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Spectroscopic data, particularly diffraction data, are essential for materials characterization due to their comprehensive crystallographic information. The current crystallographic phase identification, however, is very time consuming. To address this challenge, we have developed a real-time crystallographic phase identifier based on a convolutional self-attention neural network (CPICANN). Trained on 692 190 simulated powder X-ray diffraction (XRD) patterns from 23 073 distinct inorganic crystallographic information files, CPICANN demonstrates superior phase-identification power. Single-phase identification on simulated XRD patterns yields 98.5 and 87.5% accuracies with and without elemental information, respectively, outperforming JADE software (68.2 and 38.7%, respectively). Bi-phase identification on simulated XRD patterns achieves 84.2 and 51.5% accuracies, respectively. In experimental settings, CPICANN achieves an 80% identification accuracy, surpassing JADE software (61%). Integration of CPICANN into XRD refinement software will significantly advance the cutting-edge technology in XRD materials characterization.

Coproporphyrin III (CP III), a natural porphyrin derivative, has extensive applications in the biomedical and material industries. S. cerevisiae has previously been engineered to highly accumulate the CP III precursor 5-aminolevulinic acid (ALA) through the C4 pathway. In this study, a combination of cytoplasmic metabolic engineering and mitochondrial compartmentalization was used to enhance CP III production in S. cerevisiae. By integrating pathway genes into the chromosome, the CP III titer gradually increased to 32.5 ± 0.5 mg/L in shake flask cultivation. Nevertheless, increasing the copy number of pathway genes did not consistently enhance CP III synthesis. Hence, the partial synthesis pathway was compartmentalized in mitochondria to evaluate its effectiveness in increasing CP III production. Subsequently, by superimposing the mitochondrial compartmentalization strategy on cytoplasmic metabolic engineered strains, the CP III titer was increased to 64.3 ± 1.9 mg/L. Furthermore, augmenting antioxidant pathway genes to reduce reactive oxygen species (ROS) levels effectively improved the growth of engineered strains, resulting in a further increase in the CP III titer to 82.9 ± 1.4 mg/L. Fed-batch fermentations in a 5 L bioreactor achieved a titer of 402.8 ± 9.3 mg/L for CP III. This study provides a new perspective on engineered yeast for the microbial production of porphyrins.

Highlights A unique approach is proposed: constructing a polymer fiber rigid network with high glass transition temperature. Frozen bulk heterojunction morphology impeded deterioration of exciton quenching, charge transport, and charge extraction properties during thermal aging. The strategy is universal and can be further optimized for enhanced thermal stability and improved mechanical resilience.

Abstract The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

Abstract Obstructive sleep apnea syndrome (OSAS), characterized by chronic intermittent hypoxia (CIH), is an independent risk factor for aggravating non‐alcoholic steatohepatitis (NASH). The prevailing mouse model employed in CIH research is inadequate for the comprehensive exploration of the impact of CIH on NASH development due to reduced food intake observed in CIH‐exposed mice, which deviates from human responses. To address this issue, a pair‐feeding investigation with CIH‐exposed and normoxia‐exposed mice is conducted. It is revealed that CIH exposure aggravates DNA damage, leading to hepatic fibrosis and inflammation. The analysis of genome‐wide association study (GWAS) data also discloses the association between Eepd1, a DNA repair enzyme, and OSAS. Furthermore, it is revealed that CIH triggered selective autophagy, leading to the autophagic degradation of Eepd1, thereby exacerbating DNA damage in hepatocytes. Notably, Eepd1 liver‐specific knockout mice exhibit aggravated hepatic DNA damage and further progression of NASH. To identify a therapeutic approach for CIH‐induced NASH, a drug screening is conducted and it is found that Retigabine dihydrochloride suppresses CIH‐mediated Eepd1 degradation, leading to alleviated DNA damage in hepatocytes. These findings imply that targeting CIH‐mediated Eepd1 degradation can be an adjunctive approach in the treatment of NASH exacerbated by OSAS.

During liver regeneration, especially after a hepatectomy, hepatocytes experience significant lipid accumulation. These transiently accumulated lipids are generally believed to provide substrates for energy supply or membrane biomaterials for newly generated hepatocytes. Remarkably, a recent study found that acute lipid accumulation during regeneration can act as a signal for chromatin remodeling to regulate regeneration. Chen, Y.H., et al. identified MIER1 (mesoderm induction early response protein 1) as a crucial inhibitor of liver regeneration through in vivo CRISPR screening. MIER1 binds to and restrains cell cycle genes’ expression. During liver regeneration, acute lipid accumulation suppresses MIER1 translation via the EIF2S pathway, resulting in transient down-regulation of MIER1 protein, which promotes cell cycle gene expression and liver regeneration. Interestingly, the researchers also found that the dynamic regulation of MIER1 was impaired in fatty and aging livers with chronic steatosis, while of knockout of MIER1 in these animals improved their regenerative capacity. In conclusion, this study provides valuable insights into the complex mechanisms underlying liver regeneration and highlights the potential therapeutic applications of targeting MIER1 for improving liver regeneration in disease states associated with impaired lipid homeostasis.

