is greater than 110 MPa, which is meeting the requirements of preparation of superconducting busbar “double box” lap joints. The deformation failure mainly occurred in the copper side near the bonding interface, which presented a higher bonding strength than copper. Some dimples and tearing edges with different sizes on the fracture surfaces, indicating that the fracture was a typical ductile fracture.

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases. CD36 was recently found to be widely expressed in various cell types in the nervous system, including endothelial cells, pericytes, astrocytes, and microglia. CD36 mediates a number of regulatory processes, such as endothelial dysfunction, oxidative stress, mitochondrial dysfunction, and inflammatory responses, which are involved in many central nervous system diseases, such as stroke, Alzheimer’s disease, Parkinson’s disease, and spinal cord injury. CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand, thereby achieving inhibition of CD36-mediated pathways or functions. Here, we reviewed the mechanisms of action of CD36 antagonists, such as Salvianolic acid B, tanshinone IIA, curcumin, sulfosuccinimidyl oleate, antioxidants, and small-molecule compounds. Moreover, we predicted the structures of binding sites between CD36 and antagonists. These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

Abstract Prostate cancer (PCa) is a significant health concern affecting men worldwide. Previous studies have shown that nimotuzumab, a drug targeting the epidermal growth factor receptor (EGFR), can effectively inhibit cancer progression. Here, we aimed to explore the role of miR‐199a/214 cluster in mediating the inhibitory effect of nimotuzumab on the development of PCa. In this study, we conducted an MTT assay to assess cell proliferation and utilized flow cytometry to evaluate cell apoptosis and cell cycle arrest. To investigate the molecular mechanisms underlying the effects of nimotuzumab on prostate cancer development, we focused on the miR‐199a‐5p and miR‐214‐3p miRNA clusters. The TargetScan Human database was used to predict the binding sites between miR‐199a‐5p or miR‐214‐3p and the 3'‐UTR of the transducin (β)‐like 1 X‐linked receptor 1 (TBL1XR1) mRNA. To confirm the direct interaction and binding between miR‐199a‐5p or miR‐214‐3p and the 3'‐UTR of TBL1XR1 mRNA, we performed luciferase reporter assays. Our findings demonstrated that nimotuzumab exerted a significant dosage‐dependent suppression of PCa cell proliferation and facilitated PCa cell apoptosis and cell cycle arrest. Concurrently, nimotuzumab obviously impeded the activity of Wnt/β‐catenin and EGFR signaling pathways in PCa cells. We also observed downregulation of miR‐199a‐5p and miR‐214‐3p in PCa cells. Overexpression of miR‐199a/214 cluster inhibited PCa cell viability and enhanced cell apoptosis. Furthermore, we found that miR‐199a/214 cluster augmented the inhibitory effect of nimotuzumab on PCa cell proliferation and promoted its ability to induce apoptosis and cell cycle arrest. This effect was reversed upon TBL1XR1 overexpression, indicating that TBL1XR1 is involved in the regulatory pathway of miR‐199a/214 and nimotuzumab in PCa cells. We further revealed that TBL1XR1 was overexpressed in PCa and was identified as a downstream target of the miR‐199a/214 cluster. In nimotuzumab‐treated PCa cells, the overexpression of miR‐199a/214 markedly inhibited Wnt/β‐catenin and EGFR signaling, and this effect was also rescued by TBL1XR1 overexpression. In summary, our data indicated that miR‐199a/214 cluster play a crucial role in enhancing the inhibitory effect of nimotuzumab on PCa development by downregulating TBL1XR1 and modulating Wnt/β‐catenin and EGFR signaling pathways. These findings offer a novel therapeutic approach for the treatment of prostate cancer.

Developing efficient electrocatalysts for converting dinitrogen to ammonia through electrocatalysis is of significance to the decentralized ammonia production. Here, through high-throughput density functional theory calculations, we demonstrated that the interfacial modulation of hexagonal boron nitride/graphene (hBN-graphene) could sufficiently improve the catalytic activity of the single transition metal atom catalysts for nitrogen reduction reaction (NRR). It was revealed that Re@hBN-graphene and Os@hBN-graphene possessed remarkable NRR catalytic activity with low limiting potentials of 0.29 V and 0.33 V, respectively. Furthermore, the mechanism of the enhanced catalytic activity was investigated based on various descriptors of the adsorption energies of intermediates, where the synergistic effect of hBN and graphene in the hybrid substrate was found to play a key role. Motivated by the synergistic effect of hybrid substrate in single-atom catalysts, a novel strategy was proposed to efficiently design dual-atom catalysts by integrating the merits of both metal components. The as-designed dual-atom catalyst Fe-Mo@hBN exhibited more excellent NRR catalytic performance with a limiting potential of 0.17 V, manifesting the solidity of the design strategy. Our findings open new avenues for the search of heterostructure substrates for single-atom catalysts and the efficient design of dual-atom catalysts for NRR.

Abstract Aspirin, also named acetylsalicylate, can directly acetylate the side‐chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic‐labeling aspirin‐d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+‐dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity. Interestingly, the lysine 408 of SIRT1 can be acetylated by CBP acetyltransferase in cells without aspirin supplement. Aspirin can inhibit SIRT1 to increase the levels of acetylated p53 and promote p53‐dependent apoptosis. Moreover, the knock‐in mice of the acetylation‐mimic mutant of SIRT1 show the decreased production of pro‐inflammatory cytokines and maintain intestinal immune homeostasis. The study indicates the importance of the acetylated internal functional site of SIRT1 in maintaining intestinal immune homeostasis.

