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Abstract Poverty alleviation remains an urgent issue in China’s rural areas, with health poverty being a critical dimension. This study analyzed the multidimensional health poverty status of 9,052 rural residents in Ningxia in 2019 and 7,910 in 2022, aiming to provide a reference for optimizing health poverty alleviation strategies. The A-F dual cutoff method was used to identify and measure multidimensional health poverty through dimensions such as health status, health service utilization capacity poverty, and health spending and security poverty. Logistic regression analysis was further applied to examine the influencing factors of multidimensional health poverty. The results indicate that when the k-value is set at 0.3, the incidence of multidimensional health poverty was 22.3% in 2019 and 7.7% in 2022. The corresponding multidimensional health poverty indices were 0.091 and 0.028, respectively. Furthermore, the level of multidimensional health poverty was higher among women than men. Chronic diseases were identified as a significant indicator of multidimensional health poverty. At the individual level, gender, age, education, government subsidies, family size, housing, and digital divide significantly effected health poverty. Although multidimensional health poverty has improved in rural northwest China, targeted measures remain essential, especially for rural women, individuals with chronic illnesses, and those facing challenges in accessing healthcare and digital connectivity. Sustainable multidimensional health poverty alleviation should prioritize remote rural areas, especially by enhancing healthcare resource utilization for rural women and individuals with chronic diseases. Additionally, increasing medical subsidies for marginalized groups is essential. Improving rural housing conditions, strengthening digital infrastructure, and raising digital health literacy are also critical steps.

Abstract The rapid emergence of large language model (LLM) technology presents promising opportunities to facilitate the development of synthetic reactions. In this work, we leveraged the power of GPT-4 to build an LLM-based reaction development framework (LLM-RDF) to handle fundamental tasks involved throughout the chemical synthesis development. LLM-RDF comprises six specialized LLM-based agents, including Literature Scouter, Experiment Designer, Hardware Executor, Spectrum Analyzer, Separation Instructor, and Result Interpreter, which are pre-prompted to accomplish the designated tasks. A web application with LLM-RDF as the backend was built to allow chemist users to interact with automated experimental platforms and analyze results via natural language, thus, eliminating the need for coding skills and ensuring accessibility for all chemists. We demonstrated the capabilities of LLM-RDF in guiding the end-to-end synthesis development process for the copper/TEMPO catalyzed aerobic alcohol oxidation to aldehyde reaction, including literature search and information extraction, substrate scope and condition screening, reaction kinetics study, reaction condition optimization, reaction scale-up and product purification. Furthermore, LLM-RDF’s broader applicability and versability was validated on various synthesis tasks of three distinct reactions (SNAr reaction, photoredox C-C cross-coupling reaction, and heterogeneous photoelectrochemical reaction).

Abstract Background Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare hereditary disorder caused by variants in PKHD1. Currently, aberrant splicing has been reported to play important roles in genetic disease. Our goal is to analyze intronic variants in PKHD1 at the mRNA level. Results The 12 candidate variants were introduced into the corresponding minigene and functionally assayed in HEK 293T and Hela cells. We identified 11 variants that induce splicing alterations, resulting in various consequences such as skipping of exons, intron retention and protein truncation. Conclusions This underlined the importance of mRNA-level assessment for genetic diagnostics in related genetic disorders.

Abstract Radiotherapy (RT), a common cancer treatment, unintentionally harms surrounding tissues, including the skin, and hinders wound healing years after treatment. This study aims to understand the mechanisms behind these late-onset adverse effects. We compare skin biopsies from previously irradiated (RT+) and non-irradiated (RT−) sites in breast cancer survivors who underwent RT years ago. Here we show that the RT+ skin has compromised healing capacity and fibroblast functions. Using ATAC-seq, we discover altered chromatin landscapes in RT+ fibroblasts, with THBS1 identified as a crucial epigenetically primed wound repair-related gene. This is further confirmed by single-cell RNA-sequencing and spatial transcriptomic analysis of human wounds. Notably, fibroblasts in both murine and human post-radiation wound models show heightened and sustained THBS1 expression, impairing fibroblast motility and contractility. Treatment with anti-THBS1 antibodies promotes ex vivo wound closure in RT+ skin from breast cancer survivors. Our findings suggest that fibroblasts retain a long-term radiation memory in the form of epigenetic changes. Targeting this maladaptive epigenetic memory could mitigate RT’s late-onset adverse effects, improving the quality of life for cancer survivors.

