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Terahertz (THz) waves have exhibited promising prospects in 6G/7G communications, sensing, nondestructive detection, material modulation, and biomedical applications. With the development of high-power THz sources, more and more nonlinear optical effects at THz frequency and THz-induced nonlinear optical phenomena are investigated. These studies not only show a clear physics picture of electrons, ions, and molecules but also provide many novel applications in sensing, imaging, communications, and aerospace. Here, we review recent developments in THz nonlinear physics and THz-induced nonlinear optical phenomena. This review provides an overview and illustrates examples of how to achieve strong THz nonlinear phenomena and how to use THz waves to achieve nonlinear material modulation.

ObjectiveTo investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer. MethodsA total of 48 BRCA mutation carriers (16 with BRCA1 and 32 with BRCA2) and 78 age-matched non-carriers were included in this study. Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues. The FOXP3 RNA expression in 39 BRCA1, 36 BRCA2, and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombination deficiency scores were evaluated to validate the immunohistochemistry results. ResultsThe FOXP3 positive rate was 43.8% (7/16) in BRCA1 mutation carriers, 59.4% (19/32) in BRCA2 mutation carriers, and 9.0% (7/78) in non-carriers. The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers (P=0.002; P

Abstract The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Abstract Confronted with the concurrent challenges of economic advancement and environmental management, this study explores whether implementing Intellectual Property Demonstration Policies (IPDP) can be a covert force in enhancing carbon emission efficiency. Utilizing panel data from 280 prefecture-level cities in China over the period 2007–2019, we employ a quasi-natural experimental design, incorporating multiple-period difference-in-differences models, mediation effect models, and spatial Durbin difference-in-differences models to assess the impacts of IPDP on carbon emission efficiency, its mechanisms of action, and its spatial spillover effects. The regression results of the multi-period difference-in-differences model reveal a statistically significant enhancement in carbon emission efficiency due to IPDP, with an impact coefficient of 0.044. Through heterogeneity tests, it is observed that the influence of IPDP on carbon emission efficiency varies based on regional characteristics, carbon emission levels, and the extent of marketization. The mediation effect model demonstrates that IPDP enhances carbon emission efficiency by fostering green technological innovation and facilitating the transformation of industrial structures. Furthermore, the spatial Durbin difference-in-differences model illustrates that IPDP positively influences the carbon emission efficiency of neighboring regions, indicating favorable spatial spillover effects. Notably, the indirect effect coefficients in the geographical distance matrix, economic distance matrix, and economic-geographical nested matrix are calculated as 0.673, 0.250, and 0.386, respectively. These findings offer compelling theoretical and empirical support for strengthening the intellectual property framework to optimize its environmental impact.

Mixed matrix membranes (MMMs) could combine the advantages of both polymeric membranes and porous fillers, making them an effective alternative to conventional polymer membranes. However, interfacial incompatibility issues, such as the presence of interfacial voids, hardening of polymer chains, and blockage of micropores by polymers between common MMMs fillers and the polymer matrix, currently limit the gas separation performance of MMMs. Ternary phase MMMs (consisting of a filler, an additive, and a matrix) made by adding a third compound, usually functionalized additives, can overcome the structural problems of binary phase MMMs and positively impact membrane separation performance. This review introduces the structure and fabrication processes for ternary MMMs, categorizes various nanofillers and the third component, and summarizes and analyzes in detail the CO2 separation performance of newly developed ternary MMMs based on both rubbery and glassy polymers. Based on this separation data, the challenges of ternary MMMs are also discussed. Finally, future directions for ternary MMMs are proposed.

ABSTRACT Riverine islands are widespread alluvium wetlands developed in large rivers, and bacterial communities are crucial to their ecological function, yet their assembly processes are rarely addressed. The ecosystem services provided by the middle and the lower Yangtze are primarily threatened by pollution discharge from agricultural land use, and resource overutilization (e.g., embankments), respectively. Here, we assessed bacterial community assembly processes and their drivers within riverine islands in the middle Yangtze River (MR islands) and those in the lower reach (LR islands). A significant distance–decay relationship was observed, although the turnover rate was lower than that of the terrestrial ecosystem with less connectivity. Deterministic and stochastic processes jointly shaped community patterns, and the influence of stochastic increased from 26% in MR islands to 59% for those in LR islands. Meanwhile, the bacterial community in MR islands was controlled more by inorganic nitrogen availability, whereas those in LR islands were governed by pH and EC, although those factors explained a limited fraction of variation in the bacterial community. Potential indicator taxa (affiliated with Nocardioides and Lysobacter) characterized the waterway transport pollution. Overall, our study demonstrated that bacterial community dissimilarity and the importance of dispersal limitation increased concurrently along the flow direction, while distinct local factors further determined bacterial community compositions by selecting habitat-specificity taxa and particularly metabolism function. These findings enhanced our understanding of the mechanisms driving changes in bacterial communities of riverine islands subject to increased anthropogenic impacts.IMPORTANCERivers are among the most threatened ecosystems globally and face multiple stressors related to human activity. However, linkages between microbial diversity patterns and assembly processes in rivers remain unclear, especially in riverine islands developed in large rivers. Our findings reveal that distinct factors result in divergent bacterial community compositions and functional profiles in the riverine islands in the middle Yangtze and those in the lower Yangtze, with substantial differentiation in deterministic and stochastic processes that jointly contribute to bacterial community assemblages. Additionally, keystone species may play important metabolic roles in coping with human-related disturbances. This study provides an improved understanding of relationships between microbial diversity patterns and ecosystem functions under environmental changes in large river ecosystems.

Abstract In the rate‐state friction law framework, the transition from velocity weakening (V‐W) to velocity strengthening (V‐S) behavior marks the base of the seismogenic crust. Here we investigate the role of fault slip displacement under hydrothermal conditions in controlling the V‐W to V‐S transition. We shear simulated gabbro gouges at slip velocities ranging from 16 nm/s (∼50 cm/year) to 10 μm/s (∼8 cm/day) under hydrothermal conditions (300–400°C temperature; 30 MPa pore fluid pressure). We observe that cumulative fault slip increases the critical velocity for the V‐W to V‐S transition. The transition is accompanied by localized to distributed deformation mode, the formation of smectite‐type clays and occurrence of intergranular mass transfer. Our results provide insights into understanding the deepening and shallowing of V‐W/V‐S boundary (lower limit of the seismogenic zone) following a mainshock. Besides strain rate effects, slip‐enhanced chemical alteration and grain size‐sensitive deformation may temporarily contribute to the shallowing process.