[Abstract]: Objective: This study aimed to investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) and any possible interactions between specific MTHFR alleles and traditional risk factors among a Han Chinese cohort. Methods: 434 AIS patients were consecutively recruited between January 2017 and June 2019, including 129 END and 305 non-END cases. A candidate gene association study design was used to analyze the association between MTHFR gene polymorphism and END risk. The polymerase chain reaction-restriction fragment length polymorphism (RFLP) method was employed to genotype the MTHFR C677T polymorphism. The interactional analyses were performed using the multifactor dimensionality reduction test. Results: Hyperglycemia (odds ratio [OR]: 2.410, 95 % confidence interval [CI]: 1.436–4.046, p = 0.001), neurological function impairment (NIHSS score >5) (OR: 2.158, 95%CI: 1.337–3.484, p = 0.002) on admission, and hyperhomocysteinemia (HHcy) (OR: 2.570, 95%CI: 1.229–5.376, p = 0.012) were independently associated with END. The TT genotype (OR: 1.710, 95%CI: 1.021–2.863, p = 0.043) and T allele (OR: 1.710, 95%CI: 1.021–2.863, p = 0.043) of this C677T polymorphism were associated with susceptibility to END, and the TT genotype was more common in the subjects with HHcy (OR: 2.525, 95%CI: 1.111–5.739, P = 0.023). In addition, we also found interactions for END risk between the C677T polymorphism and traditional risk factors for END, including: hyperglycemia on admission, drinking, and moderate to severe neurological deficits (OR 1.237, 95 % CI 0.227–6.734), although the results were not statistically significant (p = 0.806). Conclusions: Our results show a possible association between MTHFR C677T polymorphism and gene–environment interactions with END susceptibility in a Han Chinese cohort.

BackgroundWhile increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population.ObjectiveThis study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults.MethodsIn our study, we evaluated 8,135 individuals aged 18–59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia.ResultsAfter adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 μg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups.ConclusionOur results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 μg/L.

BackgroundThere is a dearth of feasibility assessments regarding using large language models (LLMs) for responding to inquiries from autistic patients within a Chinese-language context. Despite Chinese being one of the most widely spoken languages globally, the predominant research focus on applying these models in the medical field has been on English-speaking populations. ObjectiveThis study aims to assess the effectiveness of LLM chatbots, specifically ChatGPT-4 (OpenAI) and ERNIE Bot (version 2.2.3; Baidu, Inc), one of the most advanced LLMs in China, in addressing inquiries from autistic individuals in a Chinese setting. MethodsFor this study, we gathered data from DXY—a widely acknowledged, web-based, medical consultation platform in China with a user base of over 100 million individuals. A total of 100 patient consultation samples were rigorously selected from January 2018 to August 2023, amounting to 239 questions extracted from publicly available autism-related documents on the platform. To maintain objectivity, both the original questions and responses were anonymized and randomized. An evaluation team of 3 chief physicians assessed the responses across 4 dimensions: relevance, accuracy, usefulness, and empathy. The team completed 717 evaluations. The team initially identified the best response and then used a Likert scale with 5 response categories to gauge the responses, each representing a distinct level of quality. Finally, we compared the responses collected from different sources. ResultsAmong the 717 evaluations conducted, 46.86% (95% CI 43.21%-50.51%) of assessors displayed varying preferences for responses from physicians, with 34.87% (95% CI 31.38%-38.36%) of assessors favoring ChatGPT and 18.27% (95% CI 15.44%-21.10%) of assessors favoring ERNIE Bot. The average relevance scores for physicians, ChatGPT, and ERNIE Bot were 3.75 (95% CI 3.69-3.82), 3.69 (95% CI 3.63-3.74), and 3.41 (95% CI 3.35-3.46), respectively. Physicians (3.66, 95% CI 3.60-3.73) and ChatGPT (3.73, 95% CI 3.69-3.77) demonstrated higher accuracy ratings compared to ERNIE Bot (3.52, 95% CI 3.47-3.57). In terms of usefulness scores, physicians (3.54, 95% CI 3.47-3.62) received higher ratings than ChatGPT (3.40, 95% CI 3.34-3.47) and ERNIE Bot (3.05, 95% CI 2.99-3.12). Finally, concerning the empathy dimension, ChatGPT (3.64, 95% CI 3.57-3.71) outperformed physicians (3.13, 95% CI 3.04-3.21) and ERNIE Bot (3.11, 95% CI 3.04-3.18). ConclusionsIn this cross-sectional study, physicians’ responses exhibited superiority in the present Chinese-language context. Nonetheless, LLMs can provide valuable medical guidance to autistic patients and may even surpass physicians in demonstrating empathy. However, it is crucial to acknowledge that further optimization and research are imperative prerequisites before the effective integration of LLMs in clinical settings across diverse linguistic environments can be realized. Trial RegistrationChinese Clinical Trial Registry ChiCTR2300074655; https://www.chictr.org.cn/bin/project/edit?pid=199432

Accurately predicting the production rate and estimated ultimate recovery (EUR) of shale oil wells is vital for efficient shale oil development. Although numerical simulations provide accurate predictions, their high time, data, and labor demands call for a swifter, yet precise, method. This study introduces the Duong–CNN–LSTM (D-C-L) model, which integrates a convolutional neural network (CNN) with a long short-term memory (LSTM) network and is grounded on the empirical Duong model for physical constraints. Compared to traditional approaches, the D-C-L model demonstrates superior precision, efficiency, and cost-effectiveness in predicting shale oil production.