Abstract Background High-temperature fermentation technology is promising in improving fermentation speed and product quality, and thereby widely used in various fields such as food, pharmaceuticals, and biofuels. However, extreme temperature conditions can disrupt cell membrane structures and interfere with the functionality of biological macromolecules (e.g. proteins and RNA), exerting detrimental effects on cellular viability and fermentation capability. Results Herein, a microbial thermotolerance improvement strategy was developed based on adaptive laboratory evolution (ALE) for efficient high-temperature fermentation. Employing this strategy, we have successfully obtained Corynebacterium glutamicum strains with superior resistance to high temperatures. Specifically, the genome analysis indicated that the evolved strains harbored 13 missense genetic mutations and 3 same-sense genetic mutations compared to the non-evolved parent strain. Besides, reverse transcription quantitative PCR analysis (RT qPCR) of the hrcA-L119P mutant demonstrated that both groEL genes were upregulated under 42 °C, which enabled the construction of robust strains with improved heat tolerance. Furthermore, a significant increase in FAS-IA and FAS-IB expression of the fasR-L102F strain was proved to play a key role in protecting cells against heat stress. Conclusions This work systematically reveals the thermotolerance mechanisms of Corynebacterium glutamicum and opens a new avenue for revolutionizing the design of cell factories to boost fermentation efficiency.

Abstract Background Disulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear. Methods Firstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot. Results Although SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients. Conclusion This study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.

Abstract Background The multidimensional health poverty afflicting rural women of reproductive age bears profound implications for the sustainable development of families, societies, and healthy villages. Elucidating vulnerable groups at risk of multidimensional health poverty and delineating its determinants can inform refinements and implementation of health-poverty alleviation policies. Methods Based on the 2022 "Health Status and Health Service Utilization" survey data in rural Ningxia, China, this study analyzes the dimension of health status, capacity for health service utilization, health expenditure and security using the A-F dual-threshold method, logit model, and probit model. It comprehensively evaluates multidimensional health poverty and analyzes its determining factors among rural women of childbearing age. Results With k set at 0.3, the health multidimensional poverty index, incidence, and intensity among rural women of reproductive age were 0.021, 0.053, and 0.392, respectively. Chronic illness, capacity for free gynecological examination utilization, health examination utilization, and borrowing due to illness contributed significantly to multidimensional health poverty. Risk factors for multidimensional health poverty among rural women of childbearing age include age, unemployment, family size, and lack of sanitary toilets. Protective factors include being married, educational level, non-farm or student occupation, receiving government support, separate housing and kitchen, owning a television and computer. Conclusions Even with the elimination of absolute poverty, the multidimensional health poverty situation among rural women remains important from a gender perspective. It is recommended to strengthen economic assistance and health service support for these groups, improve the level of rural health services from a gender perspective, and enhance housing structure and sanitation toilet usage in rural areas. Efforts should be made to narrow the digital divide in rural areas and promote digital health education. Pre-interventions on multidimensional health poverty can provide new pathways for the development, empowerment, and well-being of rural women of childbearing age.

Abstract The cell transition from an inflammatory phase to a subsequent proliferative phase is crucial for wound healing, yet the driving mechanism remains unclear. By profiling lncRNA expression changes during human skin wound healing and screening lncRNA functions, we identify SNHG26 as a pivotal regulator in keratinocyte progenitors underpinning this phase transition. Snhg26-deficient mice exhibit impaired wound repair characterized by delayed re-epithelization accompanied by exacerbated inflammation. Single-cell transcriptome analysis combined with gain-of-function and loss-of-function of SNHG26 in vitro and ex vivo reveals its specific role in facilitating inflammatory-to-proliferative state transition of keratinocyte progenitors. A mechanistic study unravels that SNHG26 interacts with and relocates the transcription factor ILF2 from inflammatory genomic loci, such as JUN, IL6, IL8, and CCL20, to the genomic locus of LAMB3. Collectively, our findings suggest that lncRNAs play cardinal roles in expediting tissue repair and regeneration and may constitute an invaluable reservoir of therapeutic targets in reparative medicine.