The steady increase in the prevalence of inflammatory bowel disease (IBD) is regarded as a worldwide health issue. Gut microorganisms could modulate host immune and metabolic status and are associated with health effects. Probiotics, Lactobacillus rhamnosus GG (LGG), are beneficial microorganisms that ameliorate disease and exert advantageous effects on intestinal homeostasis. However, the viability of probiotics will suffer from various risk factors in the digestive tract. In this view, we developed a probiotic coating with nanocomposite using tannic acid (TA) and casein phosphopeptide (CPP) through layer-by-layer technology to overcome the challenges after oral administration. LGG showed an improved survival rate in simulated gastrointestinal conditions after coated. The coating (LGG/TA-Mg2+/CPP) had potent reactive oxygen species (ROS) scavenging ability and improved the survival rate of colorectal epithelial cells after H2O2 stimulation. In DSS-induced colitis, administration of LGG/TA-Mg2+/CPP ameliorated intestinal inflammation and reduced the disruption of barrier function. Furthermore, LGG/TA-Mg2+/CPP increased the abundance and diversity of the gut microbiota. In the mouse model of DSS colitis, LGG/TA-Mg2+/CPP can better activate the EGFR/AKT signaling pathway, thereby protecting the epithelial barrier function of the colon epithelium. In conclusion, the probiotic coating with nanocomposite may become a delivery platform for probiotics applied to IBD.

Intensive application of chlorine-based disinfectants driven by the COVID-19 pandemic was suspected to be detrimental to receiving water ecosystems, but with little field evidence. We characterized the occurrences of typical disinfectants and microeukaryotic communities in surface waters associated with three wastewater treatment plants (WWTP)-river systems one year after the lockdown in Wuhan, China. Trihalomethanes (THMs) declined from summer 2020 (0.01–1.82 ​μg/L) to summer 2021 (0.01–0.95 ​μg/L), whereas quaternary ammonium salts (QAs) increased from summer 2020 (0.53–6.35 ​ng/L) to summer 2021 (8.49–191 ​ng/L). Biodiversity monitoring with environmental DNA (eDNA) revealed significant temporal variation in microeukaryotic community composition. The monitored disinfectants were correlated with some eukaryotic communities as demonstrated by redundancy analysis. For example, QAs were positively related to Cryptophyta relative abundance, but negatively related to Rotifera relative abundance. A microeukaryote-based multimetric index indicated ecological impairment near the Han River WWTP outlet in 2020. Our findings indicate the influence of heavily used disinfectants on river microeukaryotic communities, and the usefulness of assessing mid-term ecological risks from disinfectants in the post COVID-19 era.

Ciliated microeukaryotes (ciliates) are distinguished by their cilia, which are rich in tubulin. We developed a method for tubulin staining in ciliate cells that involves using live-cell tubulin-staining dyes instead of antibodies thereby streamlining the staining process, which is effective across diverse ciliate lineages. Moreover, our method allows integration with immunofluorescence staining using antibodies when needed. The potential applications of this technique extend to cell biology and ciliate morphological and ecological studies.

Abstract Introduction The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. Methods This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. Planned Outcome The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. Conclusion This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. Trial Registration ClinicalTrials.gov identifier, NCT05359601.

Objective The inversion of magnetotelluric sounding data to improve the accuracy of data interpretation has always been an essential topic in magnetotelluric sounding. Methods To address the problems of traditional magnetotelluric inversion methods, such as the dependence of the initial model and the ease of falling into a local optimum, this paper proposes a magnetotelluric inversion method based on deep learning.The method begins with the design of the GoogLeNetINV neural network. Then, various geoelectric models are constructed, and apparent resistivity data are extracted via forward modelling in the TM mode, constituting the training dataset. Additionally, the neural network is trained with the training dataset, and the network parameters are adjusted. Finally, the apparent resistivity data are input into the trained GoogLeNetINV neural network to directly obtain the inversion result. Results The experimental results reveal that the location and resistivity data of the "unlearned" geoelectric model can be inverted quickly and accurately, and the model has good generalization ability. The use of noise data can still yield good inversion results and a certain anti-noise ability. Conclusion The neural network is applied to the field data processing of the Bendigo Zone, and the resistivity model derived through inversion is consistent with the seismic interpretation. Consequently, the magnetotelluric inversion method based on deep learning can effectively solve the magnetotelluric inversion problem.

Abstract Balantidium ctenopharyngodoni is identified as the sole ciliate species that exclusively resides within the hindgut of grass carp with high prevalence and intensity. In this study, the successful cultivation of B. ctenopharyngodoni enabled us to collect enough cells for genome sequencing. Consequently, we acquired a high-quality genome assembly spanning 68.66 Mb, encompassing a total of 22,334 nanochromosomes. Furthermore, we predicted 29,348 protein-coding genes, and 95.5% of them was supported by the RNA-seq data. The trend of GC content in the subtelomeric regions of single-gene chromosomes was similar to other ciliates containing nanochromosomes. A large number of genes encoding carbohydrate-binding modules with affinities for starch and peptidoglycans was identified. The identification of mitochondrion-related organelles (MROs) within genome indicates its well-suited adaptation to the anaerobic conditions in the hindgut environment. In summary, our results will offer resources for understanding the genetic basis and molecular adaptations of balantidia to hindgut of herbivorous fish.