BackgroundA growing body of evidence suggests that immunological processes have a significant role in developing idiopathic sudden sensorineural hearing loss (SSHL). However, few studies have examined the association between immune cell phenotype and SSHL using Mendelian Randomization (MR).MethodsThe online genome-wide association studies (GWAS) database was used to compile data from GWAS covering 731 immunophenotypes and SSHL. Inverse variance weighted (IVW) analysis was primarily used for MR study, and single nucleotide polymorphisms (SNPs) associated with immunophenotypes served as dependent variables. A sensitivity study and the false discovery rate (FDR) correction were used to examine the MR hypothesis. In addition, the possibility of reverse causality between immunophenotype and SSHL was validated by reverse MR. Reverse MR was analyzed in a manner consistent with forward MR.ResultsAfter FDR correction and sensitivity analysis, we screened 7 immunophenotypes, including IgD+ CD38dim %lymphocyte (95% CI: 1.0019, 1.0742, p = 3.87 × 10−2, FDR = 1.15 × 10−2); Unsw mem AC (95% CI: 1.004, 1.2522, p = 4.23 × 10−2, FDR = 2.25 × 10−2); CD86+ myeloid DC AC (95% CI: 1.0083, 1.1147, p = 2.24 × 10−2, FDR = 4.27 × 10−2); CD33dim HLA DR− AC (95% CI: 1.0046, 1.0583, p = 2.12 × 10−2, FDR = 4.69 × 10−2); SSC-A on CD8br (95% CI: 1.0028, 1.1461, p = 4.12 × 10−2, FDR = 4.71 × 10−2); CD45RA− CD4+ %T cell (95% CI: 1.0036, 1.0503, p = 2.32 × 10−2, FDR = 4.82 × 10−2); DP (CD4+CD8+) AC (95% CI: 1.011, 1.2091, p = 2.78 × 10−2, FDR = 4.97 × 10−2). There was a strong causal relationship with SSHL onset, and the reliability of the results was verified. Furthermore, the immunological cell profile and SSHL did not appear to be closely associated, as shown by reverse MR analysis.ConclusionOur study provides more support for the current hypothesis that immunophenotypes and the pathophysiology of SSHL are closely associated. Further validation is needed to assess the role of these immunophenotypes in SSHL.

Abstract Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first‐line treatments for IBD have limited efficacy and significant side effects. An innovative H2S‐releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO‐1, PI3K‐AKT, and RAS/MAPK/AP‐1, and inhibiting the p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.

Abstract Developing efficient metal‐nitrogen‐carbon (M‐N‐C) single‐atom catalysts for oxygen reduction reaction (ORR) is significant for the widespread implementation of Zn‐air batteries, while the synergic design of the matrix microstructure and coordination environment of metal centers remains challenges. Herein, a novel salt effect‐induced strategy is proposed to engineer N and P coordinated atomically dispersed Fe atoms with extra‐axial Cl on interlinked porous carbon nanosheets, achieving a superior single‐atom Fe catalyst (denoted as Fe‐NP‐Cl‐C) for ORR and Zn‐air batteries. The hierarchical porous nanosheet architecture can provide rapid mass/electron transfer channels and facilitate the exposure of active sites. Experiments and density functional theory (DFT) calculations reveal the distinctive Fe‐N2P2‐Cl active sites afford significantly reduced energy barriers and promoted reaction kinetics for ORR. Consequently, the Fe‐NP‐Cl‐C catalyst exhibits distinguished ORR performance with a half‐wave potential (E1/2) of 0.92 V and excellent stability. Remarkably, the assembled Zn‐air battery based on Fe‐NP‐Cl‐C delivers an extremely high peak power density of 260 mW cm−2 and a large specific capacity of 812 mA h g−1, outperforming the commercial Pt/C and most reported congeneric catalysts. This study offers a new perspective on structural optimization and coordination engineering of single‐atom catalysts for efficient oxygen electrocatalysis and energy conversion devices.

It is of great significance to prepare liners with excellent inhibition of energetic plasticizer migration and gas barrier properties. Here, we have successfully prepared magnetic iron oxide decorated reduced-graphene-oxide nanosheets (MRGO) by using ultrasound-assisted method. The obtained MRGO nanosheet-fillers were filled into hydroxyl-terminated polybutadiene (HTPB) which was exposed to a magnetic field (200 mT) to achieve ordered orientation of MRGO in the HTPB matrix (Ordered MRGO/HTPB). The laser confocal microscopy demonstrates that MRGO exhibit ordered orientation structure in HTPB matrix with good dispersion, which renders the HTPB composite liners exhibiting high gas and plasticizer barrier capability, with a reduction of 18.9 % in water vapor permeability and a decrease of 14.1 % in dibutyl phthalate (DBP) migration equilibrium concentration as compared with those of random MRGO embedded HTPB composite liners (Random MRGO/HTPB). Moreover, a theoretical model accounting for such enhanced gas/plasticizer barrier performance of HTPB due to the implantation of order aligned MRGO was established, which shows that the effective diffusion pathways of plasticizer/gas for liner penetration would be significantly enhanced when the MRGO nanosheets are oriented within the HTPB matrix. This work provides an effective and facile strategy toward the design and development of composite liners with high plasticizer/gas barrier performance for industrial applications.

