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Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I’s effects on brain aging, Alzheimer’s disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms of neurodegeneration. Understanding the intricate role of IFN-I and its associated pathways in the CNS not only advances our comprehension of brain health and disease but also presents opportunities for developing interventions to modify the process of neurodegeneration and prevent age-related cognitive decline.

RNA sequencing (RNA-seq) technology has become one of the standard tools for studying biological mechanisms at the transcriptome level. Advances in RNA-seq technology have led to the development of numerous publicly available tools for RNA-seq data analysis. Most of these tools target linear genome sequences despite the necessity of studying organisms with circular genome sequences. For example, studying the infection mechanisms of viroids which comprise 246–401 nucleotides circular RNAs and target plants may prevent tremendous economic and agricultural damage. Unfortunately, using the available tools to construct workflows for the analysis of circular genome sequences is difficult, especially for non-bioinformaticians. To overcome this limitation, we present CircSeqAlignTk, an easy-to-use and richly documented R package. CircSeqAlignTk offers both command line and graphical user interfaces for end-to-end RNA-seq data analysis, spanning alignment to the visualisation of circular genome sequences, via a series of functions. Moreover, it includes a feature to generate synthetic sequencing data that mirrors real RNA-seq data from biological experiments. CircSeqAlignTk not only provides an easy-to-use analysis interface for novice users but also allows developers to evaluate the performance of alignment tools and new workflows.

Abstract As one of the most widespread components in marine sediments, calcium carbonate (CaCO3) plays a crucial role in the global carbon cycle and climate changes. To efficiently semi‐quantify the CaCO3 concentration, a more effective, non‐destructive, economic, and accurate technique is required. Diffuse reflectance spectroscopy (DRS) has been widely used for the detection and quantification of minerals but has been less studied for CaCO3. This study synthesized a series of samples with well‐determined content of CaCO3 to analyze the visible and near‐infrared DRS characteristics. Results show that the intensity of the second derivative of Kubelka‐Munk (K‐M) remission functions of the DRS spectra at 2,340 nm (I2340) is linearly correlated with the CaCO3 content. Then, the new proxy I2340 was applied for marine sediments from the Pacific Ocean with known CaCO3 concentrations determined previously by chemical methods, and the robustness of the I2340 as the proxy for CaCO3 concentration was attested.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Effective industrial policies need to be implemented, particularly aligning with environmental protection goals to drive the high-quality growth of China’s economy in the new era. Setting up national high-tech zones falls under the purview of both regional and industrial policies. Using panel data from 163 prefecture-level cities in China from 2007 to 2019, this paper empirically analyzes the impact of national high-tech zones on the level of urban green innovation and its underlying mechanisms. It utilizes the national high-tech zones as a quasi-natural experiment and employs a double machine learning model. The study findings reveal that the policy for national high-tech zones greatly enhances urban green innovation. This conclusion remains consistent even after adjusting the measurement method, empirical samples, and controlling for other policy interferences. The findings from the heterogeneity analysis reveal that the impact of the national high-tech zone policy on green innovation exhibits significant regional heterogeneity, with a particularly significant effect in the central and western regions. Among cities, there is a notable push for green innovation levels in second-tier, third-tier, and fourth-tier cities. The moderating effect results indicate that, at the current stage of development, transportation infrastructure primarily exerts a negative moderating effect on how the national high-tech zone policy impacts the level of urban green innovation. This research provides robust empirical evidence for informing the optimization of the industrial policy of China and the establishment of a future ecological civilization system.

To explore the feature of cancer cells and tumor subclones, we analyzed 101,065 single-cell transcriptomes from 12 colorectal cancer (CRC) patients and 92 single cell genomes from one of these patients. We found cancer cells, endothelial cells and stromal cells in tumor tissue expressed much more genes and had stronger cell-cell interactions than their counterparts in normal tissue. We identified copy number variations (CNVs) in each cancer cell and found correlation between gene copy number and expression level in cancer cells at single cell resolution. Analysis of tumor subclones inferred by CNVs showed accumulation of mutations in each tumor subclone along lineage trajectories. We found differentially expressed genes (DEGs) between tumor subclones had two populations: DEGCNV and DEGreg. DEGCNV, showing high CNV-expression correlation and whose expression differences depend on the differences of CNV level, enriched in housekeeping genes and cell adhesion associated genes. DEGreg, showing low CNV-expression correlation and mainly in low CNV variation regions and regions without CNVs, enriched in cytokine signaling genes. Furthermore, cell-cell communication analyses showed that DEGCNV tends to involve in cell-cell contact while DEGreg tends to involve in secreted signaling, which further support that DEGCNV and DEGreg are two regulatorily and functionally distinct categories.

The COVID-19 pandemic significantly disrupted global healthcare systems. The impacts of SARS-CoV-2 infection on urticaria and its management are unknown. This study aimed to collect information about patients with urticaria infected with SARS-CoV-2 and to investigate the impact of SARS-CoV-2 infection on urticaria severity, course, and treatment to better support recovery. This was a questionnaire-based study of patients with urticaria infected with SARS-CoV-2. Changes in urticaria severity (measured with the urticaria activity score (UAS)), course, and treatment were assessed before, during, and after SARS-CoV-2 infection. The mean (±SD) UAS scores were 5.17 ± 1.67, 4.23 ± 1.98, and 4.37 ± 1.93 before, during, and after SARS-CoV-2 infection, respectively (F = 8.839, p < 0.01). The median (IQR) wheal score was 0.464 (0.464, 0.763), 0.464 (0.138, 0.763), and 0.464 (0.138, 0.763) before, during, and after infection, respectively (Kruskal–Wallis H-test, H = 12.230, p = 0.02). The median (IQR) pruritus score was 0.695 (0.395, 0.695), 0.394 (0.123, 0.695), and 0.394 (0.123, 0.695) before, during, and after infection, respectively (Kruskal–Wallis H-test, H = 21.001, p < 0.01). Within the limitations of a questionnaire study, urticaria appears to improve during SARS-CoV-2 infection and worsens slightly after recovery, and the frequency of Western medicine use increases.