Abstract Accelerating the discovery of advanced materials is crucial for modern industries, aerospace, biomedicine, and energy. Nevertheless, only a small fraction of materials are currently under experimental investigation within the vast chemical space. Materials scientists are plagued by time-consuming and labor-intensive experiments due to lacking efficient material discovery strategies. Artificial intelligence (AI) has emerged as a promising instrument to bridge this gap. Although numerous AI toolkits or platforms for material science have been developed, they suffer from many shortcomings. These include primarily focusing on material property prediction and being unfriendly to material scientists lacking programming experience, especially performing poorly with limited data. Here, we developed MLMD, an AI platform for materials design. It is capable of effectively discovering novel materials with high-potential advanced properties end-to-end, utilizing model inference, surrogate optimization, and even working in situations of data scarcity based on active learning. Additionally, it integrates data analysis, descriptor refactoring, hyper-parameters auto-optimizing, and properties prediction. It also provides a web-based friendly interface without need programming and can be used anywhere, anytime. MLMD is dedicated to the integration of material experiment/computation and design, and accelerate the new material discovery with desired one or multiple properties. It demonstrates the strong power to direct experiments on various materials (perovskites, steel, high-entropy alloy, etc). MLMD will be an essential tool for materials scientists and facilitate the advancement of materials informatics.

Abstract Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24–74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43–79%) and 68% (95%CI, 47–84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45–83%) and 86% (95%CI, 63–95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

Abstract Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region. Furthermore, OTUD1-based aggresomes recruit ASK1 via protein-protein interactions, which in turn stabilize ASK1 in a deubiquitinase-independent manner and activate the downstream JNK signaling pathway for OCSC maintenance. Notably, the disruption of OTUD1-based aggresomes or treatment with ASK1/JNK inhibitors, including ibrutinib, an FDA-approved drug that was recently identified as an MKK7 inhibitor, effectively reduced OCSC stemness (OSCS) of OTUD1high ovarian cancer cells. In summary, our work suggests that aggresome formation in tumor cells could function as a signaling hub and that aggresome-based therapy has translational potential for patients with OTUD1high ovarian cancer.

Abstract The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome’s biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.

Natural Language Processing (NLP) technology is rapidly evolving, and various large language models have been widely applied in Legal Artificial Intelligence (AI). However, low accuracy in Similar Case Matching (SCM) persists in the most popular case recommendation systems. It hinders the practical application of case recommendations in Legal Judgment Prediction (LJP). Developing effective methods to extract features from long texts and improve the accuracy of SCM is an urgent matter that requires attention. Therefore, the paper proposes a SCM method based on deep text comprehension. A fine-tuned BERT model is used to extract text information, and a combination of global attention and self-attention is employed to represent the features of long texts deeply. A dual-channel similar text-matching approach is used after candidate texts are pre-encoded to reduce the SCM model’s training time and improve accuracy. Experiments on the China AI and Law (CAIL) competition dataset show that the proposed method achieves the highest accuracy in SCM compared to the recent methods.

Since the release of ChatGPT, large language models (LLMs) have played a huge role in various industries. In the field of games, we have used LLMs to act as intelligent AI NPC, which makes NPCs more intelligent. However, there is still an obvious obstacle -the LLMs lacks long-term memory and human-like memory mechanism. This flawed memory mechanism prevents NPCs from Long-term interaction and humanized memory based on conversation records. Recognizing the necessity of long-term memory and humanized memory, we proposed MemoryRepository, a memory mechanism for LLMs specifically used in the AI NPC field.MemoryRepository enables the model to have short-term memory and long-term memory. Short-term memory is more detailed and full, while long-term memory are more concise and partial. MemoryRepository is inspired by human memory and forgetting mechanisms. This mechanism allows AI NPCs to forget and summarize past conversation records, thereby providing long-term interaction capabilities. More importantly, this process of forgetting and summarizing the details of short-term memory into general long-term memories makes NPCs more human-like. MemoryRepository is versatile and can adapt to closed source models such as ChatGPT and open source models such as ChatGLM. To Intuitively verify the effectiveness of MemoryRepository in the field of AI NPC, we created an example in which all NPCs are represented by LLMs adapted to MemoryRepository. The example shows that by embedding LLM in MemoryRepository and fine-tuning NPCs character dialogue data, AI NPC can conduct better long-term conversations and appear more human-like during the interaction process. To validate the effectiveness of MemoryRepository, one hundred pieces of NPCs dialogue data were created and then quantitatively analyzed through evaluation indicators. The analysis results show that NPCs equipped with MemoryRepository can summarize and forget past memories, which enables it to have the ability to hold long-term conversations and conduct more human-like conversations.