Large-depth and multiscale gradient microstructure in dual-phase Al0.6CoCrFeNi high entropy alloy (HEA) were fabricated by explosion hardening (EH) technique. The gradient microstructure evolution was investigated in detail. The microhardness distribution and tensile properties near EH affected surface were also determined. The formation and strengthening mechanisms of gradient microstructure after EH treatment were subsequently analyzed. Experimental results showed that the multiscale gradient microstructure in terms of grain size, phase morphology, dislocation structure, texture was induced in dual-phase (BCC + FCC) HEA by EH technique. The closer to EH affected surface, the finer grain size, higher dislocation density and stronger texture intensity. The deformation and break of spinodal decomposition and formation of new grain boundaries by dislocation structure contributed to grain refinement and transition of equiaxed grains to dendritic grains from lower area to EH affected surface. After EH treatment, the microhardness generally increased with a maximum increase of ∼67% within 5 mm from EH affected surface, the tensile yield stress increased from 320 MPa to maximum of 700 MPa. The strengthening mechanism is different at various depth positions: near EH affected surface, the main strengthening mechanism is high-density dislocations, stacking faults and grain refinement; in areas relatively far from EH affected surface, only dislocation structure contributed to the strengthening of mechanical properties.

Plain-woven carbon fiber-reinforced plastic (PW-CFRP) exhibits high damage tolerance and is widely used in the aerospace field. To address the issue that single-scale drilling simulation is difficult to reflect the practical drilling force due to the change in material elastic properties in PW-CFRP drilling simulation, this paper studies the prediction of elastic properties of PW-CFRP and multi-scale three-dimensional drilling simulation. Based on the prediction model of elastic performance parameters with periodic boundary conditions, the three-dimensional drilling simulation of PW-CFRP is carried out using the predicted material elastic performance parameters and the multi-scale finite element method, with experimental verification. The results show that the finite element method based on periodic boundary conditions can accurately predict the elastic constants of braided composites. For the woven unit cell, its boundary surface changes from plane to surface under shear load, and convex-concave warping deformation occurs. The PW-CFRP three-dimensional drilling simulation model, based on the stiffness prediction model, can accurately predict the axial force and torque during the drilling process. Under the same process parameters, the maximum relative errors between the simulation prediction and the experimental results of the drilling thrust force and torque are 14.2% and 8.5%, respectively. The multi-scale drilling simulation of PW-CFRP, from microscopic to mesoscopic to macroscopic, is realized.

Abstract Hypoxia is an essential hallmark of solid tumors and HIF1α is a central regulator of tumor cell adaptation and survival in the hypoxic environment. In this study, we explored the biological functions of cell cycle division-related gene 8 (CDCA8) in bladder cancer (BCa) cells in the hypoxic settings. Specifically, we found that CDCA8 was significantly upregulated in BCa cell lines and clinical samples and its expression was positively correlated with advanced BCa stage, grade, and poor overall survival (OS). The expression of CDCA8 proteins was required for BCa cells to survive in the hypoxic condition. Mechanistically, CDCA8 stabilizes HIF1α by competing with PTEN for AKT binding, consequently leading to PTEN displacement and activation of the AKT/GSK3β signaling cascade that stimulates HIF1α protein stability. Significantly, HIF1α proteins bind to CDCA8 promoter for transcriptional activation, forming a positive-feedback loop to sustain BCa tumor cells under oxygen-deficient environment. Together, we defined CDCA8 as a key regulator for BCa cells to sense and prevail oxygen deprivation and as a novel BCa therapeutic target.

Abstract Background We assessed health-related quality of life (HRQOL) and its determinants among rural glaucoma participants compared to age-matched normal controls in the population-based Handan Eye Study (HES), in rural Yongnian County, northern China. Methods We enrolled 99 adults with glaucoma (mean age 63.0 ± 11.0 years), including primary open-angle glaucoma (POAG, n = 67) and primary angle-closure glaucoma (PACG, n = 32) and 102 controls (mean age 58.5 ± 5.3 years) with normal visual acuity and visual field and no history of glaucoma. Results of ophthalmic examinations and socioeconomic data were recorded. HRQOL was measured using the EQ-5D (converted to utility valves, UVs), and visual function (VF) and vision-related quality of life (VRQOL) were evaluated using the visual function-quality of life (VF-QOL) instrument. Primary and secondary outcome measures EQ-5D and VF-QOL scores. Results The mean UVs, VF, and VRQOL scores for glaucoma cases were 0.98 ± 0.04, 87.9 ± 15.2, and 95.5 ± 12.8, respectively, significantly worse than VF (94.4 ± 4.4) and VRQOL (100.0 ± 0.0) among controls, even after adjusting for age, gender, educational level, and family income (P = 0.015, P = 0.033). UVs were significantly lower among glaucoma participants with impaired VRQOL (55.4 ± 11.5) compared to those with normal VRQOL scores (99.1 ± 2.8) (UVs: 0.92 ± 0.08 vs. 0.99 ± 0.03, P = 0.036), also after adjustment for age and family income (P = 0.006). Participants with PACG had significantly lower VF and VRQOL scores compared to POAG (77.8 ± 21.4 vs. 92.9 ± 6.8, P