The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1−/− mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6−/− mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1−/− cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Abstract Because of the limited effectiveness of prevailing phylogenetic methods when applied to highly divergent protein sequences, the phylogenetic analysis problem remains challenging. Here, we propose a sequence-based evolutionary distance algorithm termed sequence distance (SD), which innovatively incorporates site-to-site correlation within protein sequences into the distance estimation. In protein superfamilies, SD can effectively distinguish evolutionary relationships both within and between protein families, producing phylogenetic trees that closely align with those based on structural information, even with sequence identity less than 20%. SD is highly correlated with the similarity of the protein structure, and can calculate evolutionary distances for thousands of protein pairs within seconds using a single CPU, which is significantly faster than most protein structure prediction methods that demand high computational resources and long run times. The development of SD will significantly advance phylogenetics, providing researchers with a more accurate and reliable tool for exploring evolutionary relationships.

Abstract. Background:. The effect of arteriosclerotic intracranial arterial vessel wall enhancement (IAVWE) on downstream collateral flow found in vessel wall imaging (VWI) is not clear. Regardless of the mechanism underlying IAVWE on VWI, damage to the patient's nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow. The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow. Methods:. The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery (MCA) M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset. The patients were divided into 4 groups according to IAVWE and the stenosis ratio (Group 1, n = 17; Group 2, n = 19; Group 3, n = 13; Group 4, n = 14), and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling (3D-pCASL) and RAPID software. The National Institutes of Health Stroke Scale (NIHSS) scores of the patients were also recorded. Two-factor multivariate analysis of variance using Pillai's trace was used as the main statistical method. Results:. No statistically significant difference was found in baseline demographic characteristics among the groups. IAVWE, but not the stenosis ratio, had a statistically significant significance on the late-arriving retrograde flow proportion (LARFP), hypoperfusion intensity ratio (HIR), and NIHSS scores (F = 20.941, P

Abstract Background Antiretroviral therapy (ART) improved the prognosis of people living with human immunodeficiency virus (HIV) (PLWH). Life-long treatment is required in PLWH and is accompanied by various metabolic abnormalities in the disease course. Data about the epidemiology and the dynamic changes of dyslipidemia in PLWH receiving antiretroviral therapy were scarce in Asian countries. This study aimed to explore the risk factors of dyslipidemia and analyze the longitudinal changes of dyslipidemia among Chinese PLWH receiving HAART. Methods We conducted a longitudinal analysis of PLWH enrolled in two large multicenter clinical trials across China, and outpatients followed at the clinic of Peking Union Medical College Hospital. Demographic data and clinical parameters were collected. The risk factors and longitudinal changes in lipid profiles associated with HIV-1 infection were analyzed. The definition of dyslipidemia was made based on the National Cholesterol Education Program, Adult Treatment Panel (NCEP-ATP) III guidelines. Results A total of 1542 PLWH were included. The median follow-up was 6 years. At baseline, the concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.1 ± 0.91 mmol/L, 1.2 (interquartile ranges [IQR] 0.85–1.75) mmol/L, 1.1 ± 0.37 and 2.4 ± 0.76 mmol/L, respectively. The rate of hypercholesterolemia, hyperglyceridemia, high LDL-C, and low HDL-C were 10.18%, 26.39%, 9.08%, and 44.94%, respectively. The overall prevalence of dyslipidemia was 69.3%, which raised to 84.3% after antiretroviral therapy, substantially higher. CD4/CD8 ratio 105 copies/mL were risk factors associated with any subtype of dyslipidemia. A negative correlation between CD8+CD38+ percentage and HDL-C concentration was found. The regimens including efavirenz (EFV) and tenofovir (TDF) showed better lipid profiles. Longitudinal analysis revealed that both the level and the percentage of abnormal TG and HDL-C occurred drastic change in the first 6 months after ART initiation (from 4.07 to 4.41, from 1.11 to 1.28mmol/L, from 26.39 to 31.1% and from 44.94 to 29.5%, respectively). Conclusions The prevalence of dyslipidemia is high in PLWH and increases after ART, mainly represented as high TG and low HDL-C and associated with advanced stage of HIV-1 infection. The greatest changes in lipids occurred in the early stage after initiating ART therapy. The results suggest that dyslipidemia should be monitored and managed when starting ART.

Abstract Background Although there is a robust relationship among social trauma, optimism, and depression, the inner mechanism of this correlation remains unclear and need to be further explored. The mainly purpose of the current study was to investigate the relationship between social trauma, optimism, and depression among college students in China. More specifically, examined the moderating role of the optimism between social trauma and depression in Chinese college students. Methods A sample of 464 Chinese college students (54.7% female, Mage=19.29) from three universities were selected by the convenient sampling, and the Social Trauma Questionnaire (STQ), the Optimism Questionnaire (OPQ), and the Self-Rating Depression (SDS) were completed by these Chinese undergraduates. The descriptive statistics, Pearson correlations, and hierarchical regression analysis were used to examine the results. Results (1) The social trauma was positively associated with depression, whereas the optimism was negatively associated with social trauma, and depression; (2) The social trauma had a significant correlation with depression, and the optimism could moderate the relationship between social trauma and depression. More specifically, the further study showed that there was a significant positive relation between social trauma and depression under the low optimism level, however, there was a non-significant relation between social trauma and depression under the high optimism level. Conclusion The optimism is the protective mechanism of college students’ mental health (e.g., depression), it could weaken the trauma that associated with social trauma among college students.

Y2O3–ZrO2 ceramic powder has emerged as a vital structural and functional material in ceramic applications owing to its remarkable performance including wear resistance, temperature resistance, and corrosion resistance. Agglomeration during the drying process is the other key issue that needs to be resolved, which improving the quality of zirconia powder becomes crucial in reducing industrial expenses. This study focuses on investigating the influence of modern microwave heating technology on the drying kinetics of Y2O3–ZrO2 ceramic powder. The experimental results revealed that the average drying rate of Y2O3–ZrO2 ceramic powder increased with sample water content, microwave heating power, and sample mass. Four kinetic fitting models, namely Page, Wang and Singh, Quadratic Model, and Modified Page, were employed to analyze the experimental data for Y2O3–ZrO2 ceramic powder with a mass of 20 g, initial water content of 7.5%, and the microwave heating power is 480 W. Among these models, the Modified Page model demonstrated the best fit and effectively described the drying kinetics of Y2O3–ZrO2 ceramic powder. The Modified Page model successfully captured the kinetics across varying masses, microwave heating powers, and initial water content. FT-IR spectroscopy was employed to describe the material before and after microwave drying. The results exhibited a significant reduction in water molecule content in the Y2O3–ZrO2 ceramic powder after microwave drying, thus confirming the high efficiency and rapidity of the microwave drying procedure. This research provides comprehensive experimental data and offers a theoretical foundation for the industrial application of microwave-enhanced drying of Y2O3–ZrO2 ceramic powder.