Abstract Background Patients with extensive-stage small cell lung cancer (ES-SCLC) experience significant therapeutic challenges and limited survival rates. This study aimed to investigate the efficacy of combining immunotherapy (IT) with chemotherapy (CT) for treating ES-SCLC and to explore the synergistic effect between radiotherapy (RT) and IT. Methods This retrospective analysis examined patients with ES-SCLC who received treatment at three centers. Furthermore, propensity score-matched (PSM) analysis was conducted. The Kaplan‒Meier method and Cox proportional hazards regression were used to compare the survival outcomes. Results A total of 257 eligible patients with ES-SCLC were included in the analysis. Among all patients, the median overall survival (mOS) was 18.0 m in the chemoimmunotherapy (CT + IT) group and 15.7 m in the CT group (p = 0.208). The median real-world progression-free survival (mrwPFS) was 7.7 m and 6.8 m (p = 0.043) in the CT + IT and CT group, respectively. Moreover, the mOS was 22.0 m in the chemoradiotherapy (CT + RT) group and 13.6 m in the CT group (p

Different initial microstructures significantly influence the final microstructures and mechanical properties of the intercritically annealed quenching and partitioning steels. Previous studies have primarily focused on the mechanism for the inheritance of different initial microstructures into the final microstructures, which affects the phase fraction and mechanical properties. However, these studies have overlooked the existence of an inheritance window in the intercritical annealing process. In this study, we investigated the inheritance window and explored the impact of varying initial microstructures on the reverse transformation of austenite, final phase fraction, and mechanical properties. Our findings reveal that the varying initial microstructure exhibits minimal influence on the final microstructure and mechanical properties for short or long annealing times. However, for the intercritical annealing treatment for 60 s, the initial microstructure of martensite with more nucleation sites accelerated the austenite reverse transformation fraction, enhanced the reverse-transformed austenite content, increased the primary martensite content, and improved the yield strength. Conversely, the coil-cooled sample, with initial microstructures consisting of ferrite and pearlite without dissoluble Mn-rich cementites, reduced the austenite reverse transformation rate, decreased the reverse-transformed austenite content, enhanced the ferrite and RA content, and improved ductility.

Abstract Peripheral nerve injury (PNI) occurs due to damage of peripheral nerves, with healthcare professionals playing significant roles in PNI rehabilitation. This study aimed to explore the knowledge, attitudes, and practices (KAP) towards PNI rehabilitation among healthcare professionals. This cross-sectional study was conducted on June 2023 in China and healthcare professionals were enrolled. A total of 611 valid questionnaires were collected, with 62.52% female respondents. Mean scores for KAP were 14.26 ± 2.044 (possible range: 0–19), 29.77 ± 3.622 (possible range: 7–35), and 41.55 ± 9.523 (possible range: 11–55), respectively. Multivariate logistic regression revealed positive associations of professional titles (OR = 1.743, 95% CI: 1.083–2.804), occupation (OR = 1.833, 95% CI: 1.151–2.919), and involvement in treatment or care of PNI patients (OR = 1.462, 95% CI: 1.024–2.088) with knowledge. Knowledge (OR = 1.155, 95% CI: 1.042–1.280), gender (OR = 2.140, 95% CI: 1.255–3.646), education (OR = 2.258, 95% CI: 1.131–4.507), and involvement in treatment or care of PNI patients (OR = 2.463, 95% CI: 1.460–4.155) were positively associated with attitude. Attitude (OR = 1.214, 95% CI: 1.148–1.283), bachelor's degree education (OR = 0.548, 95% CI: 0.326–0.919), master's degree or higher (OR = 0.545, 95% CI: 0.308–0.964), having rehabilitation training for PNI (OR = 2.485, 95% CI: 1.633–3.781), and involvement in treatment or care of PNI patients (OR = 2.093, 95% CI: 1.395–3.138) were independently associated with practice. Healthcare professionals exhibited moderate knowledge, positive attitudes, and moderate practices towards the PNI rehabilitation. Those involved in the treatment or care of PNI have significantly higher KAP. Targeted interventions were needed to enhance understanding and promote proactive engagement in clinical practice.