Introduction: Gypenoside is a natural extract of Gynostemma pentaphyllum (Thunb.) Makino, a plant in the Cucurbitaceae family. It has been reported to have antitumor effects on the proliferation, migration and apoptosis of various types of cancer cells. However, the use of gypenoside in the treatment of gastric cancer has not been studied. In the present study, we explored the therapeutic effect of gypenoside on gastric cancer and the potential molecular mechanism.Methods and Results: Our results showed that gypenoside induced apoptosis in HGC-27 and SGC-7901 cells in a time-dependent and dose-dependent manner. Network pharmacology analyses predicted that gypenoside exerts its therapeutic effects through the PI3K/AKT/mTOR signaling pathway. Furthermore, molecular docking and western blot experiments confirmed that gypenoside induced the apoptosis of gastric cancer cells through the PI3K/AKT/mTOR signaling pathway. In addition, network pharmacological analysis revealed that the common targets of gypenoside in gastric cancer were enriched in the immune effector process, PD-L1 expression, the PD-1 checkpoint pathway, and the Jak-STAT signaling pathway. Furthermore, molecular docking and western blot assays demonstrated that gypenoside could bind to STAT3 and reduce its phosphorylation. Thus, the transcription of PD-L1 was inhibited in gastric cancer cells. Moreover, coculture experiments of gastric cancer cells with gypenoside and primary mouse CD8+ T cells showed that gastric cancer cells treated with gypenoside could enhance the antitumor ability of T cells. Animal experiments confirmed the antitumor effect of gypenoside, and the expression of PD-L1 was significantly downregulated in the gypenoside-treated group.Conclusion: Gypenoside induced the apoptosis of gastric cancer cells by inhibiting the PI3K/AKT/mTOR pathway and simultaneously inhibited the expression of PD-L1 in gastric cancer cells, thus enhancing the antitumor immunity of T cells. This study provides a theoretical basis for applying gypenoside as a new therapeutic agent to enhance the efficacy of immunotherapy in gastric cancer.

Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh.cib-5D.1 for Gh) were attributed to the famous genes, Rht-D1 and Pina, respectively, indicating that the correlation of involved traits was supported by the pleotropic or linked genes. Notably, a novel major stable QTL for Gh was detected in the C12, QGh.cib-7D, with ZKM138-derived allele increasing grain hardness, which was simultaneously mapped by the BSE-Seq method. The geographic pattern and transmissibility of this locus revealed that the increasing-Gh allele is highly frequently present in 85.79% of 373 worldwide wheat varieties and presented 99.31% transmissibility in 144 ZKM138-derivatives, indicating the non-negative effect on yield performance and that its indirect passive selection has happened during the actual breeding process. Thus, the contribution of this new Gh-related locus was highlighted in consideration of improving the efficiency and accuracy of the soft/hard material selection in the molecular marker-assisted process. Further, TraesCS7D02G099400, TraesCS7D02G098000, and TraesCS7D02G099500 were initially deduced to be the most potential candidate genes of QGh.cib-7D. Collectively, this study provided valuable information of elucidating the genetic architecture of Gh for wheat quality improvement.

High pressure is an effective means to optimize the thermoelectric (TE) performance by sharply improving the electrical properties of materials. Studying the carrier effective mass (m*) is a feasible way to uncover the basic reason for superior electrical properties under high pressure. However, it is still difficult to obtain the m* under pressure in experiments. Thus, in this work, the m* of α-PbSe (Fm3̄m) under high pressure is calculated by band dispersion relation based on the density functional theory. It is found that the high pressure decreases m* of α-PbSe, which is the cause for excellent electrical properties. Moreover, the isotropy of m* enhances with the increase in the pressure, which means the high pressure further optimizes the isotropy of the carrier migration in the structure. It is reveled that the higher the pressure, the more beneficial to improve the electrical properties of α-PbSe, thus optimizing the TE performance before the phase transition pressure (4.5 GPa). This work is of great significance for exploring the mechanism of in situ high-pressure TE properties in the future, as well as the prediction and selection of high-performance TE materials under high pressure.

Catalyst layers (CLs) of proton exchange membrane fuel cells (PEMFCs) where the electrochemical reactions take place have a critical effect on the cell performance and liquid water forming in CLs during operation can influence the reactive transport processes which is challenge for experimental observation due to the temporal and spatial limitation. In this study, nanoscale structures of CLs in PEMFCs are reconstructed with pores, carbon, platinum (Pt) particles, and ionomers fully resolved. Distributions of liquid water with different saturations and wettabilities within nanoscale structures are simulated by the lattice Boltzmann method. Pore-scale modeling of oxygen reactive transport in the nanoscale structures is implemented, with oxygen diffusion in pores and ionomers, as well as an electrochemical reaction at the Pt surface considered. Effects of liquid water on the pore size distribution, electrochemical area, and oxygen concentration distribution are discussed. Liquid water in hydrophilic CL tends to form a film covering the reactive sites, while that in hydrophobic CL forms a droplet preferentially occupying large pores. For the hydrophilic case, local transport resistance increases significantly under a low saturation, while for the hydrophobic case, a remarkable increase in the local transport resistance can only be found after liquid water saturation higher than 0.8. Finally, the conjecture that liquid water in pores with a size smaller than a threshold pore size can conduct protons is considered. Different values of the threshold pore size are studied. The results show that when the threshold value is greater than 10 nm, the local transport resistance will decrease as the liquid water saturation increases, which means the optimizing strategy of CL needs to carefully consider the effects of liquid water.