The electron beam cold hearth melting (EBCHM) process is one of the key processes for titanium alloy production. However, EBCHM is prone to cause elemental volatilization and segregation during the melting of aluminum-containing titanium alloys such as Ti-6wt%Al-4wt%V. To gain deeper insights into the physical and chemical phenomena occurring during the EBCHM process, this paper establishes melting process models for the Ti-6wt%Al-4wt%V titanium alloy in a crystallizer with multiple overflow inlets. It examines the evolution of melt pool morphology, flow dynamics, heat transfer, and mass transfer during the casting process. The results indicate that the design of multi-overflow inlets can effectively suppress the longitudinal development of impact pits within the melt pool, thereby preventing the formation of solidification defects such as leaks in the melt. Concurrently, the diversion effect of multi-overflow inlets significantly enhances the elemental homogeneity within the melt pool. At a casting speed of 20 mm/min and a casting temperature of 2273 K, compared to a single overflow inlet, the design with three overflow inlets can reduce the depth of thermal impact pits within the crystallizer by 132 mm and decrease the maximum concentration difference in the Al element within the crystallizer by 0.933 wt.%. The aforementioned simulation results provide a theoretical basis for the control of metallurgical and solidification defects in large-scale titanium alloy ingots.

The South China Block, a region renowned for its extensive granite distribution and rich metal deposits, serves as a natural laboratory for the study of granite-related mineralization. This research focuses on the Tongtianmiao granite pluton, which is located at the intersection of the Qin-Hang and Nanling metallogenic belts and has been confirmed as a significant lithium mineral resource. Despite its discovery and ongoing development, the lithium-rich Tongtianmiao pluton has been understudied, particularly concerning its petrogenesis, which has only recently come to the forefront of scientific inquiry. By integrating an array of petrogeochemical data with geochronological studies derived from zircon and monazite dating, this study provides insights into the magmatic processes related to lithium enrichment in the Tongtianmiao granites. The Tongtianmiao granites are classified as A-type granites characterized by high SiO2 contents (69.18–78.20 wt.%, average = 74.08 wt.%), K2O + Na2O contents (4.59–8.34 wt.%, average = 6.86 wt.%), A/CNK > 1.2, and low concentrations of Ca, Mg, and Fe. These granites are enriched in alkali metals such as Li, Rb, and Cs but are significantly depleted in Ba, Sr, and Eu. They show no significant fractionation of light or heavy rare-earth elements but present characteristic tetrad effects. A finding of this study is the identification of multiple ages from in situ zircon U–Pb dating, which implies a prolonged history of magmatic activity. However, given the high uranium content in zircons, which could render U–Pb ages unreliable, emphasis is placed on the monazite U–Pb ages. These ages cluster at approximately 172.1 ± 1.1 Ma and 167.9 ± 1.6 Ma, indicating a Middle Jurassic period of granite formation. This timing correlates with the retreat of the Pacific subduction plate and the associated NE-trending extensional fault activity, which likely provided favorable conditions for lithium enrichment. The study concluded that the Tongtianmiao granites were formed through partial melting of crustal materials and subsequent underplating by mantle-derived materials, and were contaminated by strata materials. This process resulted in the formation of highly differentiated granite through magmatic differentiation and external forces. These findings have significant implications for understanding the petrogenesis of lithium-rich granites and are expected to inform future exploration endeavors in the Tongtianmiao pluton.

This paper investigates the role of chaotic analysis and deep learning models in combustion instability predictions. To detect the precursors of impending thermoacoustic instability (TAI) in a swirled combustor with various fuel injection strategies, a data-driven framework is proposed in this study. Based on chaotic analysis, a recurrence matrix derived from combustion system is used in deep learning models, which are able to detect precursors of TAI. More specifically, the ResNet-18 network model is trained to predict the proximity of unstable operation conditions when the combustion system is still stable. The proposed framework achieved state-of-the-art 91.06% accuracy in prediction performance. The framework has potential for practical applications to avoid an unstable operation domain in active combustion control systems and, thus, can offer on-line information on the margin of the combustion instability.

The ultra-low friction observed between water and carbon nanotubes has been extensively reported recently. In this study, we delve into the factors influencing the liquid–solid friction, including surface properties such as surface wettability and roughness of carbon nanotubes, as well as the driving forces involving temperature gradient and pressure drop. Utilizing non-equilibrium molecular dynamics simulations on carbon nanotube models with a diameter of ~1 nm, we observe a significant increase in water flux within a specific range of wettability, independent of roughness. This range is expected to shift to smaller values with increased pressure drop and temperature gradient. Both the mechanical transport coefficient and the thermo-osmosis coefficient exhibit a negative correlation with wettability, and roughness further decreases these coefficients. Through this work, we provide insights into the effects of surface properties on fluid transport through nanopores, contributing valuable information for the optimization of high-performance membrane processes.

Abstract Introduction Since hematopoietic stem cell transplant (HSCT) is an important therapy for malignant and non-malignant pediatric diseases, improving transplant-related mortality remains a challenge. Currently, rituximab, a monoclonal antibody of anti-CD20, is widely used for several post-HSCT complications. However, few studies have focused on the application of rituximab before HSCT. Methods We conducted a retrospective case–control study from January 2019 to July 2021 to determine this effect in a single center. Forty-eight patients were included in the rituximab group, with a one-to-one ratio matched to the control group. Results Both the occurrence rate and cumulative incidence rate of Epstein–Barr virus (EBV) infection were significantly lower in the rituximab group than in the without-rituximab group (10.4% vs. 33.3%, p = 0.014 and 12.2% vs. 39.3% p = 0.0026, respectively). Furthermore, without the application of rituximab was identified as a risk factor for post-HSCT EBV infection via both univariate [hazard ratio (HR) = 4.17, 95%CI (1.52–11.43), p = 0.005] and multivariate analyses [HR = 4.65, 95%CI (1.66–13.0), p = 0.003]. Although the overall survival (OS) probability of the rituximab group was comparable to the without-rituximab group, a markedly improved OS of the rituximab group was found in the malignant disease subgroup (78.9% vs. 42.1%, p = 0.032). The outcomes of graft-versus-host disease, neutrophil and platelet engraftment, other viral infections, and the reconstitution of lymphocytes showed no significant differences between the two groups. Conclusions The administration of rituximab before HSCT may prevent EBV infection following HSCT.