Abstract Aims/Introduction We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease’s degree. Materials and Methods We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)‐194 and thrombospondin‐1 (TSP‐1) messenger ribonucleic acid (mRNA) in the participants’ circulation were measured using a quantitative real‐time polymerase chain reaction. Results Circulating TSP‐1 mRNA (P = 0.024) and miR‐194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP‐1 mRNA (P = 0.040) and miR‐194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP‐1 mRNA expression increased with urinary microalbumin. However, miR‐194 declined in group B and increased in group C. Circulating TSP‐1 mRNA was positively correlated with cystatin‐c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR‐194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin‐c (β = 0.578; P = 0.021) and UmALB/Cr (β = 0.001; P = 0.009) as independent factors for TSP‐1 mRNA; UmALB/Cr (β = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP‐1 mRNA and miR194 were 0.756 (95% confidence interval 0.620–0.893; sensitivity 0.69 and specificity 0.71, P

Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.

Abstract Background Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. Results In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. Conclusions In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.

[Introduction] In order to improve heat exchange efficiency, the condensate pipelines, main water supply pipelines drain pipelines and partial extraction pipelines of nuclear power plants are all coated outside the pipelines. At present, the test methods of ferromagnetic pipelines are mainly conventional ultrasound and ultrasonic guided waves. These test methods are limited by the detection environment and preconditions, which increase the difficulty of test. In order to improve the test efficiency of pipelines with insulation layer, we shall enrich technical methods, shorten maintenance period and improve economic benefit of nuclear power plant. [Method] This paper mainly studied the feasibility and reliability of pulsed eddy current testing method under low frequency electromagnetic interference in nuclear power plant, and used the measured and calculated values of the induced voltage to establish the optimal parameter inversion problem. In combination with the coupling relationship between the parameters and based on the time-domain analytical solution of the pipeline pulsed eddy current field, the paper established the specific relationship between the measured value and the calculated value of the induced voltage, and established the optimization parameter inversion problem. In combination with the coupling relationship between the parameters, the paper proposed a pulsed eddy current detection method for in-service operation and maintenance of insulated pipes in nuclear power plants. [Result] Using the pulsed eddy current detection method for the relative wall thickness of ferromagnetic pipelines proposed in this paper, in-service sample pipelines of nuclear power plant are tested and the testing result is compared with conventional ultrasonic testing. The error of the two testing results is about 5%. [Conclusion] The testing results of impulse eddy current testing are reliable and it is suitable for non-destructive testing and evaluation of nuclear power plant ferromagnetic pipeline wall thickness corrosion thinning.

As a high-intensity, high-standard institutional mechanism in land supervision and management, the State Land Supervision System (SLSS) plays a crucial role in deterring land-related violations, enforcing farmland protection, ensuring national food security, and facilitating sustainable agricultural development. However, previous research has seldom examined how the SLSS contributes to the low-carbon transformation of agriculture (LCTA). This study treats China’s routine land inspections as a quasi-natural experiment, utilizing panel data from 283 prefecture-level and higher cities from 2005 to 2016 to empirically analyze whether and how the SLSS supports LCTA. The findings reveal that the SLSS significantly advances LCTA, with the low-carbon agricultural development level in inspected cities increasing by approximately 2.17%. The SLSS promotes LCTA primarily through enhancing agricultural technological progress and encouraging agricultural scale operations. Compared to major grain-producing regions, high-poverty areas, and regions under significant fiscal pressure, the SLSS more effectively fosters LCTA in non-grain-producing areas, regions with lower poverty rates, and areas facing less fiscal strain. Furthermore, the SLSS has a more pronounced effect on advancing low-carbon agricultural development in cities that already demonstrate higher levels of low-carbon progress. This study provides novel empirical evidence regarding the environmental impacts of SLSS in the agricultural sector, offering insights relevant to the pursuit of agricultural modernization.

Abstract Compressed ultrafast photography (CUP) can capture irreversible or difficult‐to‐repeat dynamic scenes at the imaging speed of more than one billion frames per second, which is obtained by compressive sensing‐based image reconstruction from a compressed 2D image through the discretization of detector pixels. However, an excessively high data compression ratio in CUP severely degrades the image reconstruction quality, thereby restricting its ability to observe ultrafast dynamic scenes with complex spatial structures. To address this issue, a discrete illumination‐based CUP (DI‐CUP) with high fidelity is reported. In DI‐CUP, the dynamic scenes are loaded into an ultrashort laser pulse train with controllable sub‐pulse number and time interval, thus the data compression ratio, as well as the overlap between adjacent frames, is greatly decreased and flexibly controlled through the discretization of dynamic scenes based on laser pulse train illumination, and high‐fidelity image reconstruction can be realized within the same observation time window. Furthermore, the superior performance of DI‐CUP is verified by observing femtosecond laser‐induced ablation dynamics and plasma channel evolution, which are hardly resolved in the spatial structures using conventional CUP. It is anticipated that DI‐CUP will be widely and dependably used in the real‐time observations of various ultrafast dynamics.