The rumen ciliates are a diverse group of protozoa residing in the rumen of ruminant animals. They are primarily found in the orders Entodiniomorphida and Vestibuliferida, playing crucial roles in the digestion and breakdown of feed within the host's rumen, closely intertwined with the host's nutrient absorption. In vitro monocultures of representatives of rumen ciliates are important to better study them. So far, Entodinium caudatum and Epidinium caudatum, representatives of the order Entodiniomorphida, have been successfully cultivated as a monoculture in vitro. However, for the order Vestibuliferida, no representative species has been established a stable monoculture in vitro up to date, which hampers to study their physiology and metabolism. Therefore, we have developed a simple method for the in vitro cultivation of Dasytricha ruminantium, a representative rumen ciliate in the order Vestibuliferida. Utilizing an optimized culture medium with easily obtainable components, and the cultivation process is simple. This will facilitate further research in metabolism and other studies requiring large pure live materials. 1. Filtration and separation for enriching D. ruminantium. 2. A culture medium (DRM) suitable for the growth of D. ruminantium, with easily obtainable components. 3. Simple cultivation process, facilitating the obtainment of a large number of monocultured D. ruminantium.

Abstract All‐solid‐state batteries (ASSBs) based on inorganic solid electrolytes fascinate a large body of researchers in terms of overcoming the inferior energy density and safety issues of existing lithium‐ion batteries. To date, the cathode designs in the ASSBs achieve remarkable achievements, adding the urgency of scaling up the battery system toward inorganic solid‐state pouch cell configuration for the application market. Herein, the recent developments of cathode materials and the design considerations for their application in the pouch cell format are reviewed to straighten out the roadmap of ASSBs. Specifically, the intercalation compounds and the conversion materials with conversion chemistries are highlighted and discussed as two potentially valuable material types. This review focuses on the basic electrochemical mechanisms, mechanical contact issues, and sheet‐type structure in inorganic solid‐state pouch cells with corresponding perspectives, thus guiding the future research direction. Finally, the benchmarks for manufacturing inorganic solid‐state pouch cells to meet practical high energy density targets are provided in this review for the development of commercially viable products.

BRASH syndrome is a vicious cycle of hyperkalemia and bradycardia and is an under-recognized life-threatening clinical diagnosis. It is usually initiated by hypovolemia or hyperkalemia. We report here on the case of a 92-year-old man with hypertension and heart failure who presented to the emergency department with weakness following diarrhea. He was on amlodipine, benazepril, metoprolol, furosemide and spironolactone. The patient’s blood pressure was 88/53 mmHg and the serum creatinine was 241 μmol/L. Within 2 h, the patient’s heart rate decreased from 58 beats per minute to 26 beats per minute, and serum potassium levels gradually increased from 6.07 mmol/L to 7.3 mmol/L. The electrocardiogram showed a junctional escape rhythm with accidental sinus capture. The diagnosis of BRASH syndrome was made based on clinical symptoms, a biochemical profile and the results of an electrocardiogram. The patient was rapidly stabilized with the administration of intravenous calcium gluconate, dextrose and insulin, 5% sodium bicarbonate, 0.9% sodium chloride, furosemide, and oral zirconium cyclosilicate. Sinus rhythm at a heart rate of 75 bpm was detected 5 h later, along with normal serum potassium levels. After 2 weeks, kidney function returned to normal. Clinicians should be alert to patients with hyperkalemia and maintain a high index of suspicion for BRASH syndrome. Timely diagnosis and comprehensive intervention are critical for better outcomes in managing patients with BRASH.

Purpose This study aims to systematically review the efficacy and safety of total ankle replacement (TAR) and ankle fusion (AF) as treatment options for end-stage ankle arthritis. Methods A comprehensive literature search was conducted on data from multiple databases, including PubMed, The Cochrane Library, Construction and Building Materials, Embase, Web of Science, and Scopus for RCTs and prospective cohort studies comparing TAR and AF in patients with end-stage ankle arthritis from inception up to June, 2023. Our primary outcomes of interest included patients’ clinical function scores and complications. We employed Review Manager 5.4 and Stata/MP 14.0 software for the meta-analysis. Results Our analysis incorporated 13 comparative studies, including 11 prospective studies, one pilot RCT, and one RCT. The pooled results revealed no significant difference in postoperative Short Form-36 scores between the TAR and AF groups (MD = −1.19, 95% CI: −3.89 to 1.50, p = .39). However, the postoperative Foot and Ankle Ability Measure scores in the AF group were significantly higher than in the TAR group (MD = 8.30, 95% CI: 1.01–15.60, p = .03). There was no significant difference in postoperative complication rates between the TAR and AF groups (RR = 0.95, 95% CI: 0.59 to 1.54, p = .85). Conclusion Currently available evidence suggests no significant disparity in postoperative outcomes between TAR and AF. In the short term, TAR demonstrates better clinical scores than AF and lower complication rates. Conversely, in the long term, AF exhibits superior clinical scores and lower complication rates, although this difference is not statistically significant.