Abstract Background The ability of lung cancer screening to manage pulmonary nodules was limited because of the high false‐positive rate in the current mainstream screening method, low‐dose computed tomography (LDCT). We aimed to reduce overdiagnosis in Chinese population. Methods Lung cancer risk prediction models were constructed using data from a population‐based cohort in China. Independent clinical data from two programs performed in Beijing and Shandong, respectively, were used as the external validation set. Multivariable logistic regression models were used to estimate the probability of lung cancer incidence in the whole population and in smokers and nonsmokers. Results In our cohort, 1,016,740 participants were enrolled between 2013 and 2018. Of 79,581 who received LDCT screening, 5165 participants with suspected pulmonary nodules were allocated into the training set, of which, 149 lung cancer cases were diagnosed. In the validation set, 1815 patients were included, and 800 developed lung cancer. The ages of patients and radiologic factors of nodules (calcification, density, mean diameter, edge, and pleural involvement) were included in our model. The area under the curve (AUC) values of the model were 0.868 (95% CI: 0.839–0.894) in the training set and 0.751 (95% CI: 0.727–0.774) in the validation set. The sensitivity and specificity were 70.5% and 70.9%, respectively, which could reduce the 68.8% false‐positive rate in simulated LDCT screening. There was no substantial difference between smokers' and nonsmokers' prediction models. Conclusion Our models could facilitate the diagnosis of suspected pulmonary nodules, effectively reducing the false‐positive rate of LDCT for lung cancer screening.

Fe–Mn–Al–C austenitic steels have promising prospects for lightweight applications, due to their low density, excellent strength, and ductility. But the specific strength ratio of these alloys are still low as compared to other alloys. Herein, an orthogonal rolling (OR) process was used to improve the mechanical strength of a Fe–28Mn–8Al–1C low-density steel. The effect of this deformation method on the microstructural evolution and mechanical properties was studied by means of microscopy techniques, e.g. optic, scanning and transmission electron microscope, electron backscattered diffraction, X-ray diffraction, micro hardness and tensile test measurements. Microstructural characterization results show that OR significantly promotes the activation of multiple slip systems within grains in the material. The development of more uniform deformation microstructure, compared with that that after unidirectional cold rolling to the same strain was mainly due the improvement of the uniformity of strain distribution by rolling deformation in multiple directions. It resulted in an average 84.5 nm sized ultrafine grain structures after 8-pass OR. The tensile and yield strengths were significantly increased to 1813 MPa and 1798 MPa, respectively. Despite of the still-exiting strength-ductility trade-off, a much higher elongation at tensile failure of 9.6% was achieved, compared to only 5.2% of unidirectional cold rolled material. This superior strength and ductility combination was likely promoted by the increased dislocation density and deformation substructures in forms of dislocation cells, and deformation twins induced by OR.

Abstract Current progress in two-dimensional (2D) materials explorations leads to constant specie enrichments of possible advanced materials down to two dimensions. The metal chalcogenide-based 2D materials are promising grounds where many adjacent territories are waiting to be explored. Here, a stable monolayer Ni3TeO6 (NTO) structure was computationally predicted and its stacked 2D nanosheets experimentally synthesized. Theoretical design undergoes featuring coordination of metalloid chalcogen, slicing the bulk structure, geometrical optimizations and stability study. The predicted layered NTO structure is realized in nanometer-thick nanosheets via a one-pot shape-controlled hydrothermal synthesis. Compared to the bulk, the 2D NTO own a lowered bandgap energy, more sensitive wavelength selectivity and an emerging photocatalytic hydrogen evolution ability under visible light. Beside a new 2D NTO with the optoelectrical and photocatalytic merits, its existing polar space group, structural specification, and design route are hoped to benefit 2D semiconductor innovations both in species enrichment and future applications.

Abstract This paper focuses on designing a power allocation strategy for a fuel cell ship. The performance of the fuel cell varies during operation, so a power allocation strategy considering fuel cell performance differences is proposed, which consists of two layers. In the first layer, the maximum power and maximum efficiency of each fuel cell system (FCS) are updated in real-time with an online parameter identification model, which is composed of the fuel cell semi-empirical model and adaptive Kalman filter. The second layer takes the state of charge of the battery energy storage system, the maximum power, and the maximum efficiency as inputs for power allocation. Compared with the equal allocation strategy and daisy chain strategy, the total hydrogen consumption reduces by 5.3% and 15.1% and the total output power of the FCS with poor performance reduces by 14.1% and 15.7%. The results show that the proposed method can improve the efficiency of the ship power system and reduce the operational burden of the FCS with poor performance.

Let $ q $ be an even prime power and let $ \mathbb{F}_{q} $ be the finite field of $ q $ elements. Let $ f $ be a nonzero polynomial over $ \mathbb{F}_{q^2} $ of the form $ f = a_{1}x_{1}^{m_{1}}+\dots+a_{s}x_{s}^{m_{s}}+y_{1}y_{2}+\dots+y_{n-1}y_{n}+y_{n-2t-1}^{2}+\dots +y_{n-3}^2+y_{n-1}^{2}$ $+b_{t}y_{n-2t}^{2}+ $ $ \dots +b_{1}y_{n-2}^{2}+b_{0}y_{n}^{2} $, where $ a_{i}, b_j\in \mathbb{F}_{q^{2}}^{*}, $ $ m_i\ne 1, $ $ (m_{i}, m_{k}) = 1, $ $ i\ne k, $ $ m_{i}|(q+1), $ $ m_{i}\in \mathbb{Z}^{+}, $ $ 2|n $, $ n > 2 $, $ 0\leq t\leq \frac{n}{2}-2 $, $ {\mathrm{Tr}}_{\mathbb{F}_{q^2}/\mathbb{F}_{2}}(b_{j}) = 1 $ for $ i, k = 1, \dots, s $ and $ j = 0, 1, \dots, t $. For each $ b \in \mathbb{F}_{q^2} $, let $ N_{q^2}(f = b) $ denote the number of $ \mathbb{F}_{q^2} $-rational points on the affine hypersurface $ f = b $. In this paper, we obtain the formula of $ N_{q^2}(f = b) $ by using the Jacobi sums, Gauss sums and the results of quadratic form in finite fields.