In fourth-generation reactors, fast reactors characterized by high average neutron flux, proliferating fission nuclear fuel, and transmutation of long-decay actinides have become the primary research focus in China. NECP-SARAX is an advanced reactor neutron analysis and calculation system independently developed by the Nuclear Engineering Computational Physics Laboratory of Xi'an Jiaotong University. Based on the features and functions of NECP-SARAX, Xi'an Jiaotong University has developed a customized LoongSARAX system specifically for core physical engineering design and safety evaluation of liquid metal cooled fast reactors. LoongSARAX includes cross-section generation module TULIP and core steady-state analysis module LAVENDER. TULIP is used for the calculation of uniform assemblies, and for addressing one-dimensional plate and cylinder problems. LAVENDER is used for the 3-D core calculation for advanced reactor neutron analysis systems. After obtaining the few-group cross sections for each assembly, LAVENDER employs multi-group neutron transport methods to calculate the core's primary parameters. LAVENDER calculates a variety of parameters for liquid metal cooled fast reactor cores, including criticality, power distribution, reactivity, burnup, etc. In the course of software development, discrepancies between the results obtained through software calculations and actual results are inevitable. If LoongSARAX is to be applied to engineering practice, it is indispensable to ensure its normative and systematic verification and validation (V&V). Relevant international data on the physical calculation benchmark of liquid metal cooled fast reactor were collected and collated in this paper, with a focus on the V&V of LoongSARAX. On this basis, the V&V matrix for the LoongSARAX program was established. In order to improve the accuracy of verification, the whole program was divided into different modules for module verification, subsystem verification and system verification respectively. LoongSARAX was referred to as the system, with TULIP and LAVENDER being its subsystems. The V&V process begins with modules in TULIP and LAVENDER, followed by the system as a whole. The V&V of LoongSARAX covers fast reactors with sodium and lead coolants, such as JOYO, ZPPR17A, FFTF, BFS, etc. By comparing the calculation results of LoongSARAX with the experimental measurement results or MCNP results in the benchmark reports, it can be clearly concluded that LoongSARAX has high calculation accuracy and reliability in the field of liquid metal cooled fast reactor. In summary, LoongSARAX, a computing system developed by Xi'an Jiaotong University for liquid metal cooled fast reactors, demonstrates excellent computing capabilities after undergoing rigorous and systematic V&V. This will provide strong support for the core physical engineering design and safety evaluation of liquid metal cooled fast reactors, and the application of LoongSARAX will also provide valuable experience for the development and promotion of fast reactors in the future.

Abstract Ultra-compact spectrometers are becoming increasingly popular for their promising applications in biomedical analysis, environmental monitoring, and food safety. In this work, we report a single-pixel-photodetector spectrometer with a spectral range from 480 nm to 820 nm, based on the AlGaAs/GaAs p-graded-n junction with a voltage-tunable optical response. To reconstruct the optical spectrum, we propose a tailored method called Neural Spectral Fields (NSF) that leverages the unique wavelength and bias-dependent responsivity matrix. Our spectrometer achieves a high spectral wavelength accuracy of up to 0.30 nm and a spectral resolution of up to 10 nm. Additionally, we demonstrate the high spectral imaging performance of the device. The compatibility of our demonstration with the standard III-V process greatly accelerates the commercialization of miniaturized spectrometers.

The dry reforming of CH4 (DRM) reaction can simultaneously convert two greenhouse gases CO2 and CH4 into high valued syngas. Nickel-based catalysts have been widely studied because of the low cost and high activity. However, carbon deposition making the deactivation of Ni-based catalyst is the main challenges for DRM reaction. This review illustrates DRM reaction mechanism and the causes of carbon deposition, as well as the resistance strategies of carbon deposition for Ni-based catalyst. The deposited carbon can be restrained by adjusting the size of Ni particles, introduction of promoters, reasonable design of support, controlling the reaction process and employing the confinement effect of the catalysts. The valuable insights are garnered for the further augmentation and optimization of the anti-carbon performance of catalysts by DFT and microkinetic. This work provides a tutorial for designing Ni-based catalysts with high anti-carbon deposition properties for DRM reaction.

After the resumption of work and production following the COVID-19 pandemic, many cities entered a “transition phase”, characterized by the gradual recovery of emission levels from various sources. Although the overall PM2.5 emission trends have recovered, the specific changes in different sources of PM2.5 remain unclear. Here, we investigated the changes in source contributions and the evolution pattern of pollution episodes (PE) in Wuhan during the “transition period” and compared them with the same period during the COVID-19 lockdown. We found that vehicle emissions, industrial processes, and road dust exhibited significant recoveries during the transition period, increasing by 5.4%, 4.8%, and 3.9%, respectively, during the PE. As primary emissions increased, secondary formation slightly declined, but it still played a predominant role (accounting for 39.1∼ 43.0% of secondary nitrate). The reduction in industrial activities was partially offset by residential burning. The evolution characteristics of PE exhibited significant differences between the two periods, with PM2.5 concentration persisting at a high level during the transition period. The differences in the evolution patterns of the two periods were also reflected in their change rates at each stage, which mostly depend on the pre-PE concentration level. The transition period shows a significantly higher value (8.4 μg m–3 h–1) compared with the lockdown period, almost double the amount. In addition to local emissions, regional transport should be a key consideration in pollution mitigation strategies, especially in areas adjacent to Wuhan. Our study quantifies the variations in sources between the two periods, providing valuable insights for optimizing environmental planning to achieve established goals.

The kidneys are susceptible to a range of insults that can cause damage to them. Early diagnosis, timely prevention, and proper treatment are crucial for improving the outcome of kidney injury. However, the complexity of renal structure and function makes it difficult to reach the demand of early detection and comprehensive evaluation of kidney injury. No successful drug therapy caused by the elaborate pathogenesis mechanism network of kidney injury calls for a systematical interpretation in mechanism researches. Recent advances in renal imaging and omics studies have provided novel views and deeper insights into kidney injury, but also raise challenges in reaching a comprehensive cellular and molecular atlas of kidney injury. Progresses in imaging and omics of kidney injury are being made in various directions, with the initiative of construction a high-resolution structural atlas of kidney, dynamic and non-invasive evaluation of renal function, and systematic establishment of spatially resolved molecular atlas by transcriptomics and metabolomics. With the limitations of a single modality, novel multimodal integration technologies of imaging and omics are being attempted to achieve a systematic description of nephropathy mechanisms. Further extensive efforts in renal multimodal imaging and omics studies are extremely required to deepen our understanding on kidney injury in the context of diagnostic, mechanistic and therapeutic perspectives.