Abstract Background The effects of diabetes on the cardiac and aortic structure and function remain unclear. Detecting and intervening these variations early is crucial for the prevention and management of complications. Cardiovascular magnetic resonance imaging-derived traits are established endophenotypes and serve as precise, early-detection, noninvasive clinical risk biomarkers. We conducted a Mendelian randomization (MR) study to examine the association between two types of diabetes, four glycemic traits, and preclinical endophenotypes of cardiac and aortic structure and function. Methods Independent genetic variants significantly associated with type 1 diabetes, type 2 diabetes, fasting insulin (FIns), fasting glucose (FGlu), 2 h-glucose post-challenge (2hGlu), and glycated hemoglobin (HbA1c) were selected as instrumental variables. The 96 cardiovascular magnetic resonance imaging traits came from six independent genome-wide association studies. These traits serve as preclinical endophenotypes and offer an early indication of the structure and function of the four cardiac chambers and two aortic sections. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using the weighted median, MR-Egger, and MR-PRESSO methods. Additionally, multivariable MR was used to adjust for potential effects associated with body mass index. Results Genetic susceptibility to type 1 diabetes was associated with increased ascending aortic distensibility. Conversely, type 2 diabetes showed a correlation with a reduced diameter and areas of the ascending aorta, as well as decreased distensibility of the descending aorta. Genetically predicted higher levels of FGlu and HbA1c were correlated with a decrease in diameter and areas of the ascending aorta. Furthermore, higher 2hGlu levels predominantly showed association with a reduced diameter of both the ascending and descending aorta. Higher FIns levels corresponded to increased regional myocardial-wall thicknesses at end-diastole, global myocardial-wall thickness at end-diastole, and regional peak circumferential strain of the left ventricle. Conclusions This study provides evidence that diabetes and glycemic traits have a causal relationship with cardiac and aortic structural and functional remodeling, highlighting the importance of intensive glucose-lowering for primary prevention of cardiovascular diseases.

Abstract Background Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development. Methods The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were used to search the downstream genes and pathways of RCC2 in mediated PCa progression. Western blot was used to detect the proteins in PCa cells transfected with indicated siRNAs or plasmids. Results RCC2 had high expression and low promoter methylation level in PCa, and its expression was correlated with regional node metastasis and disease-free survival. Cell proliferation, migration, invasion and EMT of PCa cells in vitro were greatly enhanced after RCC2 overexpression, while the RCC2 knockdown suppressed these processes. RNA-seq and GSEA results showed the Hedgehog signaling regulator Gli1 and Gli3 were involved in RCC2 knockdown DU145 cells. Gli1 was also a marker of cancer stem-like cells (CSCs). Mechanistically, RCC2 induced cell growth, EMT, CSCs markers through Gli1; inhibiting Gli1 expression using siGli1 or GLI inhibitor suppressed cell progression in vitro and tumor growth in vivo. Conclusion In summary, RCC2 promoted PCa development through Hh/Gli1 signaling pathway via regulating EMT and CSCs.

Light penetration depth, as a characteristic parameter reflecting light attenuation and transmission in biological tissues, has been applied in nondestructive detection of fruits and vegetables. Recently, with emergence of new optical detection technologies, researchers have begun to explore methods evaluating optical properties of double-layer or even multilayer fruit and vegetable tissues due to the differences between peel and pulp in the chemical composition and physical properties, which has gradually promoted studies on light penetration depth. A series of demonstrated research on light penetration depth could ensure the accuracy of the optical information obtained from each layer of tissue, which is beneficial to enhance detection accuracy for quality assessment of fruits and vegetables. Therefore, the aim of this review is to give detailed outlines about the theory and principle of light penetration depth based on several emerging optical detection technologies and to focus primarily on its applications in the field of quality evaluation of fruits and vegetables, its future applicability in fruits and vegetables and the challenges it may face in the future.

Leaf angle (LA) is an important trait of plant architecture, and individuals with narrow LA can better capture canopy light under high-density planting, which is beneficial for increasing the overall yield per unit area. To study the genetic basis and molecular regulation mechanism of leaf angle in rapeseed, we carried out a series of experiments. Quantitative trait loci (QTL) mapping was performed using the RIL population, and seven QTLs were identified. Transcriptome analysis showed that the cell wall formation/biogenesis processes and biosynthesis/metabolism of cell wall components were the most enrichment classes. Most differentially expressed genes (DEGs) involved in the synthesis of lignin, xylan, and cellulose showed down-regulated expression in narrow leaf material. Microscopic analysis suggested that the cell size affected by the cell wall in the junction area of the stem and petiole was the main factor in leaf petiole angle (LPA) differences. Combining QTL mapping and RNA sequencing, five promising candidate genes BnaA01G0125600ZS, BnaA01G0135700ZS, BnaA01G0154600ZS, BnaA10G0154200ZS, and BnaC03G0294200ZS were identified in rapeseed, and most of them were involved in cell wall biogenesis and the synthesis/metabolism of cell wall components. The results of QTL, transcriptome analysis, and cytological analysis were highly consistent, collectively revealing that genes related to cell wall function played a crucial role in regulating the LA trait in rapeseed. The study provides further insights into LA traits, and the discovery of new QTLs and candidate genes is highly beneficial for genetic improvement.