Most of the current studies on the flood susceptibility of the Tibetan Plateau (TP) have relied on historical observations, lacking future projections and are not conductive to adaptive strategy optimization. Here, we examine the dynamics of flood susceptibility using a logistic regression model. When combined with climate and land use changes, the flood susceptibility in the TP is projected to increase under three Shared Socioeconomic Pathways (SSP). By the 2090 s, compared to the baseline period (1960–2020), the areas classified as very highly susceptible will experience an increase of 3.63 %, 6.17 %, and 15.26 % under the SSP126, SSP245, and SSP585 scenarios, respectively. The regions with high (4.98 %) and very high (6.88 %) flood susceptibility are primarily concentrated in densely populated areas located in the eastern and southern parts of the TP. As significant factors influencing flood susceptibility, the mean annual precipitation in the TP is expected to increase by 114 mm, 135 mm, and 223 mm from the baseline to the 2090 s under the SSP126, SSP245, and SSP585 scenarios, respectively. Additionally, the mean annual temperature is projected to rise by 2.2 ℃, 3.5 ℃, and 7.1 ℃, respectively. Furthermore, there will be a substantial expansion in the built-up area within the TP, with the percentage of built-up area increasing from 0.12 % in 2020 to 0.32 % by 2095. Our findings provide a quantitative assessment of how both natural environmental factors and human disturbances contribute to the susceptibility of the TP to flooding. Moving forward, it is expected that the built-up area on the northeastern edge of the TP will experience significant growth, resulting in an increased vulnerability to floods. Therefore, it is imperative to implement rational land use and land cover planning measures in order to mitigate the impact of flood disasters.

Abstract Desmoplastic small round-cell tumors (DSRCT) frequently develop in the retroperitoneum, pelvis, omentum, and mesentery. Here, we present an unusual case of primary DSRCT in the liver. The patient was an 11-year-old boy with multiple solid masses in the liver parenchyma. The tumor in the needle biopsy had a histology revealing a small round cell morphology and desmoplasia. It shows the immunohistochemical features of DSRCT and documentation of EWSR1-WT1 fusion. A potential diagnostic pitfall is exerted when evaluating liver biopsy, in which DSRCT is a great mimicker and may be easily confused with more common liver malignancies of childhood, such as hepatoblastoma, calcifying nested stromal-epithelial tumor, undifferentiated embryonal sarcoma, and other small round cell tumors, as well as the fibrolamellar variant of hepatocellular carcinoma. This distinction is critical because an accurate therapeutic approach requires a correct diagnosis.

Abstract The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

Explosive welding interface commonly show wavy shapes, makes microstructure anisotropic. The effects of microstructure and different loading directions on shear properties of bonding interfaces at dynamic loading conditions are still unclear. In this work, characteristics on transverse and longitudinal sections of TA2/Q235 welding interface was characterized by optical microscopy. It was found that the transverse sections of bonding interface showed wavy shapes with wavelength and amplitude of 1200 μm and 400 μm. The longitudinal sections of bonding interfaces were composed of wavy interface, dislocation shaped interface and stacking fault shaped interface, which was explained by non-equilibrium theory. A small-size S-shaped specimens was processed to investigate shear properties of bonding interface varied with orientation angles (0°, 45°and 90°) at both quasi-static (0.001 s−1) and dynamic (5000∼7000 s−1) loadings. Meanwhile, fracture mechanism of interfaces was analyzed by scanning electron microscopy coupled with energy dispersive spectrometer. The results indicated that the maximum shear strength of joining interfaces (380 MPa–410 MPa under quasi-static loading, and 450 MPa–600 MPa under dynamic loading) was obtained along 90° orientation angle. Fluctuation of explosive detonation pressure was the fundamental cause of the interface inhomogeneity, and strength of joining interfaces increases with increasing strain rates, indicating positive strain rate sensitivity. Fracture mainly occurred in bonding interfaces near TA2 side at quasi-state loading, and failure occurred in interface waves at dynamic loading because of TA2 showed more obvious strain rate sensitivity than Q235. Fracture morphology indicated the ductile-brittle mixed fracture occurred in both quasi-static and dynamic tests.

Abstract The safety and immunogenicity of a protein-based tetravalent vaccine SCTV01E that contains spike protein ectodomain (S-ECD) of Alpha, Beta, Delta and Omicron BA.1 are assessed and compared with bivalent protein vaccine SCTV01C (Alpha and Beta variants) and monovalent mRNA vaccine (NCT05323461). The primary endpoints are the geometric mean titers (GMT) of live virus neutralizing antibodies (nAb) to Delta (B.1.617.2) and Omicron BA.1 at day 28 post-injection. The secondary endpoints include the safety, day 180 GMTs against Delta and Omicron BA.1, day 28 GMTs to BA.5, and seroresponse rates of neutralizing antibodies and T cell responses at day 28 post-injection. 450 participants, comprising of 449 males and 1 female, with a median age (range) of 27 (18–62) years, are assigned to receive one booster dose of BNT162b2, 20 µg SCTV01C or 30 µg SCTV01E and completed 4-week follow-up. All SCTV01E related adverse events (AEs) are mild or moderate and no Grade ≥3 AE, serious AE or new safety concerns are identified. Day 28 GMT of live virus neutralizing antibodies and seroresponse against Omicron BA.1 and BA.5 with SCTV01E are significantly higher than those with SCTV01C and BNT162b2. These data indicate an overall neutralization superiority with tetravalent booster immunization in men.