Abstract Background Allergic diseases, including respiratory and food allergies, as well as allergic skin conditions have surged in prevalence in recent decades. In allergic diseases, the gut microbiome is dysbiotic, with reduced diversity of beneficial bacteria and increased abundance of potential pathogens. Research findings suggest that the microbiome, which is highly influenced by environmental and dietary factors, plays a central role in the development, progression, and severity of allergic diseases. The microbiome generates metabolites, which can regulate many of the host’s cellular metabolic processes and host immune responses. Aims and Methods Our goal is to provide a narrative and comprehensive literature review of the mechanisms through which microbial metabolites regulate host immune function and immune metabolism both in homeostasis and in the context of allergic diseases. Results and Discussion We describe key microbial metabolites such as short‐chain fatty acids, amino acids, bile acids and polyamines, elucidating their mechanisms of action, cellular targets and their roles in regulating metabolism within innate and adaptive immune cells. Furthermore, we characterize the role of bacterial metabolites in the pathogenesis of allergic diseases including allergic asthma, atopic dermatitis and food allergy. Conclusion Future research efforts should focus on investigating the physiological functions of microbiota‐derived metabolites to help develop new diagnostic and therapeutic interventions for allergic diseases.

Integrating Artificial Intelligence (AI) into education, particularly civic education, represents a transformative shift. This study explores the innovative fusion of AI with teaching methodologies, aiming to enhance educational outcomes and foster comprehensive student development. We construct a multidimensional civic education framework by employing theoretical and empirical approaches, examining the dynamics between educators, students, content, and pedagogical strategies. We assess student academic performance and behavior by utilizing the Multi-Task Classroom Behavior Recognition Network (MCBRN) and multivariate analysis of variance (ANOVA). Our findings reveal that the AI-enhanced teaching model significantly boosts student engagement and learning achievements in the experimental group, with behavior recognition accuracy reaching 96.9%. Moreover, these students demonstrated superior examination scores and overall competency levels compared to the control group (P

Freshwater aquaculture plays an important role in the global aquaculture industry. The success of freshwater aquaculture relies on the integration of bio-ecological remediation technologies to ensure its sustainable development. This paper systematically reviews the global literatures on bio-ecological remediation of freshwater aquaculture environments from 1990 to 2021, and discusses in detail the research progress and status quo in this field using both bibliometric analysis and content analysis. Our results indicate that the number of publications per year has increased year by year, with a particularly rapid increase after 2015. Institutions and researchers from China and the USA publish the greatest number of papers and contribute the most to this field. By analyzing the research progress in this field, we also find that the protection and restoration of freshwater aquaculture environments has received attention since as early as 1990, such as the application of constructed wetlands and recirculating aquaculture systems. Recently, researchers have increasingly focused on the use of microbial communities in remediation. Furthermore, vanRijn, J's papers are of great value to the research in this field. In content analysis, the application of primary technologies, including plant selection, aquatic animals, microorganisms, and biological filtration and purification equipment, as well as ecological engineering technologies with combinations of various types of organisms, is described to improve the effectiveness and efficiency of remediation. The performance, advantages, disadvantages, or limitations and prospects of these technology applications are analyzed in detail. By comparison, ecological engineering is shown to be the best remediation technology, being most comprehensive, and well-established. Taken together, this paper composes and summarizes existing work in this field, and provides guidance for future research on the improvement of existing technologies and the development of new technologies, with the aim of enhancing remediation capability, improving ecological sustainability and ensuring economic viability.

BackgroundProtein energy wasting (PEW) is common in patients on hemodialysis, and its development may involve gut microbial dysbiosis. However, the exact relationship between the composition of different flora and the development of PEW remains unclear.MethodsThis is an observational longitudinal study on 115 patients undergoing hemodialysis who were followed up for 1 year. All the patients were evaluated at baseline, and different microbiota compositions were determined. After a 1 year follow-up period, the correlations between clinical parameter variations and the relative abundance of different gut flora were assessed using Spearman correlation. Moreover, the associations of the abundance of different gut microbiota with decrease in lean tissue mass and the development of PEW were analyzed using ROC curve and logistical regression analyses.ResultsWe found that the relative abundances of Actinobacteria and Bifidobacteriaceae were significantly lower in patients with PEW than in those who did not develop PEW (p

This study presents a soft-rigid unified structure (SRUS) textile composed of an inorganic powder (IP) reinforced epoxy resin block (EIPB) array and a soft textile substrate via a pattern-controllable integrated molding method. The influence of IP content and alumina particle size on the cut and puncture resistance of the resulting SRUS textile was systematically investigated. Furthermore, the anti-puncture and anti-cutting mechanisms of the SRUS textile were comprehensively evaluated based on the analysis of damage morphology and process. The experimental results demonstrated a significant enhancement in the puncture and cut resistance of the SRUS textile upon the incorporation of IP. Moreover, the cut/puncture resistance of the SRUS textile increased with an increase in IP content and the size of Al2O3, and the optimal cut/puncture resistance was observed at 60 mesh-50 wt.%. Additionally, the anti-puncture mechanism of the SRUS textile was attributed to the presence of hard passivation at the EIPB, as well as friction self-locking at the gaps. The anti-cutting mechanism was ascribed to the reverse cutting action exerted by the hard particles on the blade, preventing further penetration. Overall, these findings provide valuable insights into the underlying mechanisms that contribute to its enhanced protective performance.

Artificial intelligence(AI) empowers the development of the medical industry, providing precise and intelligent assistance for clinical diagnosis, treatment, and rehabilitation.AI has the potential to facilitate shared decision making (SDM), but AI interventions used for SDM are currently in their infancy, presenting both challenges and opportunities. This paper aims to describe the application of AI in SDM, explore the problems and challenges of AI-based decision aid used for SDM, and propose possible solutions, aiming to provide a guide for the development and implementation of AI-based decision aid.