In this study, the dynamic process of a droplet moving with a substrate until blocked by air flow is investigated experimentally and theoretically. A sequence of experiments has been conducted to investigate the impacts of wetting properties, droplet volumes, air flow velocities, and droplet velocities. The substrate is driven by a linear motion motor to ensure the droplet moves at a certain velocity alongside the substrate. The air flow that is vertically injected from the nozzles toward the substrate is known as an impinging jet. After the air flow impacts the substrate, it will blow horizontally. When the direction of air flow is opposite to that of the droplet movement, a force will be exerted on the surface of the droplet. This action incurs the deformation of the droplet and the cessation of its movement, eventually resulting in an equilibrium state. The droplet shape and motion processes are recorded by a high-speed camera. A mathematical model considering the effect of droplet contact angle, droplet size, droplet moving velocity, and air flow velocity is established in the state of equilibrium. Correlation factors are used in the model for the drag coefficient and air average velocity acting on the droplet. It is found that the air flow rate required to stop the motion of the droplet increases with the droplet moving velocity and the droplet size but reduces with the increase in the static contact angle. The mathematical model, when equipped with suitable correlation factors, exhibits good agreement with experimental data and could potentially be utilized as a predictor of critical velocity for the cessation of the droplet motion.

BackgroundConstitution is a valuable part of traditional Chinese medicine theory; it is defined as the internal foundation for the occurrence, development, transformation and outcome of diseases, and has its characteristic gut microbiota. Previous study showed that deficiency constitution was related to lower Hb counts. However, no research has examined how alterations in the gut microbiome induced by deficiency constitution may increase the tendency for anemia.MethodsWe used a multiomics strategy to identify and quantify taxonomies and compounds found under deficient constitution individuals and further explore the possible pathological factors that affect red blood cell indices.Results① People with deficient constitution showed lower hemoglobin (Hb), more Firmicutes, less Bacteroidetes, and higher α diversity. ② We identified Escherichia coli, Clostridium bolteae, Ruminococcus gnavus, Streptococcus parasanguinis and Flavonifractor plautii as potential biomarkers of deficient constitution. ③ Slackia piriformis, Clostridium_sp_L2_50 and Bacteroides plebeius were enriched in balanced-constitution individuals, and Parabacteroides goldsteinii was the key bacterial marker of balanced constitution. ④ Flavonifractor plautii may be a protective factor against the tendency for anemia among deficient individuals. ⑤ Ruminococcus gnavus may be the shared microbe base of deficiency constitution-related the tendency for anemia. ⑥ The microorganism abundance of the anaerobic phenotype was lower in deficient constitution group. ⑦ Alterations in the microbiome of deficient-constitution individuals were associated with worse health status and a greater risk of anemia, involving intestinal barrier function, metabolism and immune responses, regulated by short-chain fatty acids and bile acid production.ConclusionThe composition of the gut microbiome was altered in people with deficient constitution, which may explain their poor health status and tendency toward anemia.

Background With the gradual increase of infertility in the world, among which male sperm problems are the main factor for infertility, more and more couples are using computer-assisted sperm analysis (CASA) to assist in the analysis and treatment of infertility. Meanwhile, the rapid development of deep learning (DL) has led to strong results in image classification tasks. However, the classification of sperm images has not been well studied in current deep learning methods, and the sperm images are often affected by noise in practical CASA applications. The purpose of this article is to investigate the anti-noise robustness of deep learning classification methods applied on sperm images.Methods The SVIA dataset is a publicly available large-scale sperm dataset containing three subsets. In this work, we used subset-C, which provides more than 125,000 independent images of sperms and impurities, including 121,401 sperm images and 4,479 impurity images. To investigate the anti-noise robustness of deep learning classification methods applied on sperm images, we conducted a comprehensive comparative study of sperm images using many convolutional neural network (CNN) and visual transformer (VT) deep learning methods to find the deep learning model with the most stable anti-noise robustness.Results This study proved that VT had strong robustness for the classification of tiny object (sperm and impurity) image datasets under some types of conventional noise and some adversarial attacks. In particular, under the influence of Poisson noise, accuracy changed from 91.45% to 91.08%, impurity precison changed from 92.7% to 91.3%, impurity recall changed from 88.8% to 89.5%, and impurity F1-score changed 90.7% to 90.4%. Meanwhile, sperm precision changed from 90.9% to 90.5%, sperm recall changed from 92.5% to 93.8%, and sperm F1-score changed from 92.1% to 90.4%.Conclusion Sperm image classification may be strongly affected by noise in current deep learning methods; the robustness with regard to noise of VT methods based on global information is greater than that of CNN methods based on local information, indicating that the robustness with regard to noise is reflected mainly in global information.