Isoliquiritigenin (ISL) has excellent neuroprotective effects. However, its limitations, including poor solubility, low bioavailability, and low accumulation in the brain, restrict its clinical promotion. In this study, a novel type of ISL-loaded liposome (ISL-LP) modified with the brain-targeting polypeptide angiopep-2 was prepared to improve these properties. The zeta potential, morphology, particle size, encapsulation efficiency, drug loading, and in vitro release of ISL-LP were evaluated. The pharmacokinetics and tissue distribution of ISL and ISL-LP were also investigated. The results demonstrated that ISL-LP had an average particle size of 89.36 ± 5.04 nm, a polymer dispersity index of 0.17 ± 0.03, a zeta potential of −20.27 ± 2.18 mV, and an encapsulation efficiency of 75.04 ± 3.28%. The in vitro release experiments indicate that ISL-LP is a desirable sustained-release system. After intravenous administration, LPC-LP prolonged the circulation time of ISL in vivo and enhanced its relative brain uptake. In conclusion, ISL-LP could serve as a promising brain-targeting system for the treatment and prevention of central nervous system (CNS) disorders.

Using finite element simulation and single-variable experimental methods, this study analyzes the variations in the microstructure and hardness of a 304 stainless steel wire during Joule heating fused filament fabrication. The effects of current intensity, printing speed, and roller pressure on the macroscopic morphology, microstructure, and microhardness of a single-layer single-channel formation were investigated. The results indicate that when the current intensity is 400 A, the printing speed is 1000 mm/min, and the roller pressure is 0.3 N, the surface of the single-layer single-channel formation is smooth and exhibits optimal forming characteristics with a width-to-height ratio of 3.23, a dilution rate of 51.61%, and an average microhardness of 238.17 HV. As the current intensity increases, the microstructure in the fusion zone initially decreases in size and then increases; similarly, with the increase in printing speed, the microstructure in the fusion zone first decreases and then increases; as the roller pressure increases, the microstructure in the fusion zone initially increases in size and then decreases. The microhardness initially increases and then decreases with the increase in process parameters, resulting in uneven hardness distribution due to the variations in microstructure size. The optimal combination of process parameters achieves a balance between heat input, cooling rate, and growth rate, thereby achieving grain refinement and hardness improvement, ultimately enhancing the mechanical properties of the material.

Although most species have two sexes, multisexual (or multi-mating type) species are also widespread. However, it is unclear how mating-type recognition is achieved at the molecular level in multisexual species. The unicellular ciliate Tetrahymena thermophila has seven mating types, which are determined by the MTA and MTB proteins. In this study, we found that both proteins are essential for cells to send or receive complete mating-type information, and transmission of the mating-type signal requires both proteins to be expressed in the same cell. We found that MTA and MTB form a mating-type recognition complex that localizes to the plasma membrane, but not to the cilia. Stimulation experiments showed that the mating-type-specific regions of MTA and MTB mediate both self- and non-self-recognition, indicating that T. thermophila uses a dual approach to achieve mating-type recognition. Our results suggest that MTA and MTB form an elaborate multifunctional protein complex that can identify cells of both self and non-self mating types in order to inhibit or activate mating, respectively.

The determination of ductile-to-brittle transition temperatures (DBTT) in intermetallic compounds is crucial for assessing their practical applications. In this study, we investigate the intrinsic factors influencing the DBTT of Fe–Al intermetallic compounds through feature engineering. We developed and evaluated two machine learning strategies for this task. Comparing the strategy that incorporates all features, including alloy compositions and atomic features, with the strategy utilizing selected features, it is found that the latter demonstrates superior computational efficiency and reduces overfitting. Specifically, surrogate models based on two selected features, namely cohesive energy and ionization energy, enable accurate prediction of the DBTT of Fe–Al intermetallics, achieving an accuracy of 95%. Additionally, through symbolic regression, we derived a functional expression that captures the relationship between variations in the DBTT and the selected features of intermetallic compounds. These findings have the potential to serve as a valuable guide for optimizing intermetallic compounds.

Posterior olecranon fracture dislocations (POFDs) were considered posterior Monteggia lesions, which were less described in the literature. The purpose of this study was to provide a systematic review of the diagnosis, treatment, prognosis, and complications of POFDs in adults. A systematic review was performed to identify all relevant studies on the POFDs in the PubMed, Web of Science, Embase, and MEDLINE databases. The methodological quality of the studies was scored using the Methodological Index for Non‐Randomized Studies (MINORS). A total of 117 patients were identified in the nine studies selected. The high‐energy injuries accounted for 42.7% of the included studies. The rates of concomitant coronoid process, radial head fractures, and lateral collateral ligament injury were 84.6% (99/117), 87.2% (102/117), and 5% (6/117), respectively. The procedure was performed with a dorsal mid longitudinal approach to reconstruct all injury components. The postoperative clinical scores included the Broberg/Morrey rating, with a mean rating of excellent or good at 66%, the mean DASH score was 20.6, and the mean ASES score was 83. The flexion and extension arc and forearm rotation arcs were 100° and 134°, respectively. Complications included arthrosis in 28.2% (33/117) of cases, fracture nonunion or delayed union in 9.4% (11/117) of cases, heterotopic ossification in 7% (8/117) of cases, and the re‐operation rate was 16% (19/117). There was nearly no postoperative ulnohumeral instability. The main characteristics of POFDs were disruptions of the trochlear notch, including the olecranon and coronoid processes, and severe radial head fractures, while the lateral collateral ligament was spared. Although the POFDs had a low frequency of instability, the prognosis was relatively poor. The POFDs should be considered independently.