Proton exchange membrane fuel cells are devices that directly convert chemical energy to electricity. A hydrogen oxidation reaction takes place on the anode side, generating protons and electrons. In the cathode, oxygen reduction reaction involving oxygen, proton and electron occurs, producing water and heat. The water content in PEMFCs should be maintained at a reasonable amount to avoid water flooding or membrane dehydration. The thermal management and water management of PEMFCs are important for an efficient and stable operation of PEMFCs. Inside the multiscale spaces of PEMFCs, multiphase flow with a phase change, heat and mass transfer, proton and electron conduction, and electrochemical reaction simultaneously take place, which play important roles in the performance, lifetime and cost of PEMFCs. These processes should be well understood for better designing PEMFCs and improving the thermal management and water management.

A smart response fluid was designed and developed to overcome the challenges of gas channeling during CO2 flooding in low-permeability, tight oil reservoirs. The fluid is based on Gemini surfactant with self-assembly capabilities, and the tertiary amine group serves as the response component. The responsive characteristics and corresponding mechanism of the smart fluid during the interaction with CO2/oil were studied, followed by the shear characteristics of the thickened aggregates obtained by the smart fluid responding to CO2. The temperature and salt resistance of the smart fluid and the aggregates were evaluated, and their feasibility and effectiveness in sweep-controlling during the CO2 flooding were confirmed. This research reveals: (1) Thickened aggregates could be assembled since the smart fluid interacted with CO2. When the mass fraction of the smart fluid ranged from 0.05% to 2.50%, the thickening ratio changed from 9 to 246, with viscosity reaching 13 to 3100 mPa·s. As a result, the sweep efficiency in low-permeability core models could be increased in our experiments. (2) When the smart fluid (0.5% to 1.0%) was exposed to simulated oil, the oil/fluid interfacial tension decreased to the level of 1×10−2 mN/m. Furthermore, the vesicle-like micelles in the smart fluid completely transformed into spherical micelles when the fluid was exposed to simulated oil with the saturation greater than 10%. As a result, the smart fluid could maintain low oil/fluid interfacial tension, and would not be thickened after oil exposure. (3) When the smart fluid interacted with CO2, the aggregates showed self-healing properties in terms of shear-thinning, static-thickening, and structural integrity after several shear-static cycles. Therefore, this fluid is safe to be placed in deep reservoirs. (4) The long-term temperature and salt resistance of the smart fluid and thickened aggregates have been confirmed.

Abstract Background Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM. Methods Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m2 ≤ BMI

Poor wind conditions in metropolitan areas can result in inadequate ventilation and degradation of the thermal environment. Several researches have demonstrated that the building ground floor elevation (BGFE) enhances the wind conditions surrounding buildings. Further investigation is required to thoroughly examine the BGFE’s impact on the wind conditions in the courtyard area. We researched how the various overhead placements affect the ventilation of a U-shaped school building’s courtyard space in different wind directions. We performed Computational Fluid Dynamics (CFD) numerical simulation experiments on 93 overhead scenarios based on field measurements and validation. The statistical analysis of the experimental data revealed that the BGFE had significant effects on reducing the mean air age (p < 0.001), standard deviation of air age (p < 0.01), standard deviation of wind speed (p < 0.001), and mean wind speed (p < 0.01) in the courtyard space. The BGFE in the northeastern zone of the U-shaped school building significantly increased the mean air age (p < 0.05), while the BGFE in the middle and southwestern zones significantly decreased the mean air age (p < 0.001), and the BGFE in the southeastern zone significantly decreased the mean wind speed (p < 0.05). The BGFE facilitates the entry of fresh air and offers even ventilation while significantly reducing wind speed. Choose sites C and D to enhance the U-shaped courtyard’s ventilation and avoid locations B and E. This paper’s findings provide theoretical guidance for designing the elevation of courtyard space from a ventilation perspective and for the green rehabilitation of existing buildings.

A comprehensive and precise evaluation of Arthropoda diversity in agricultural landscapes can enhance biological pest control strategies. We used Malaise traps and sweep nets to collect insects from three double-cropping paddy fields. DNA was extracted from the ethanol preservative of the Malaise traps and from tissue samples of selected parasitoid wasps. This was followed by amplification using DNA barcoding primers to prepare high-throughput sequencing libraries. We annotated a total of 4956 operational taxonomic units (OTUs), encompassing 174 genera and 32 families of parasitoid wasps. The ethanol filter method efficiently captured a wide range of information. However, the method has low resolution and may result in a reduced estimate of species abundance. Additional insect species were also identified in the parasitoid samples. This suggests that high throughput sequencing from adult parasitoid wasps can also detect host species, enabling a better understanding of host species and providing insights into food webs.