Molluscs do not have adaptive immune cells and corresponding antibodies in their bodies. They mainly rely on the innate immune system to protect themselves from various pathogens and foreign substances to maintain normal life activities. Pattern recognition receptors (PRRs) first sense pathogen-associated molecular patterns (PAMPs) during the innate immune response, triggering specific signaling pathways and resisting pathogenic invasion. Toll-like receptors (TLRs) are widely studied PRRs and play important roles in the innate immunity of invertebrates. The first TLR was found in Drosophila, which activated the transcription factor NF-κB signaling pathway to guide early embryonic development. Later, it was proved to play an important role in the immunity of Drosophila. A typical TLR protein includes three protein domains, the extracellular domain containing two to 45 leucine-rich repeats (LRRs), the transmembrane domain, and the intracellular region containing a TIR (Toll/interleukin-1 receptor) domain. According to their structure variation in the LRR extracellular domain, TLRs can be divided into two types, namely single cysteine cluster TLR (sccTLR) and multiple cysteine cluster TLR (mccTLR).The razor clam Sinonovacula constricta is an economically important bivalve species and one of the four traditional mariculture mollusks in China. However, deterioration of the rearing environment and various bacterial and viral disease outbreaks have caused significant economic losses to the S. constricta industry. Therefore, a deep understanding of the immune defense mechanisms in S. constricta would help implement effective disease resistance strategies. In this study, we identified all TLR genes in S. constricta using whole genomic resources. Firstly, we identified the S. constricta proteins with both TIR domain (PF01582) and LRR domain (PF13855) using the InterProScan. Secondly, we further searched the whole genome DNA sequence using the TBLASTN program and the TIR-LRR protein sequences as query to identify missed TLR genes during genome annotation. The TLR protein domains identified were analyzed with the SMART software (http://smart.embl-heidelberg.de/). The TLR proteins with incomplete domains were further corrected with the FGENESH+ program on the Softberry website (http://www.softberry.com/). Finally, a total of 42 S. constricta TLR (ScTLR) genes were identified. Among them, 33 genes encode typical TLR proteins with three domains, and the remaining nine genes encode TLR-like proteins lacking some domains. The typical S. constricta TLR proteins were classified into two types and four subtypes based on the protein domain structure characteristics. The type mccTLR includes one P-TLR and seven sPP-TLRs, while the type sccTLR includes 16 sP-TLRs and nine Ls-TLRs. Furthermore, the type and number of TLR genes were compared among ten species from four classes of mollusks, including S. constricta. The results showed that two types of TLR genes, V-type and Twin-TIR TLR, identified in other mollusks were not found in the S. constricta genome. The number of TLR genes varied dramatically between different species, wherein the owl limpet (Lottia gigantea) and the common octopus (Octopus sinensis) possessed 16 and 17 TLR genes, respectively, while the American oyster (Crassostrea virginica) owned more than 130 TLR genes. Even in the same taxonomic genus, different species had a vastly different number of TLR genes, such as the Pacific oyster (Crassostrea gigas), which belongs to the same genus as the American oyster, and possessed 83 TLR genes, obviously less than the American oyster. Evolutionarily, the anciently originated mccTLR genes in mollusks did not expand in number, while the recently originated sccTLR genes largely expanded in number. The qRT-PCR tissue-specific expression analysis showed that six TLR genes randomly selected were expressed in seven tissues, including the hemolymph, gill, hepatopancreas, gonad, foot, mantle, and siphon, being highly expressed in the hemolymph, gill, and hepatopancreas. Finally, the razor clams were infected with Vibrio parahemolyticus, and the gill and hepatopancreas tissues were collected at 12 h and 24 h post-injection (hpi) for further transcriptome analysis. The results showed that nine TLR genes were differentially expressed in the gill or hepatopancreas before and after V. parahemolyticus injection. Six genes (ctg118.25, ctg118.26, ctg356.25, ctg774.6, ctg681.6, and ctg1513.5) were differentially expressed in gill at 12 hpi or 48 hpi, in which only ctg1513.5 was down-regulated and the other five were up-regulated. Three genes (ctg467.9, ctg2496.3, and ctg903.17) were differentially expressed in the hepatopancreas at 12 hpi or 48 hpi, wherein ctg467.9 and ctg2496.3 were down-regulated, and ctg903.17 was up-regulated. In summary, our findings will pave the way for investigating the functions of TLR genes in the innate immune response to different pathogens.

Abstract Earthquakes often occur along faults in the presence of hot, pressurized water. Here we exploit a new experimental device to study friction in gabbro faults with water in vapor, liquid and supercritical states (water temperature and pressure up to 400 °C and 30 MPa, respectively). The experimental faults are sheared over slip velocities from 1 μm/s to 100 mm/s and slip distances up to 3 m (seismic deformation conditions). Here, we show with water in the vapor state, fault friction decreases with increasing slip distance and velocity. However, when water is in the liquid or supercritical state, friction decreases with slip distance, regardless of slip velocity. We propose that the formation of weak minerals, the chemical bonding properties of water and (elasto)hydrodynamic lubrication may explain the weakening behavior of the experimental faults. In nature, the transition of water from liquid or supercritical to vapor state can cause an abrupt increase in fault friction that can stop or delay the nucleation phase of an earthquake.

Abstract Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.

This paper presents an evaluation of the bearing capacity of cross-bracing in steel transmission tower structures. Design guidelines (ASCE 10-15, BS EN 50341-1, GB 50017-2017, and DL/T 5486-2020) related to the buckling capacity of the cross-bracing are summarized and compared with the experimental results. The current design provisions obtained the bearing capacity from the equivalent slenderness ratio, and then the stability coefficient and buckling capacity were derived. The calculated bearing capacity based on the design code tends to be overly progressive for smaller slenderness ratios (particularly those below 100), except for EN 50341-1-2012. Conversely, for larger slenderness ratios, ASCE 10-15 and DL/T 5486-2020 Class A design codes lean towards being overly progressive, while GB 50017-2017 and EN 50341-1-2012 codes tend to be more conservative. The design standard appears to exhibit unsafe predictions for Class A and B connections with low slenderness ratios and Class C connections. It needs to be noted that the effects of torsional stiffness and joint connection type are not considered in the current design codes, which are proved to be nonnegligible by the test results. In this paper, the bearing capacity calculation formula is proposed by introducing a modified effective length coefficient (K), and both the torsional stiffness and joint connection type are taken into account. The modified bearing capacity is verified with the test results; the correlation coefficient is 0.997, and the coefficient of variation is 0.04. It can provide a reference for the engineering design of steel lattice transmission tower structures.

As the fourth most important cancer management strategy except surgery, chemotherapy and radiotherapy, cancer immunotherapy has been confirmed to elicit durable antitumor effects in the clinic by leveraging the patient’s own immune system to eradicate the cancer cells. However, the limited population of patients who benefit from the current immunotherapies and the immune related adverse events hinder its development. The immunosuppressive microenvironment is the main cause of the failure, which leads to cancer immune evasion and immunity cycle blockade. Encouragingly, nanotechnology has been engineered to enhance the efficacy and reduce off-target toxicity of their therapeutic cargos by spatiotemporally controlling the biodistribution and release kinetics. Among them, lipid-based nanoparticles are the first nanomedicines to make clinical translation, which are now established platforms for diverse areas. In this perspective, we discuss the available lipid-based nanoparticles in research and market here, then describe their application in cancer immunotherapy, with special emphasis on the T cells-activated and macrophages-targeted delivery system. Through perpetuating each step of cancer immunity cycle, lipid-based nanoparticles can reduce immunosuppression and promote drug delivery to trigger robust antitumor response.

Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. In clinical treatments, the insensitivity of OS to conventional radiotherapy regimens significantly contributes to poor patient prognosis and survival. EXO1 is responsible for DNA repair pathways and telomere maintenance. Meanwhile, ATM and ATR are considered switches because they can regulate the expression of EXO1. However, their expression and interaction in OS cells under irradiation (IR) remain unclear. This study aims to investigate the roles of FBXO32, ATM, ATR and EXO1 in OS radiotherapy insensitivity and poor patient prognosis and explore potential pathogenic mechanisms. Bioinformatics is employed to analyse differential gene expression and correlations with prognosis in OS. Cell counting kit 8 assay, clone formation assay, and flow cytometry are used to evaluate cell survival and apopotosis under IR. Co-IP assay is used to detect protein‒protein interactions. Bioinformatics analysis reveals that EXO1 is closely related to survival, apoptosis and poor prognosis in OS. Silencing of EXO1 suppresses cell proliferation and increases the sensitivity of OS cells. Molecular biological experiments show that ATM and ATR act as switches to regulate EXO1 expression under IR. Higher expression of EXO1, which is closely correlated with IR insensitivity and poorer prognosis, might be used as a prognostic indicator for OS. Phosphorylated ATM enhances the expression of EXO1, and phosphorylated ATR induces the degradation of EXO1. More importantly, FBXO32 degrades ATR via ubiquitination in a time-dependent manner. Our data may provide a reference for future research in the mechanisms, clinical diagnosis, and treatment of OS.

Abstract Buildings near direct current transmission lines are sensitive to the electromagnetic environment, and the measurement of the electric field above them is important in engineering design and environmental assessment in China. The models of buildings and probes in the ion flow field were established to explore the accurate measurement method of the electric field above the building. Based on the upstream finite element method and the predictor–corrector method, the influence of whether the probe was grounded or not above the building was studied. On this basis, simulation experiments and real‐type experiments were carried out. The results show that when the electrical conductivity of the building was greater than 10−10 S/m, being grounded or not would not change the results. When the building conductivity was between 10−11 and 10−12 S/m, the electric field measurement results would be increased by 30% to 120% after grounding. In the real‐type experiments on the platform with a plywood roof, the relative error in the electric field when grounded or not was only 2.6%. This proved the reliability of the calculated results. In this paper, the measuring method of the DC space charge‐modified electric field above buildings was analyzed first, and the conclusion that ground wire can be cancelled above buildings with general materials was presented. The research results can provide a technical basis for the accurate measurement of the electric field above the buildings near DC transmission lines.

Abstract Metabolic reprogramming is one of the main characteristics of cancer cells and plays pivotal role in the proliferation and survival of cancer cells. Amino acid is one of the key nutrients for cancer cells and many studies have focused on the regulation of amino acid metabolism, including the genetic alteration, epigenetic modification, transcription, translation and post-translational modification of key enzymes in amino acid metabolism. Long non-coding RNAs (lncRNAs) are composed of a heterogeneous group of RNAs with transcripts of more than 200 nucleotides in length. LncRNAs can bind to biological molecules such as DNA, RNA and protein, regulating the transcription, translation and post-translational modification of target genes. Now, the functions of lncRNAs in cancer metabolism have aroused great research interest and significant progress has been made. This review focuses on how lncRNAs participate in the reprogramming of amino acid metabolism in cancer cells, especially glutamine, serine, arginine, aspartate, cysteine metabolism. This will help us to better understand the regulatory mechanism of cancer metabolic reprogramming and provide new ideas for the development of anti-cancer drugs. Video Abstract

Objective Malnutrition commonly occurs in patients undergoing maintenance hemodialysis. Early detection of malnutrition could allow early interventions to prevent later complications. At present, there are not many biomarkers with high predictive value of end-stage kidney disease (ESKD)-related malnutrition, especially for early malnutrition in hemodialysis patients, which needs more in-depth research. Therefore, we performed a cross-sectional study on 97 patients to identify biomarkers for malnutrition in hemodialysis patients.Research Methods & Procedures 7-point subjective global assessment (SGA) was applied to evaluate the nutritional status of patients on hemodialysis. Serum levels of growth differentiation factor 15 (GDF15), albumin, pre-albumin, c-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), hemoglobin, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol were detected before hemodialysis. Logistic analysis and linear regression were used to analyze the association between GDF15 levels and the SGA score after adjustment for basic characteristics and laboratory findings.Results Among the 97 patients on hemodialysis, 51 had malnutrition (SGA < 6). There was no difference between the malnourished and well nourished (SGA ≥ 6) groups for dialysis duration, cholesterol, CRP, TNF-α, and hemoglobin. The malnutrition group had significantly lower grip strength (p

This paper presents experimental evidence of thermal pressurization (TP) weakening of seismic faults, and suggests TP processes could be significantly promoted by wear-induced sealing during earthquakes even for relatively permeable faults.

Objective: The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established. Methods: A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed. BRCA1/2 status was determined for all patients and relative risks (RRs) were calculated to evaluate cancer risk in relatives of the patients. Results: The incidences of breast cancer in female relatives of BRCA1 carriers, BRCA2 carriers, and non-carriers were 33.0%, 32.2%, and 7.7%, respectively. The corresponding incidences of ovarian cancer were 11.5%, 2.4%, and 0.5%, respectively. The incidences of pancreatic cancer in male relatives of BRCA1 carriers, BRCA2 carriers, and non-carriers were 1.4%, 2.7%, and 0.6%, respectively. The corresponding incidences of prostate cancer were 1.0%, 2.1%, and 0.4%, respectively. The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers (BRCA1: RR = 4.29, P < 0.001 and RR = 21.95, P < 0.001; BRCA2: RR = 4.19, P < 0.001 and RR = 4.65, P < 0.001, respectively). Additionally, higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers (RR = 4.34, P = 0.001 and RR = 4.86, P = 0.001, respectively). Conclusions: Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers, and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.

At present, all countries are accelerating the construction of a new type of power system based on renewable energy, and the random volatility and intermittency of new energy resources, and the low resistance and weak support of new energy power generation and grid-connected equipment exist objectively. In order to maintain the safe and stable operation of the power system, the demand for auxiliary services such as frequency regulation, peak regulation, voltage regulation, standby and black start is increasing. Therefore, with the increase of new energy penetration rate, it is necessary to explore the impact of the increase of new energy penetration rate on the cost of auxiliary services. Combined with the background that the foreign power market has been running for a long time, auxiliary service varieties are more abundant, and the new energy penetration rate of some countries or TSOs has reached a higher level, the author has conducted a study on the impact of the increase in the penetration rate of new energy on the cost of auxiliary services in foreign countries, explored the impact of the increase in the penetration rate of new energy on the cost of auxiliary services, and provided reference and guidance for the classification of auxiliary service products, the design of pricing mechanism and other key issues of the construction of the auxiliary service market in China. The study explores the impact of the increase of new energy penetration on the cost of auxiliary services, and provides reference and guidance for the division of auxiliary service products, design of pricing mechanism and other key issues of auxiliary service market in China.