Abstract Background Traditional estimates can only provide static predictions of cancer outcomes and cannot assess the evolving effect of race on patient survival. This study aims to reveal the dynamic survival of patients with bladder cancer and to explore the evolving effect of race on patient prognosis. Methods Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, 99,590 white, 6,036 African American, and 4,685 Asian/Pacific Islander (API) patients with bladder cancer were identified. Conditional cancer-specific survival (CSS) rates, which could reflect the dynamic survival prediction of cancer patients, represented the primary outcomes, and were estimated by the Kaplan-Meier algorithm. The evolving effect of race on patient survival was evaluated by multivariable Cox regression in combination with conditional survival (CS) estimates. Results The 5-year CSS for African American patients who had survived 1, 2, 3, 4, or 5 years after definitive therapy improved from the baseline calculation by + 5.8 (84.4%), + 9.5 (87.4%), + 12.8 (90.0%), + 14.4 (91.3%), and + 14.7% (91.5%), respectively. The increasing trend also held for overall white and API patients, and for all patient subsets when CS was calculated according to different levels of sex, age, and disease stage. African Americans, despite having the worst survival at baseline, could have CSS comparable to their white and API counterparts after 4 years of survivorship. In addition, the risk of death for African Americans tended to decrease with increasing survival, and the risk was no longer significantly different from that of whites after 4 years of survival. Conclusions While having the worst initial predicted outcomes, African Americans may eventually achieve comparable survival to white and API patients given several years of survivorship. As patient survival increases, African American race may lose its role as an indicator of poorer prognosis.

Abstract This study explores the effects of government subsidies on company labour productivity in strategic emerging industries under conditions of market power in downstream and upstream markets. A sample of 1392 listed companies from emerging industries in China from 2006 to 2019 is used. Labour productivity will be lower in companies with high seller power. The positive effect of subsidies on labour productivity will be enhanced when firms possess higher seller power, whereas the positive effect of subsidies on labour productivity will be weakened when firms possess higher buyer power. Heterogeneity analysis shows that the role of market power is more evident for domestic enterprises compared to foreign investment companies. The mechanisms of picking winners based on government subsidies should take the effects brought by various degrees of market power into account.

This study aimed to investigate the effect of Gnaphalium affine extract (GAE) (0.04, 0.2 and 1 mg/g protein) on the gel properties of porcine myofibrillar proteins (MPs) in a simulated Fenton oxidation system, using tea polyphenols (TPs) at similar concentrations of 0.04, 0.2, and 1 mg/g protein, respectively, as a contrast. The findings revealed that as the TP concentration increased, the water retention of MP gels decreased significantly (p < 0.05). In contrast, MP gels containing medium and high concentrations of GAE exhibited significantly higher water retention than those with low concentrations of GAE (p < 0.05). When the concentration of GAE was increased to 1 mg/g protein, the strength of MP gels was significantly reduced (p < 0.05) by 33.32% compared with the oxidized control group, suggesting that low and medium GAE concentrations support MP gel formation. A texture profile analysis indicated that an appropriate GAE concentration improved gel structure and texture. Dynamic rheological characterization revealed that low concentrations of TP (0.04 mg/g protein) and low and medium concentrations of GAE (0.04 and 0.2 mg/g protein) strengthened the protein gel system. Conversely, high concentrations of TP and GAE (1.0 mg/g protein) damaged the protein gel system or even promoted the collapse of the gel system. Scanning electron microscopy revealed that higher TP concentrations disrupted the gel, whereas low and medium GAE concentrations maintained a more continuous and complete gel network structure compared with the oxidized control group. This indicates that an appropriate GAE concentration could effectively hinder the destruction of the gel network structure by oxidation. Therefore, based on the obtained results, 0.2 mg/g protein is recommended as the ideal concentration of GAE to be used in actual meat processing to regulate the oxidization and gel properties of meat products.

A series of fullerene anisole derivative stabilizers was synthesized by nucleophilic substitution reaction using hexachlorofullerene and benzyl alcohol as raw materials to extend the service duration of nitrocellulose (NC)-based propellants. Single-crystal X-ray diffraction, nuclear magnetic resonance, high-resolution mass spectrometry, Fourier transform infrared (FT-IR) spectroscopy, and UV–Vis spectroscopy were used to characterize the structures of the synthesized fullerene anisole derivative stabilizers. Methyl violet, differential scanning calorimetry test, isothermal weight loss, vacuum stability test, and adiabatic accelerated test were used to study their compatibility with NC and their ability to stabilize NC. The results show that the designed and synthesized novel fullerene anisole derivative stabilizer has good compatibility with NC, and their overall stabilizing effects on NC are better than those of the traditional stabilizers, diphenylamine (DPA), and N,N′-dimethyl-N,N′-diphenylurea (C2). The stabilizing effects was ranked as: 3b > 2d > 2a > 2c > C2 > 2b > DPA > NC. In addition, FT-IR analysis and electron spin resonance spectroscopy were applied to explore the stability mechanism of fullerene-based stabilizers to NC. The results reveal that the new fullerene stabilizer can adsorb and effectively eliminate the nitrogen oxide free radicals generated by NC degradation; therefore, it can forbid the autocatalytic degradation of NC and stabilize NC.