The first quantum revolution has brought us the classical Internet and information technology. Today, as technology advances rapidly, the second quantum revolution quietly arrives, with a crucial moment for quantum technology to establish large-scale quantum networks. However, solid-state quantum bits (such as superconducting and semiconductor qubits) typically operate in the microwave frequency range, making it challenging to transmit signals over long distances. Therefore, there is an urgent need to develop quantum transducer chips capable of converting microwaves into optical photons in the communication band, since the thermal noise of optical photons at room temperature is negligible, rendering them an ideal information carrier for large-scale spatial communication. Such devices are important for connecting different physical platforms and efficiently transmitting quantum information. This paper focuses on the fast-developing field of optomechanical quantum transducers, which has flourished over the past decade, yielding numerous advanced achievements. We categorize transducers based on various mechanical resonators and discuss their principles of operation and their achievements. Based on existing research on optomechanical transducers, we compare the parameters of several mechanical resonators and analyze their advantages and limitations, as well as provide prospects for the future development of quantum transducers.

Opioid withdrawal generates extremely unpleasant physical symptoms and negative affective states. A rapid relief of opioid withdrawal-induced anxiety has obvious clinical relevance but has been rarely reported. We have shown that injection of ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) leads to a rapid alleviation of anxiety-like behaviors in male mice undergoing chronic morphine withdrawal. Here we investigated the contribution of nucleus accumbens shell (sNAc) parvalbumin (PV)-neurons to this process. Chronic morphine withdrawal was associated with higher intrinsic excitability of sNAc PV-neurons via reduced voltage-dependent potassium currents. Chemogenetic inhibition of sNAc PV-neurons reversed the enhanced excitability of PV-neurons and anxiety-like behaviors in these morphine withdrawal male mice, while activation of sNAc PV-neurons induced anxiety-like behaviors in naive male mice. (2R,6R)-HNK reversed the altered potassium currents and intrinsic excitability of sNAc PV-neurons. Our findings demonstrate an important contribution of sNAc PV-neurons to modulating morphine withdrawal-induced anxiety-like behaviors and rapid relief of anxiety-like behaviors by (2R,6R)-HNK, this newly identified target may have therapeutic potentials in treating opioid addiction and anxiety disorders.

Abstract The Warburg effect‐related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation‐induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha‐ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex‐I (MHC‐I) antigen processing and presentation, as well as the expression of β2‐microglobulin (B2M). While αKG modulates broad‐spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD‐1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti‐tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC.

Abstract Objective Mind‐wandering (MW) is defined as a shift of attention from external tasks toward internal thoughts and is popularly measured by the sustained attention to response task (SART). SART is able to capture MW, but cannot track the dynamics of mind‐wandering over time well. We thus attempted to modify the sustained attention to response task paradigm (mSART) to capture the participant's mind‐wandering state over time and quantify the degree of mind‐wandering using the current behavioral data. Methods 179 participants from Wenzhou Medical University were recruited to participate in this experiment. The main changes to the experiment included (1) manipulating different no‐go stimuli frequencies to control the difficulty of the task and setting 9 modes; (2) extending the experiment time to 30 min; (3) allowing participants to correct errors by pressing the b key. Error rate, Mean RTs, RT CV, and d' were used to reflect MW. Analysis of covariance (ANCOVA) was performed. Results ANOVA was used to explore Mean RTs, RT CV and d’ for participants with different levels of mind‐wandering and significant differences were found (Mean RTs:Welch's F (2, 8606.04) = 579.00, p

Abstract The aim of this study is to investigate the fluid flow structure and heat transfer from an isothermal cylinder with a curved corner radius ratio (r/R) of 0.5, and attack angle (α) is varied between 0° ≤ α ≤ 45°. The cylinder is subjected to airflow at a Reynolds number (Re) = 180 and Prandtl number (Pr) = 0.7. This study focuses on the effect of α on the fluid forces, Strouhal number, Nusselt number, and flow structure, and wake bubble size. The sensitivity of the time-mean drag and lift forces is investigated to α, and they appear to be minimum at critical α of 5° and 12°, respectively. The increase of α from 0 to 45° results in about 12.9% enhancement in the heat transfer from the cylinder.

Abstract Thermal errors are one key impact factor on the processing accuracy of numerical control machine. This study targeted at a certain vertical processing center presents a new algorithm for predictive modeling of thermal errors in numerical control machine. This algorithm is founded on back-propagation neural networks (BPNNs) and adopts beetle antennae search (BAS) to find the best weights and thresholds of BPNNs. It avoids the local minimization due to local extremums faced by traditional BPNNs. The intermingling rate and arithmetic computation efficiency of neural network algorithms are further improved. Then, a BAS-BP thermal error prediction model is built with the machine temperature changes and thermal errors as the input data. Compared with conventional BPNNs, the BPNN after particle swarm optimization suggests the convergence rate of BAS-BP is improved by 85%, the leftover mistakes between the genuine information and the anticipated information are under 1 um, and the overall prediction precision is above 90%. Thus, the new model has high precision, high anti-disturbance ability and strong robustness.

Abstract Quantum teleportation can transfer an unknown quantum state between distant quantum nodes, which holds great promise in enabling large-scale quantum networks. To advance the full potential of quantum teleportation, quantum states must be faithfully transferred at a high rate over long distance. Despite recent impressive advances, a high-rate quantum teleportation system across metropolitan fiber networks is extremely desired. Here, we demonstrate a quantum teleportation system which transfers quantum states carried by independent photons at a rate of 7.1 ± 0.4 Hz over 64-km-long fiber channel. An average single-photon fidelity of ≥90.6 ± 2.6% is achieved, which exceeds the maximum fidelity of 2/3 in classical regime. Our result marks an important milestone towards quantum networks and opens the door to exploring quantum entanglement based informatic applications for the future quantum internet.

Abstract The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.