This article considers the optimal bidding model of traditional thermal power generation companies’ electricity sales companies, taking into account transmission congestion, under the influence of new policies such as the renewable portfolio standard (RPS) and the renewable exchange certificate (REC). Firstly, the transaction cost of green certificates is included in the cost of electricity sales, and an optimization model is established with the goal of maximizing the profit of the electricity sales company; Secondly, the node electricity price method is used to manage transmission congestion, and an optimization model is established with the goal of minimizing the cost of transmission congestion; Finally, multi agent technology and dynamic game theory are used to solve the optimal bidding strategy of the electricity selling company.

Summary: The dysregulation of glutamine metabolism provides survival advantages for tumors by supplementing tricarboxylic acid cycle. Glutamate dehydrogenase 1 (GLUD1) is one of the key enzymes in glutamine catabolism. Here, we found that enhanced protein stability was the key factor for the upregulation of GLUD1 in lung adenocarcinoma. We discovered that GLUD1 showed a high protein expression in lung adenocarcinoma cells or tissues. We elucidated that STIP1 homology and U-box-containing protein 1 (STUB1) was the key E3 ligase responsible for ubiquitin-mediated proteasomal degradation of GLUD1. We further showed that lysine 503 (K503) was the main ubiquitination site of GLUD1, inhibiting the ubiquitination at this site promoted the proliferation and tumor growth of lung adenocarcinoma cells. Taken together, this study clarifies the molecular mechanism of GLUD1 in maintaining protein homeostasis in lung adenocarcinoma, which provides a theoretical basis for the development of anti-cancer drugs targeting GLUD1.

IntroductionThe application of technology supported by cyber infrastructure has emerged as a critical factor influencing city management. This study aims to investigate whether the development of cyber infrastructure can enhance cities’ confidence in responding to potential epidemic threats in the context of COVID-19.MethodsChina serves as a good example for both COVID-19 management and smart city construction. We take advantage of a special time point, the 2022 Chinese New Year, to observe cities’ precautionary epidemic policies. We utilize choice models and data from 188 Chinese cities to examine the impact of internet coverage on the degree of policy relaxation.ResultsWe found that cities with higher internet coverage tend to adopt looser policies. In the benchmark regression, for every 1 percentage point increase in internet coverage, the likelihood of implementing loose measures increases by 0.9 percentage points. This result remains robust across different classifications of policies. We also addressed potential endogeneity issues by using the instrumental variables method.DiscussionOur study indicates that effective management of epidemics in the modern era requires not only the utilization of traditional medical resources but also the incorporation of new city features, such as information technology infrastructure.

A new gas sensor system with fast response and ultra-high sensitivity has been developed based on a combination of frequency modulation spectroscopy (FMS) and cavity ring-down spectroscopy (CRDS). The system consisted of two distributed feedback laser diodes (DFB-LDs) emitting at frequencies 6251.761 cm-1 (Laser-1) and 6257.762 cm-1 (Laser-2), respectively. A portion of Laser-1’s output was used by a frequency modulation spectroscopy technique to lock its frequency precisely at a CO2 absorption peak, while the rest of its output was coupled to an optical ring-down cavity, together with the Laser-2 output. The Laser-2 operated at a non-absorbing frequency for real-time correction of any baseline ring-down time drift caused by environmental changes (e.g., temperature, pressure). Laser frequency stabilization achieved a 5-fold improvement in CRDS detection sensitivity. This new system was able to make measurements at a data rate of 9 Hz. Based on Allan deviation analysis, the absorbance detection limit of the system was 4.4 × 10−11 cm-1 at an optimum averaging time of ∼5 s, whereas the time-normalized sensitivity at 1 s was 7.3 × 10−11 cm-1/Hz1/2. Measurements of atmospheric CO2 mole fraction were conducted and demonstrated its good performance and reliability. This sensor will be particularly suitable for making drift-free measurements over long periods, in the fields of environmental and industrial gas sensing.

Constructed wetlands are commonly utilized to treat industrial wastewater due to their effectiveness, affordability, and environmental benefits. Many phosphorus chemical enterprises in the middle Yangtze River basin are facing high pollution load challenges and efforts are needed to improve removal efficiency of pollutants. This work was the first to use constructed wetlands for phosphorus chemical industry tailwater (PCITW) treatment. The new hybrid constructed wetlands (CWs) proposed were the aeration horizontal subsurface flow constructed wetland (AHSCW) and the integrated vertical flow constructed wetland (IVCW), which were constructed on a pilot scale. Here, the effectiveness of pollutant removal along hybrid CWs, wetland plant growth, and root-associated microbial community responses to the PCITW were investigated. The results showed that there was spatial variation in removal of carbon, nitrogen, and phosphorus in the hybrid CWs, and that the AHSCW and the IVCW played synergistic roles in the removal of pollutants. Compared with influent, the toxic effect of effluent to embryos of a rare minnow (Gobiocypris rarus) was alleviated. Exposure to the effluent resulted in no malformation or death for embryos. Plants and microorganisms in the wetland system of the phosphate chemical tailwater were then compared with the control system of municipal tailwater. Plants in the former system had lower root density, and higher average root diameter, root shoot ratio, specific root length, and specific surface area. Plant roots also had decreased NH4+ uptake ability but increased Ca2+ uptake to adapt to the high load and complex pollution stress. Unlike the control system, stochastic mechanisms had a more important role than deterministic processes in shaping the microbial community assembly associated with the PCITW. Meanwhile, analysis of microbial network-level topological characteristics demonstrated substantial reduction in network interactions complexity and microbiome stability in the treatment system. Findings from this study suggest wetlands will be helpful for efficient purification of phosphorus chemical industry wastewater in the Yangtze River basin.

[Purpose/Significance] Research on the demand and supply analysis of agricultural literature resources is of great significance to the collection construction of agricultural libraries, especially under the current new situation. The demand analysis of academic resources of agricultural science has always been a difficult task for agricultural special libraries because it covers a wide range of disciplines and involves the multiple cross and integrated applications of various disciplines with agriculture science. This paper innovates the methods of demand and supply analysis based on multi-level information organization and fine-grained data analysis, which would discover both the systematic demands and accurate demands of agricultural researchers, and help to adapt to the changes of agricultural science research paradigm. [Method/Process] This study took the Chinese Academy of Agricultural Sciences (CAAS) as an example, collecting its published foreign language journals and the corresponding cited references, as well as its usage data of foreign language electronic journals databases. Then this paper used the methods of citation analysis, subject organization, etc. to analyze the institutional demand characteristics that include literature language, document type, publication years, disciplines distribution, covered subjects and the utilized database of foreign-language periodical resources. The full-text supply rate of foreign-language electronic journals has been calculated to evaluate the satisfaction and the ability of supplying collection resources. The literature comprehensive utilization index has also been calculated to reflect the literature utilization capacity of CAAS's affiliated institutes by the methods of correlation analysis and multiple correlation coefficient weighting. [Results/Conclusions] The results show that the demands of foreign-language journals of CAAS involve not only classical agricultural disciplines but also some emerging and interdisciplinary fields, and there are big gaps in the level of literature supply and utilization among its affiliated institutes. The construction of literature resource supply system of CAAS should strengthen the demand analysis, enrich the subscription mode of full-text resources, and expand the non-full-text resources. As for the agricultural special libraries, the demand and supply analysis of agricultural science literature resources should follow the development trends of agricultural disciplines, taking into account the systematic and prospective demands, and carry out accurate, thematic and knowledge-based demand analysis in the relevant subject areas. Users can also be encouraged to participate in library collection construction, and diversified demand feedback channels should be provided for them. At the same time, resource construction quality and service efficiency evaluation should also be brought to the forefront.