Abstract The fuel cell system (FCS) is commonly combined with an energy storage system (ESS) for enhancing the performance of the ship. Consequently, the battery ESS size and power allocation strategy are critical for the hybrid energy system. This paper focuses on designing a method to solve these two problems. First, a battery degradation model is employed to assess the ESS lifetime. Subsequently, the sizing problem and the optimal power allocation are integrated into a cost‐minimization problem, which is solved by a double‐loop optimization approach. The inside loop utilizes the battery degradation model to calculate ESS lifetime. In the outside loop, a power allocation strategy based on the hybrid Particle Swarm Optimization algorithm and Gray Wolf Optimization algorithm is presented. Finally, the power allocation strategy is extended to real‐time implementation by the equivalent consumption minimization strategy (ECMS) and an improved ECMS is proposed to make the FCS operates near the maximal efficiency point. Compared with ECMS, the operating cost reduces by 0.26%. The result indicates that the proposed method can optimize the ESS size efficiently, and the power allocation strategy can assure the stable operation of the fuel cell ship.

Abstract Background Pneumonia is the leading cause of death among children under five, and kill almost two million children each year. Quercetin, a flavonoid polyphenolic compound, exerts many beneficial biological activities, including anti‐inflammatory functions. Our study aimed to investigate the possibility of quercetin as a therapeutic agent for pneumonia and its role in the inflammatory response induced by lipopolysaccharide (LPS). Methods LPS induced human alveolar epithelial cell A549 as a lung inflammation model in vitro. The effects of quercetin on the production of cytokines and the expression of related‐proteins were detected by Enzyme‐Linked ImmunoSorbent Assay and Western Blot, respectively. Cell Counting Kit‐8 assay was used to detect cell viability. flow cytometry was used to measure cell apoptosis. NO levels were also analyzed through NO kit. Results Our results found that quercetin attenuated the release of IL‐1β, IL‐6, PGE2, and nitrite in LPS‐induced A549 cells. In addition, quercetin inhibits cell apoptosis and relieves ROS generation in LPS‐induced A549 cells. Quercetin also inhibits LPS‐induced NF‐κB activation. They have upregulated the expression of nuclear factor erythroid 2 (Nrf2) and HO‐1. Conclusion In conclusion, these results suggested that quercetin attenuates LPS‐induced inflammation in A549 by activating the Nrf2 signaling pathway.

Platinum is known as the best catalyst for the hydrogen evolution reaction (HER) but the scarcity and high cost of Pt limit its widespread applicability. Herein, the role of the underlying substrate on the HER activity of dispersed Pt atoms is uncovered. A direct current magnetron sputtering technique is utilized to deposit transition metal (TM) thin films of W, Ti, and Ta as underlying substrates for extremely low loading of Pt (

Emerging evidence has indicated that the alterations in gut microbiota and metabolites are associated with cognitive performance. However, whether these associations imply a causal relationship remains to be definitively established. Here, we conducted two-sample mendelian randomization (MR) studies to explore the causal effects of gut microbiota and metabolites on cognitive performance, using large-scale genome-wide association studies (GWASs). We identified seven positive causalities between host genetic-driven gut microbiota and cognitive performance, including Class Clostridia (p = 0.0002), Order Clostridiales (p = 8.12E-05), Family Rhodospirillaceae (p = 0.042) and Ruminococcustorquesgroup (p = 0.030), Dialister (p = 0.027), Paraprevotella (p = 0.037) and RuminococcaceaeUCG003 (p = 0.007) at the genus level. Additionally, a total of four higher abundance of gut microbiota traits were identified to be negatively related to cognitive performance, including genus Blautia (p = 0.013), LachnospiraceaeFCS020group (p = 0.035), LachnospiraceaeNK4A136group (p = 0.034) and Roseburia (p = 0.00016). In terms of plasma metabolites, we discovered eight positive and six negative relationships between genetic liability in metabolites and cognitive performance (all p

Coupled nuclear and electronic dynamics within a molecule are key to understanding a broad range of fundamental physical and chemical processes. Although probing the coupled vibrational and electronic dynamics was demonstrated, it has so far been challenging to observe the coupling interactions between the rotational and electronic degrees of freedom. Here, we report the first observation of Coriolis coupling, a coupling interaction between nuclear rotational angular momentum and electronic axial angular momentum, during laser-induced molecular fragmentation by tracing the electronic structure of a dissociating [Formula: see text] molecule. We observe that the electron density changes its shape from that of a molecular σ orbital to a nearly isotropic shape as the internuclear distance goes up to ∼20 Å, which results from the transition between nearly degenerate electronic states associated with different rotational angular momenta. Our experiment demonstrates that the breaking of a chemical bond does not occur suddenly during molecular dissociation. Instead, it lasts for a long time of several hundred femtoseconds due to the Coriolis coupling interaction. Our experiment can be extended to complicated molecules, holding the potential of revealing yet unobserved electron–nuclear coupling interactions during ultrafast processes.

Introduction: Low estimated glomerular filtration rate (eGFR) is associated with an increased risk of arterial stiffness in participants with kidney damage. It is uncertain whether this association is due to eGFR itself or is mediated by the eGFR-associated increases in fasting blood glucose (FBG). Method: The cross-sectional study included 865 Japanese participants with decreased kidney function, whose eGFR was less than 90mL/min/1.73m², were recruited from individuals who received medical healthcare. The mediating variable was FBG, with eGFR as the independent variable and brachial-ankle pulse wave velocity (baPWV) as the dependent variable. A mediation analysis was used to evaluate the mediating effect of FBG on the association between eGFR and arterial stiffness. Results: The mean age of the participants was 51.69 ± 9.25 years old, with 65.90% individuals being male. The mean values for FBG, eGFR and baPWV were 5.46 ± 0.79 mmol/L, 68.83 ± 10.05 mL/min/1.73m², and 1423.50 ± 247.78 cm/s, respectively. The mediation analysis revealed that eGFR had a significant direct effect on baPWV (β=-25.68 95%CI (-46.42,-7.45), and that FBG played a partial mediating role in the indirect effect of eGFR on baPWV (β=-3.54 95%CI (-11.88,-0.079). Mediation analysis showed that 12.10% of the effect of eGFR on risk of arterial stiffness was mediated through FBG. Conclusion: The study indicated that there is a mediating relationship between eGFR and FBG in people with decreased kidney function, which is associated with the risk of arterial stiffness. Therefore, the importance of FBG as a mediator should be acknowledged and taken into consideration.