Abstract Point-scanning microscopy approaches are transforming super-resolution imaging. Despite achieving parallel high-speed imaging using multifocal techniques, efficient multicolor imaging methods with high-quality illumination are currently lacking. In this paper, we present for the first time Mechanical-scan-free multiColor Super-resolution Microscopy (MCoSM) with spot array illumination, which enables mechanical-scan-free super-resolution imaging with adjustable resolution and a good effective field-of-view based on spatial light modulators. Through 100–2,500 s super-resolution spot illumination with different effective fields of view for imaging, we demonstrate the adjustable capacity of MCoSM. MCoSM extends existing spectral imaging capabilities through a time-sharing process involving different color illumination with phase-shift scanning while retaining the spatial flexibility of super-resolution imaging with diffractive spot array illumination. To demonstrate the prospects of MCoSM, we perform four-color imaging of fluorescent beads at high resolution. MCoSM provides a versatile platform for studying molecular interactions in complex samples at the nanoscale level.

The refinement of bainitic ferrite laths is one of the most critical ways to improve the combination of strength and ductility. However, low-temperature bainitic transformations in the microstructural evolution of carbide-free bainite in high-carbon steels cause challenges for both the manufacture of coils and their application in car bodies. In this study, deformation-induced bainite refinement was proposed for refining bainite and retained austenite laths using a combination of ausforming and austempering in low-carbon low-alloy steel. The deformed austenite supplied more nucleation sites for bainitic transformation and suppressed the thickening of the bainitic ferrite laths by strengthening the surrounding untransformed austenite. A tensile strength of 1283 MPa and total elongation of 23.6% were obtained in the steel with an ausforming strain of 40% before austempering. The significant increase in strength was mainly attributed to the refinement of the bainitic ferrite laths and the high accumulation of dislocations within both the bainitic ferrite and retained austenite. The more stable retained austenite improved the sustainable work-hardening capability via the continuous transformation-induced plasticity effect.

Abstract Background Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS–STING in SAP-induced lung injury (LI) remains unknown. Methods Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS −/− and sting −/− mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro. Results SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA–cGAS–STING axis and the NLRP3–pyroptosis axis. Conclusions Negative regulation of any molecule in the mtDNA–cGAS–STING–IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.

Abstract Background Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. Methods From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. Results In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P

Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multicenter, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL- 5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment timepoints. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.

Abstract Background Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. Methods This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. Results Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. Conclusions These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Abstract To assess the damage and fracture behavior of wood under load, a wood damage assessment method was proposed based on acoustic emission (AE) b-values and seismic magnitude difference entropy. First, AE signals from Pinus sylvestris var. mongolica (softwood) and Zelkova schneideriana (hardwood) specimens were collected separately at a sampling frequency of 500 kHz in a three-point bending test. Then, 52 dB was taken as the threshold of the AE event, and the b-value and seismic magnitude difference entropy were calculated at 4-s intervals. Finally, by comparing with the load‒time curve, the b-value and seismic magnitude difference entropy were used to evaluate the damage fracture degree. The results showed that an increase in the b-value indicates the accumulation of strain energy, and vice versa, corresponding to the concentrated release of strain energy. At the same time, the test process can be divided into three stages—elastic, elastic‒plastic and plastic—based on the level of the seismic magnitude difference entropy.