In the 1840s F. M. Dostoevsky became famous in literary circles thanks to his story Poor Folk, but was widely criticized by the Slavophiles, namely by the Aksakov brothers for his creative approach and political ideology. In the 1860s heated disputes between Vremenya and Den’ confirmed Dostoevsky’s ideological disagreements with the Slavophiles. In the 1880s, as the author of the article shows, begins a convergence of Dostoevsky’s position, his artistic ideas and the views of the Aksakov brothers, which is especially noticeable in Dostoevsky’s speech at the Pushkin holiday. The article comprehends the main ideological differences and points of contact between pochvennichestvo and Slavophilism, traces the difficult relationship between Dostoevsky and the Aksakov brothers, which lasted more than 40 years. Numerous disagreements in the beliefs of these contemporaries concerned the issue of creative style, the purpose of literature and ideological currents. Dostoevsky believed in Slavophile thought, but was more progressive; he developed and deepened the ideals of fundamentalism in the second half of the 19th century.

Objectives Chronic kidney disease (CKD) is a serious health problem that is associated with several systemic changes, including protein energy wasting (PEW). However, the exact mechanism of PEW in CKD remains unclear. As one of the important intestinal flora metabolites and uremic toxins, trimethylamine-N-oxide (TMAO) is involved in CKD-associated mortality, which might play a role in the development of PEW in CKD patients especially in patients on maintenance hemodialysis (MHD). However, this possibility has not been investigated.Methods PEW was diagnosed in a group of CKD patients on MHD according to the criteria of the International Society of Renal Nutrition and Metabolism. Serum TMAO concentration was assessed by high-performance liquid chromatography and mass spectrometry. The association between TMAO concentration and PEW was assessed using linear regression and logistic analysis after adjustment for confounding factors, including basic characteristics, comorbidities, and laboratory findings.Results The circulating TMAO level was higher in the MHD patients than in control (healthy) individuals (5653.76 ± 2853.51 vs. 254.92 ± 197.88 ng/mL, p

As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good in vitro cellular uptake, the NPs-ALN also inhibited tumor growth both in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis.

Abstract Background Insulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice. Methods Glucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100 mg kg−1 d−1, p.o.) or vehicle for 4 weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4 weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Results Curcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota. Conclusions The effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.

Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products (AGEs)-induced neuronal cell apoptosis; however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A (SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase (V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification. Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial–lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy.

Objective: A rapid method for determination of bongkrekic acid in Auricularia auricular was developed using QuEChERS in combination with UHPLC-MS/MS. Methods： In this study, Several important experimental parameters, including type of extraction solvent, extraction time, adsorbent type and adsorbent dosage were effectively optimized using spiked samples. The sample were shaken with methanol containing 1% ammonia water, and then carried out by the C18 adsorbent purification. Results： The bongkrekic acid was determined within 4 minutes by negative ion multiple reaction monitoring mode analysis and external standard method. The linear range was 0.05~10.00 ng/mL （r＞0.998 3）. The limit of detection （LOD） was 2 μg/kg, respectively. The average recovery rate at different levels（low, medium and high） the intra-batch （n=6） was 74.4%~91.6%, the inter-batch （n=3） were 74.9%~89.4% with a RSD ranging from 3.3%~9.2%. Conclusion： The developed method shows simple, rapid, excellent recovery and stable repeatability, and the limit of detection lower than the existing detection standards. It is suitable for the effective detection of bongkrekic acid in Auricularia auricular samples.

AIM: To characterize peripheral refraction and its relationship with myopia development in a selected group of male teenage Chinese students. METHODS: This 2-year prospective cohort study randomly enrolled 85 non-myopic boys (age, 14-16y) from the Experimental Class of Air Force in China. Cycloplegic peripheral refraction was examined at 0°, ±10°, and ±20° along the horizontal visual field in the right eye at the baseline and 2-year follow-up. RESULTS: The incidence of myopia at the 2-year follow-up was 15.29% (13/85). The baseline central refraction (CR) and peripheral refraction at ±10° were significantly lower in students who developed myopia than in those who did not (P0.05). At the 2-year follow-up, the RPR at ±10° and 20° nasal was significantly more hyperopic in the myopic group than in the non-myopic group. Multiple linear regression analysis indicated that the change in CR was significantly correlated with the changes in RPR at 20° nasal, 10° nasal, and 20° temporal. Multivariate Logistic regression analysis indicated that the baseline CR [odds ratio (OR): 0.092, 95% confidence interval (CI): 0.012-0.688, P=0.020] and the baseline RPR at 10° nasal (OR: 0.182, 95%CI: 0.042-0.799, P=0.024) were significantly correlated with incident myopia (Omnibus test, χ2=10.20, P=0.006). CONCLUSION: CR change is significantly correlated with changes in RPR, and students who develop myopia have more relative peripheral hyperopia. More baseline CR and relative peripheral hyperopia at 10° nasal are protective of myopia onset.

With the improvement in people’s living standards, the development and application of smart textiles are receiving increasing attention. In this study, a carbon nanosurface was successfully coated with a SiO2 layer to form C@SiO2 nanomaterials, which improved the dispersion of carbon nanomaterials in an aqueous solution and enhanced the absorption of light by the carbon nanoparticles. C@SiO2 nanoparticles were coupled on the surface of silk fabric with the silane coupling agent KH570 to form C@SiO2 nanosilk fabric. The silk fabric that was subjected to such surface modification was endowed with a special photothermal function. The results obtained with scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and infrared spectroscopy (FTIR) showed that C@SiO2 nanoparticles were successfully modified on the surface of the silk fabric. In addition, under the irradiation of near-infrared light with a power of 20 W and a wavelength of 808 nm, the C@SiO2 nanosilk fabric experienced rapid warming from 23 °C to 60 °C within 30 s. After subjecting the functional fabric to hundreds of photothermal experiments and multiple washes, the photothermal efficiency remained largely unchanged and proved to be durable and stable. In addition, the thermogravimetric (TG) analysis results showed that the C@SiO2 nanoparticles contributed to the thermal stability of the silk fabric. The UV transmittance results indicated that C@SiO2 nanofabric is UV-resistant. The silk modification method developed in this study is low-cost, efficient, and environmentally friendly. It has some prospects for future applications in the textile industry.