ObjectiveThis study aims to analyze the efficacy of anti-syphilis treatment and the impact of syphilis events on HIV virology and immunology in HIV/syphilis co-infected patients on long-term antiretroviral therapy (ART) and to investigate the incidence and factors of syphilis recurrence/re-infection/serofast state. The insights derived from this investigation can potentially guide strategies for preventing and managing syphilis and AIDS.MethodsA retrospective case–control study was conducted at the AIDS clinic of Peking Union Medical College Hospital from January 2003 to December 2022. The study involved 86 HIV/syphilis co-infected patients and 86 HIV mono-infected patients matched based on age, baseline CD4 + T cell counts, and viral load. We examined the clinical characteristics of HIV/syphilis co-infected patients, evaluated the efficacy of anti-syphilis treatment, and analyzed the dynamic changes in HIV virology and immunology. The Generalized Estimating Equations (GEE) model investigated the factors associated with HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state.ResultsSyphilis serofast state was observed in 11.6% (10/86) of HIV/syphilis co-infected patients after treatment, and 33.7% (29/86) had syphilis recurrence or re-infection. The overall effectiveness of syphilis treatment stood at 76.8% (63/82). Notably, the effectiveness of syphilis treatment displayed a significant correlation with baseline syphilis titers exceeding 1:128 (p = 0.003). Over the 10-year follow-up period on ART, the HLA-DR + CD8+/CD8 + % levels in the HIV/syphilis co-infected group were markedly higher than those in the HIV mono-infected group (p 0.05). GEE analysis model revealed that elevated HLA-DR + CD8+/CD8 + % levels were associated with HIV/syphilis co-infection (OR = 1.026, 95% CI = 1.007–1.046; p = 0.007) and syphilis recurrence/reinfection/serofast state (OR = 1.036, 95% CI = 1.008–1.065; p = 0.012).ConclusionWhile HIV/syphilis co-infected patients typically receive adequate treatment, the incidence of syphilis recurrence and reinfection remain notably elevated. A heightened HLA-DR + CD8+/CD8+ % is a notable risk factor for HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state. Therefore, it is advisable to reinforce health education efforts and ensure regular follow-ups for people living with HIV undergoing ART to monitor syphilis infection or increased risk of syphilis infection.

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence in situ hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC.

Neoadjuvant chemoimmunotherapy has demonstrated significant benefit for resectable non-small-cell lung cancer (NSCLC) excluding known EGFR/ALK genetic alterations. Recent evidence has shown that neoadjuvant chemoimmunotherapy could be clinically valuable in resectable localized driver gene-mutant NSCLC, though the data still lack robust support, especially for rare oncogenic mutations. Here, we report a patient with stage IIIA lung adenocarcinoma with a RET fusion gene and high expression of PD-L1 who underwent neoadjuvant chemoimmunotherapy and successfully attained a pathologic complete response. The patient has survived for 12 months with no recurrence or metastases after surgery. Our case suggests that this treatment strategy may be an alternative therapeutic option for resectable RET fusion-positive NSCLC patients.

As global demand for ecological resources continues to surpass ecosystem capacity, predicting future changes in ecological supply, consumption, and carrying capacity is crucial for informed decision-making regarding sustainable land use and ecological security. This study forecasts ecological carrying states in Nepal, a representative region in the southern Himalayan foothills, from 2020 to 2030. We employ three alternative scenarios from the Shared Socioeconomic Pathway and Representative Concentration Pathway (SSP-RCP): SSP2-RCP4.5 (BAU), SSP1-RCP2.6 (TSS) and SSP5-RCP8.5 (SSS). Our findings indicate a continuous rise in ecological consumption, particularly in densely populated tropical areas such as the hilly region (HR) and Terai region (TR). Under the BAU and SSS scenarios, ecological supply decreases rapidly in these regions. Alarmingly, over one-third of Nepal's districts, mainly in central and eastern HR and TR, are projected to experience overloaded ecological carrying states by 2030. Climate change sensitivity and escalating consumption due to improved living standards and population growth pose significant challenges for these regions to reverse ecological deficits. This study offers a scientific foundation for reconciling the conflict between ecological protection and societal demands, facilitating the preservation, restoration, and sustainable use of terrestrial ecosystems while striving to achieve the Sustainable Development Goals by 2030.

There are abundant coal resources in the permafrost regions of the Qinghai-Tibet Plateau. Open-pit mining is the primary method for coal extraction due to its simple technology and cost-effectiveness. However, the mining process can lead to degradation in permafrost regions. Underground coal mining has been adopted as an option to minimize the impact on the permafrost environment. However, underground coal mining in permafrost regions, along with ventilation, can disrupt the thermal equilibrium of frozen rocks around the shaft, leading to changes in the permafrost table and the seasonal thawed layer around the shaft. Therefore, it is necessary to predict the temperature field of frozen rocks under mine ventilation. Some researchers focus on the temperature of frozen rocks in respect to constant airflow temperature. In fact, the airflow temperature in the shaft varies related to shaft depth, ground temperature, ventilation amount, and ventilation time. In this study, we utilize field data to construct two numerical models for predicting the temperature regime of frozen rocks. The first model, using the finite difference method, describes airflow temperature in the shaft within permafrost regions, accounting for variations in shaft depth, ground temperature, initial rock temperature, ventilation time, and ventilation amount. A fitting equation is then determined as a third boundary condition. The second model employs the finite element method to solve the heat transfer equation with phase change. The results indicate that the maximum thaw depth of frozen rocks around the shaft of Jiangcang coal mine ranged from 3.25 to 5.3 m at various shaft depths. This maximum thaw depth occurs on September 15th and is correlated with ventilation time, stabilizing after three years. Natural ventilation offers protection to frozen rocks around the shaft, and these results can serve as references for designing support systems in underground mining within permafrost regions.