Precipitation hardening serves as a viable mechanism to enhance the strength of high/medium entropy alloys (H/MEAs). The nature of precipitates in HEAs varies based on the composition of multiple principal elements. In order to further enhance the performance of HEAs across different applications, it becomes imperative to exercise control over phase synthesis and suppress the precipitation of detrimental phases. In this investigation, we propose a strategy for regulating the precipitation of the second phase in (Co, Cr)58Ni30Mo6Al6 (Co/Cr ratio = 1, 1.5, 2, 3) HEAs. Through precise adjustment of atomic ratios, the detrimental σ and μ phases are effectively restrained, while coherent nanoprecipitates are achieved through subsequent aging treatment. These fine nanoscale coherent phases alter the mode of dislocation slip, transforming planar slip into cross-slip, thereby providing a novel mechanism for the strengthening of the alloy. This controlled elimination and precipitation of phase contributes to a hierarchical improvement in the mechanical tensile properties. The aged HEA exhibits exceptional characteristics, including a strength of 1.3 GPa and 31% plasticity at 298 K (1.67 GPa and 40% at 77 K).

Objective: The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.Methods: First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.Result: 1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (P

Background Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFRcystatin C/eGFRcreatinine ratio 0.85, eGFRcystatin C/eGFRcreatinine≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18–3.21, p 0.85 (OR = 1.86, 95%CI = 1.08–3.21, p = 0.03).Conclusions In the current study, no significant association between SPS and FRS was identified. However, lower eGFRcystatin C/eGFRcreatinine and eGFRcystatin C/eGFRcreatinine≤0.85 were associated with a significantly increased CVD risk in T2DM.

BackgroundPneumonia and lung cancer have a mutually reinforcing relationship. Lung cancer patients are prone to contracting COVID-19, with poorer prognoses. Additionally, COVID-19 infection can impact anticancer treatments for lung cancer patients. Developing an early diagnostic system for COVID-19 pneumonia can help improve the prognosis of lung cancer patients with COVID-19 infection.MethodThis study proposes a neural network for COVID-19 diagnosis based on non-enhanced CT scans, consisting of two 3D convolutional neural networks (CNN) connected in series to form two diagnostic modules. The first diagnostic module classifies COVID-19 pneumonia patients from other pneumonia patients, while the second diagnostic module distinguishes severe COVID-19 patients from ordinary COVID-19 patients. We also analyzed the correlation between the deep learning features of the two diagnostic modules and various laboratory parameters, including KL-6.ResultThe first diagnostic module achieved an accuracy of 0.9669 on the training set and 0.8884 on the test set, while the second diagnostic module achieved an accuracy of 0.9722 on the training set and 0.9184 on the test set. Strong correlation was observed between the deep learning parameters of the second diagnostic module and KL-6.ConclusionOur neural network can differentiate between COVID-19 pneumonia and other pneumonias on CT images, while also distinguishing between ordinary COVID-19 patients and those with white lung. Patients with white lung in COVID-19 have greater alveolar damage compared to ordinary COVID-19 patients, and our deep learning features can serve as an imaging biomarker.

Abstract Purpose The aim of this study was to assess the potential application of a radiomics features‐based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high‐risk non‐metastatic prostate cancer (PCa). Methods Clinicopathologic information was retrospectively collected from 162 patients with high‐risk non‐metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. Results Sixty‐three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754–0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739–0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839–0.954). The Hosmer–Lemeshow goodness‐of‐fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan–Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. Conclusion The radiomics–clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high‐risk non‐metastatic PCa.

The aim of this investigation was to reveal the pattern of disposal process of thiamphenicol (TAP) in Chinese soft-shelled turtle after oral (PO) and intramuscular (IM) administration routes. TAP concentration levels in Chinese soft-shelled turtle plasma and multi-tissues were measured by HPLC-MS/MS. Pharmacokinetic (PK) parameters of TAP were estimated using WinNolin software based on the non-compartmental analysis. Compared with IM route, higher absorption, longer elimination time and greater AUC0-∞ value for TAP in plasma were observed after PO treatment. It indicated that Chinese soft-shelled turtle has a higher bioavailability for TAP following PO administration than IM medication. For tissue distribution, higher TAP concentrations were also found following PO medication than IM administration. The prescribed medication dosage of TAP (17.5 mg/kg bw) against susceptible strains with MIC should be below 0.22 mg/L (PO) and 0.13 mg/L (IM) based on the values of Cmax/MIC >10 and AUC0–24 h/MIC >125. TAP elimination pattern was investigated, and skirt was suggested as residual target tissue. Withdrawal time (WT) of TAP was calculated using WT 1.4 software, and the recommended WT was 17 d (391 ℃-day). The present investigation can serve as reference data for TAP use in Chinese soft-shelled turtle.