In recent years, pea aphids have become major pests of alfalfa. Our previous study found that “Gannong 5” is a highly aphid-resistant alfalfa variety and that “Lie Renhe” is a susceptible one. The average field susceptibility index of “Gannong 5” was 31.31, and the average field susceptibility index of “Lie Renhe” was 80.34. The uptake and balance of amino acids in insects are usually dependent on amino acid transporters. RT-qPCR was used to detect the relative expression levels of seven amino acid transporter differential genes in the different instar pea aphids fed on resistant and susceptible alfalfa varieties after 24 h, and two key genes were selected. When pea aphids fed on “Gannong 5”, the expression of ACYPI004320 was significantly higher than that in pea aphids fed on “Lie Renhe”; however, the expression of ACYPI000536 was significantly lower than that in pea aphids fed on “Lie Renhe”. Afterward, the RNA interference with pea aphid ACYPI000536 and ACYPI004320 genes was performed using a plant-mediated method, and gene function was verified via liquid chromatography–mass spectrometry and pea aphid sensitivity to aphid-resistant and susceptible alfalfa varieties. The results showed that the down-regulation of the ACYPI000536 gene expression led to an increase in the histidine and lysine contents in pea aphids, which, in turn, led to an increase in mortality when pea aphids fed on the susceptible variety “Lie Renhe”. The down-regulation of the ACYPI004320 gene expression led to an increase in phenylalanine content in pea aphids, which, in turn, led to a decrease in mortality when pea aphids fed on the resistant variety “Gannong 5”.

Abstract Aim MATRICS Consensus Cognitive Battery was developed by the National Institute of Mental Health to establish acceptance criteria for measuring cognitive changes in schizophrenia and can be used to assess cognitive functions in other psychiatric disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to explore the changes in multiple cognitive functions in patients with mild cognitive impairment and mild Alzheimer's disease. Methods We administered the Japanese version of MATRICS Consensus Cognitive Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS Consensus Cognitive Battery domain scores were converted to t‐scores using sample means and standard deviations and were compared for significant performance differences among healthy control, MCI, and mild Alzheimer's disease groups. Results Compared with healthy controls, patients with MCI and mild Alzheimer's disease demonstrated the same degree of impairment to processing speed, verbal learning, and visual learning. Reasoning and problem‐solving showed significant impairments only in mild Alzheimer's disease. Verbal and visual abilities in working memory showed different performances in the MCI and mild Alzheimer's disease groups, with the Alzheimer's disease group demonstrating significantly more deficits in these domains. No significant difference was found among the groups in attention/vigilance and social cognition. Conclusions The Japanese version of MATRICS Consensus Cognitive Battery can be used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI, and mild dementia in clinical practice.

Extracellular vesicles (EVs) are complex biological nanoparticles endogenously secreted by all eukaryotic cells. EVs carry a specific molecular cargo of proteins, lipids, and nucleic acids derived from cells of origin and play a significant role in the physiology and pathology of cells, organs, and organisms. Upon release, they may be found in different body fluids that can be easily accessed via noninvasive methodologies. Due to the unique information encoded in their molecular cargo, they may reflect the state of the parent cell and therefore EVs are recognized as a rich source of biomarkers for early diagnostics involving liquid biopsy. However, body fluids contain a mixture of EVs released by different types of healthy and diseased cells, making the detection of the EVs of interest very challenging. Recent research efforts have been focused on the detection and characterization of diagnostically relevant subpopulations of EVs, with emphasis on label-free methods that simplify sample preparation and are free of interfering signals. Therefore, in this paper, we review the recent progress of the label-free optical methods employed for the detection, counting, and morphological and chemical characterization of EVs. We will first briefly discuss the biology and functions of EVs, and then introduce different optical label-free techniques for rapid, precise, and nondestructive characterization of EVs such as nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy, surface plasmon resonance spectroscopy, Raman spectroscopy, and SERS spectroscopy. In the end, we will discuss their applications in the detection of neurodegenerative diseases and cancer and provide an outlook on the future impact and challenges of these technologies to the field of liquid biopsy via EVs.

Abstract The prevalence and clinical relevance of pathogenic germline variants in MMR genes have not been investigated in large series of breast cancers. In this study, we screened the germline variants in MMR genes in 8085 consecutive Chinese breast cancer patients, and investigated the MMR/PD-L1 protein expression and tumor mutation burden (TMB) of breast tumors from MMR variant carriers. We found that 15 of 8085 patients (0.19%) carried a pathogenic germline variant in MMR genes. Compared with non-carriers, MMR variant carriers might have worse recurrence-free survival (unadjusted hazard ratios [HR] = 2.70, 95% CI: 1.12–6.49, P = 0.027) and distant recurrence-free survival (unadjusted HR = 3.24, 95% CI: 1.45–7.22, P = 0.004). More importantly, some of the breast cancers from MMR carriers displayed MMR protein loss (5/13), TMB-high (2/10), and PD-L1 positive expression (9/13). This study showed that MMR variant carriers were rare in breast cancer. They might have worse survival and part of them might benefit from immunotherapy.

Biostimulants play an important role in promoting crop growth and development and improving fruit yield, but their influence on fruit quality in horticulture plants is still unclear. In this study, four types of biostimulants, Ainuo (AN), Aigefu (AG), Weiguo (WG), and Guanwu Shuang (GS) were applied to the fruit surface of ‘Yinhongli’ plum at 60 and 75 days after anthesis to investigate their effect on carbohydrates and biosynthesis of anthocyanins, and also analyze the relationship between sugar and anthocyanin accumulation during fruit color change to ripening. Results showed that all biostimulant treatments significantly improved fruit appearance quality, and increased single fruit weight and TSS/TA. Cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside, are the most important anthocyanins in the red skin of the ‘Yinhongli’ plum, and no anthocyanin was detected in the green skin. In addition, WG and GS treatments significantly increased the expression of structural genes involved in anthocyanin biosynthesis compared with the control, especially chalcone synthase (CHS) and flavonoid 3-O-glucosyltransferase (UFGT) at 95-105 d after anthesis, leading to anthocyanin accumulation 10 days earlier than the control. Correlation analysis showed that there was a significant correlation between total sugar and anthocyanin content during fruit coloring and ripening.