Abstract Background Endothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in PD are poorly defined. Methods We combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD. This was combined with EC‐selective blockade of glycolysis by genetic or pharmacological inhibition of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) in vivo and in vitro. We also investigated the association between peritoneal EC glycolysis and microvascular alterations in human peritoneal samples from patients with end‐stage kidney disease (ESKD). Results In a mouse model of PD, peritoneal ECs had a hyperglycolytic metabolism that shunts intermediates into nucleotide synthesis. Hyperglycolytic mouse peritoneal ECs displayed a unique active phenotype with increased proliferation, permeability and inflammation. The active phenotype of mouse peritoneal ECs can be recapitulated in human umbilical venous ECs and primary human peritoneal ECs by vascular endothelial growth factor that was released from high glucose‐treated mesothelial cells. Importantly, reduction of peritoneal EC glycolysis, via endothelial deficiency of the glycolytic activator PFKFB3, inhibited PD fluid‐induced increases in peritoneal capillary density, vascular permeability and monocyte extravasation, thereby protecting the peritoneum from the development of structural and functional damages. Mechanistically, endothelial PFKFB3 deficiency induced the protective effects in part by inhibiting cell proliferation, VE‐cadherin endocytosis and monocyte‐adhesion molecule expression. Pharmacological PFKFB3 blockade induced a similar therapeutic benefit in this PD model. Human peritoneal tissue from patients with ESKD also demonstrated evidence of increased EC PFKFB3 expression associated with microvascular alterations and peritoneal dysfunction. Conclusions These findings reveal a critical role of glycolysis in ECs in mediating the deterioration of peritoneal function and suggest that strategies targeting glycolysis in peritoneal ECs may be of therapeutic benefit for patients undergoing PD.

Background Idiopathic membranous nephropathy is widely recognized as an autoimmune kidney disease that is accompanied by the discovery of several autoantibodies, and the antibody subclass in the circulation of patients with iMN is mainly IgG. However, the direct pathogenic effect of the containing anti-PLA2R IgG antibody on podocytes is not clear.Method A protein G affinity chromatography column was used to purify serum IgG antibodies. Containing anti-PLA2R IgG antibodies from iMN patients and IgG from healthy controls were also obtained. Based on the established in vitro podocyte culture system, purified IgG antibodies from the two groups were used to stimulate podocytes, and the expression of essential podocyte proteins (podocin), the levels of inflammatory cytokines in the cell supernatant, cytoskeletal disorders, and podocyte apoptosis were analyzed.Results Compared with that in the normal IgG group, the expression of podocin and podocin mRNA was reduced (p = 0.016 and p = 0.005, respectively), the fluorescence intensity of podocin on the surface of podocytes was reduced, the cytoskeleton of podocytes was disordered and reorganized, and the ratio of podocyte apoptosis was increased in the iMN group (p = 0.008).Conclusion The containing anti-PLA2R IgG antibody might have a direct damaging effect on podocytes in idiopathic membranous nephropathy.

AbstractThe selection and planning of the location of emergency shelters have a crucial impact on the safety of residents and cities. In this paper, based on multivariate open geographic data, the Gaussian two-step floating catchment area method, K-means clustering, and particle swarm optimization algorithm methods are utilized to carry out a spatial accessibility analysis and location optimization of emergency shelters in Deyang City, Sichuan Province, China. The study shows that: (1) Deyang City’s emergency shelters are higher than the government’s relevant standard requirements in terms of major indicators such as single building area, total area and per capita shelter area. (2) The spatial distribution of emergency shelters in the study area is uneven and unreasonable, with accessibility from the urban center outwards, exhibiting a “high-low” distribution pattern. (3) The study suggests that 10 new emergency shelters can reduce the number of accessible blind areas by 43.31%. The study recommends that the assessment and construction of emergency shelter facilities in rural areas in China and globally should be emphasized. Reliable recommendations for improvement of emergency shelter planning in Deyang city are provided in the study results.

ABSTRACTAs a hallmark of COVID-19 progression, lymphopenia alongside its subtle immune disturbance has been widely reported, but yet to be thoroughly elucidated. Aiming at exploring clinical immune biomarkers with accessibility in the current and acute omicron epidemic abrupted in China post-control era, we design a real-world prospective observation cohort in Peking Union Medical College Hospital to describe immunological, haematological profiles inducing lymphocyte subsets related to SARS-CoV-2 infection. In this COVID-19 cohort, we enrolled 17 mild/moderate (M/M), 24 severe (S) and 25 critical (C) patients. The dynamics of lymphocytes of COVID-19 demonstrated that the sharp decline of NK, CD8+, and CD4+ T cell counts was the main contributor to lymphopenia in the S/C group, compared to the M/M group. Expressions of activation marker CD38 and proliferation marker Ki-67 both in CD8+ T and NK cells were significantly higher in all COVID-19 patients than that in healthy donors, independent of disease severity. The subsequent analysis showed in contrast to the M/M group, NK and CD8+ T cell counts remained low-level after therapy in the S/C group. CD38 and Ki-67 expressions in NK and CD8+ T cells still stay at a high level, despite active treatment. Targeting relatively elderly patients with SARS-CoV-2 infection, severe COVID-19 features the unreversible reduction of NK and CD8+ T cells with persistent activation and proliferation, which assist clinicians in early recognizing and saving severe or critical COVID-19 patients. Given that immunophenotype, the new immunotherapy improving NK and CD8+ T lymphocyte antiviral efficiency should be considered.

AbstractBackground Diabetic kidney disease (DKD) is a leading cause of kidney failure worldwide. Anxiety has been associated with disease progression in non-diabetes patients. We aimed to examine the prospective association between anxiety and progression of DKD in type 2 diabetes.Methods We conducted a prospective cohort study of 2040 participants with type 2 diabetes at the Diabetes Center of Shanghai General Hospital between May 2017 and June 2020. Anxiety disorders at baseline were diagnosed by a structured clinical interview based on the 10th Revision of International Classification of Disease (ICD). Progression of DKD was identified as the transition from one urinary albumin excretion rate (AER) stage to the next or the development of kidney failure during the follow-up period.Results At baseline, 403 (19.8%) had a diagnosis of anxiety disorders, of whom 107 (26.6%) also received a depression diagnosis. During a median follow-up time of 3.2 years, deterioration of the kidney status occurred in 340 (16.7%) individuals. After adjustment for potential confounders including depression or an anxiety × depression interaction term, anxiety disorders were independently related to an increased risk of progression of DKD (HR 1.539, 95% CI 1.130–2.095, p = 0.006; HR 1.536, 95% CI 1.111–2.122, p = 0.009, respectively).Conclusions Anxiety disorders at baseline, independent of possible confounders, were associated with the progression of DKD in type 2 diabetes. Whether therapeutic interventions for anxiety reduce the risk needs to be investigated.

Abstract Chronic kidney disease (CKD) and heart failure (HF) are highly prevalent, aggravate each other, and account for substantial mortality. However, the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain limited. Here, we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ (SFO) and thereby to paraventricular nucleus (PVN) and rostral ventrolateral medulla that modulates sympathetic outflow. This kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each model. Interruption of the pathway by kidney deafferentation, selective deletion of angiotensin II type 1a receptor (AT1a) in SFO, or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and HF. Thus, kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both organs. These results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease conditions. This suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.

[Introduction] In order to improve the problem of traditional proportion integration differentiation (PID) controllers overly relying on the mathematical model of the controlled object in the temperature control in hydrogen production by water electrolysis, this paper studies the application of fuzzy internal model control in the temperature control in hydrogen production by water electrolysis, and provides the design process of the fuzzy internal model controller. [Method] Firstly, the importance of temperature in the process of hydrogen production by water electrolysis was analyzed, and some temperature control strategies commonly used in hydrogen production by water electrolysis and their advantages and disadvantages were listed. Then, internal model control theory and fuzzy theory were introduced, and a design method for a fuzzy internal model temperature controller, which was used to achieve precise temperature control in hydrogen production by water electrolysis, was proposed based on these two theories. Finally, simulation verification experiments were conducted. [Result] The results show that the fuzzy internal model control method used in this paper has better control quality in response speed, anti-interference, and robustness compared to the PID control method, solving the problem of traditional PID controller algorithms overly relying on the mathematical model of the controlled object. [Conclusion] The control algorithms used in this paper are correct and effective, and can be applied to the temperature control in hydrogen production by water electrolysis.

Al2O3–ZrO2 composite ceramic is a significant structural material and functional material, and the preparation of high-quality Al2O3–ZrO2 powder is a key step to meeting practical application requirements. The major factor affecting the quality of Al2O3–ZrO2 powder is the drying effect. This paper uses modern microwave drying technology to dry Al2O3–ZrO2 powder. The result was indicative that the average drying rate increases with initial moisture content, initial mass, and microwave heating power. Four dynamic models were applied to fit the empirical data of Al2O3–ZrO2 powder under different pretreatment conditions, the Modified Page model can precisely delineate the Al2O3–ZrO2 microwave drying procedure. To evaluate the changes in samples before and post-drying, the specimens were characterized by Fourier transform infrared spectroscopy. These results demonstrate that microwaves can accelerate the drying of Al2O3–ZrO2 and improve its dispersion. Fick's second law calculates the effective diffusion coefficient. When the initial moisture content of Al2O3–ZrO2 was 5.6%, the microwave heating power is 560 W, and the initial quality is 15 g, the effective diffusion coefficient of Al2O3–ZrO2 is 0.006361 m2/s. Based on the relevance of the microwave power and activating energy, the activating energy of microwave drying Al2O3–ZrO2 was calculated, which is −34.80 g/W. This paper provides basic study data and theory instructions for microwave drying technology in drying Al2O3–ZrO2 even the drying process in green metallurgy.

In cold regions, the thermal effect of accumulated water on underlying permafrost and permafrost subgrade remains a significant hazard causing engineering risks. Water depth of accumulated water may be an important influence factor of permafrost thermal stability, but there is lack of qualitative and quantitative research about that. In this study, equivalent thermal conductivity theory and solid heat transfer theory have been used to establish the calculation model for simulating heat transfer in water and soil. Thereafter, the accuracy and reliability of the calculation model are checked by monitored data and subsequently used to analyze the thermal erosion of water on underlying permafrost and permafrost under the embankment. These simulation results show that shallow water can protect permafrost and deeper water disrupts the thermal stability of underlying permafrost. The thermal effect extent of water is primarily determined by its depth, and the concept of critical depth and stable depth of accumulated water has been proposed. Moreover, the temperature field of permafrost under embankment can be changed by the slope toe water. In addition, the thermal effect range of the slope toe water is limited by the thermal influence radius, which increases with the depth of standing water. These findings provide support as well as a fundamental base for environmental issues arising from the accumulated water. These observations will, thus, also be valuable to further engineering environment studies in cold regions.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects about 2% of children. Due to the shortage of clinicians, there is an urgent demand for a convenient and effective tool based on regular videos to assess the symptom. Computer-aided technologies have become widely used in clinical diagnosis, simplifying the diagnosis process while saving time and standardizing the procedure. In this study, we proposed a computer vision-based motion trajectory detection approach assisted with machine learning techniques, facilitating an objective and effective way to extract participants’ movement features (MFs) to identify and evaluate children’s activity levels that correspond to clinicians’ professional ratings. The designed technique includes two key parts: (1) Extracting MFs of participants’ different body key points in various activities segmented from autism diagnostic observation schedule (ADOS) videos, and (2) Identifying the most relevant MFs through established correlations with existing data sets of participants’ activity level scores evaluated by clinicians. The research investigated two types of MFs, i.e., pixel distance (PD) and instantaneous pixel velocity (IPV), three participants’ body key points, i.e., neck, right wrist, and middle hip, and five activities, including Table-play, Birthday-party, Joint-attention, Balloon-play, and Bubble-play segmented from ADOS videos. Among different combinations, the high correlations with the activity level scores evaluated by the clinicians (greater than 0.6 with p

Abstract Assembly-line polyketide synthases (PKSs) are molecular factories that produce diverse metabolites with wide-ranging biological activities. PKSs usually work by constructing and modifying the polyketide backbone successively. Here, we present the cryo-EM structure of CalA3, a chain release PKS module without an ACP domain, and its structures with amidation or hydrolysis products. The domain organization reveals a unique “∞”-shaped dimeric architecture with five connected domains. The catalytic region tightly contacts the structural region, resulting in two stabilized chambers with nearly perfect symmetry while the N-terminal docking domain is flexible. The structures of the ketosynthase (KS) domain illustrate how the conserved key residues that canonically catalyze C–C bond formation can be tweaked to mediate C–N bond formation, revealing the engineering adaptability of assembly-line polyketide synthases for the production of novel pharmaceutical agents.