Because of the small disturbance energy of random parameter in the rainstorm convective-allowing ensemble forecast model, a convective-allowing ensemble forecasting test based on WRFv3.9 model was carried out for a heavy rainstorm case in the Yangtze River Basin in China. The disturbance characteristics of various hybrid perturbation schemes of stochastically perturbed parameterization (SPP), stochastically perturbed parameterization tendencies (SPPT), and stochastic kinetic-energy backscatter (SKEB) were compared and analyzed, and the prediction effects of these schemes were evaluated. The main conclusions are as follows: the spread of meteorological elements of multi-stochastic physical disturbance in rainstorm convective-allowing ensemble forecast increases comparing to the single SPP scheme. The spread of SPP+SPPT+SKEB is the largest and the overall score is the best. The spread of surface meteorological elements of SPP+SPPT is larger than that of SPP+SKEB, while the spread of meteorological elements in the upper air (especially in the wind field) of SPP+SKEB is larger than that of SPP+SPPT. In the SPP+SPPT test, the spread of meteorological elements increased significantly at the initial stage of integration time, while the spread of meteorological elements at each altitude increased more prominently with the extension of integration time in the SPP+SKEB test. In terms of ensemble average, spread distribution and probability prediction skills, the hybrid perturbation scheme of multi-stochastic disturbance are better than those of the single SPP scheme. Overall, the SPP+SPPT+SKEB scheme performs the best. The SPP+SPPT+SKEB scheme integrate the advantages of SPP, SPPT and SKEB, and achieve the best spread of meteorological elements in the whole integration period of each altitude layer, because of the complementary effects of the hybrid perturbation of multi-stochastic disturbance schemes.

Abstract Background With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. Methods One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. Results Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 μg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). Conclusions Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality.

Abstract Backgrounds Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Deep understanding of chemoresistance will lead to remarkable progress in lung cancer treatment strategy. Cholesterol accumulation was associated with cisplatin resistance in lung cancer treatment. And we found the degree of cisplatin resistance was correlated with the expression of the cholesterol synthesis HMGCR. Methods We analyzed a group of 42 lung cancer patients who received cisplatin treatment after lung resection surgery. The expression of HMGCR and its correlation with cholesterol in lung cancer cell lines were determined by qRT-PCR and ELISA analyses. We focus on the function and mechanism of HMGCR in lung cancer and reveal that knockdown of HMGCR expression inhibits the proliferation, colony formation, and migration of lung cancer cell lines in vitro or in vivo and dramatically enhances the efficacy of cisplatin. Results Through mechanism studies, we illustrate that SIAH1, an E3 ubiquitin-protein ligase, ubiquitination modifies HMGCR and inhibits efflux protein activity via regulating cholesterol synthesis. In vivo experiments showed that SIAH1 overexpression or using HMGCR knockdown retard tumor growth and enhanced the efficacy of cisplatin. In summary, HMGCR affects cholesterol metabolism by regulating key enzymes in cholesterol synthesis, thereby reducing drug sensitivity. Conclusion This study indicates that lung cancer patients with lower HMGCR levels may lead to a better prognosis and provide a potential treatment by SIAH1 overexpression for lung cancer patients with cisplatin resistance.

Abstract Persistent corneal pain (PCP) has excellent research prospects, especially the central sensitization mechanism of the trigeminal nerve, which is involved in migraine, corneal pain, and trigeminal neuralgia. The cornea has dense sensory innervation, and repeated corneal neuropathic pain has been associated with trigeminal nerve central sensitization, which is induced in PCP. The calcitonin gene‐related peptide (CGRP) is involved in corneal pain conduction, injury protection, and immune homeostasis. A high CGRP level maintains corneal pain perception and protects corneal epithelial cells. However, a persistently high CGRP level causes hypersensitivity of the corneal and trigeminal nerves, resulting in PCP. CGRP‐related drugs can effectively improve trigeminal nerve sensitization and relieve central sensitization‐related pain (PCP, migraine, and trigeminal neuralgia). Exploring the role of CGRP in PCP's pain sensitization mechanism is vital in the pain perception field, with the potential to improve the quality of life of patients with PCP and strengthen the understanding of CGRP's dual role in corneal pain.

Abstract Extranodal natural killer/T‐cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein–Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single‐cell RNA sequencing (scRNA‐seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single‐cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV‐encoded genes and low infiltration of tumor‐associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single‐cell resolution, highlighting the crucial role of malignant NK cells with EBV‐encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.

Summary: Increased de novo lipogenesis (DNL) is a major feature of nonalcoholic steatohepatitis (NASH). None of the drugs targeting the catalytic activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the DNL process, have been approved by the FDA. Whether cytosolic ACC1 can be regulated spatially remains to be explored. Herein, we find that streptavidin (SA), which is a bacterium-derived tetrameric protein, forms cytosolic condensates and efficiently induces a spatial re-localization of ACC1 in liver cells, concomitant with inhibited lipid accumulation. Both SA tetrameric structure and multivalent protein interaction are required for condensate formation. Interestingly, the condensates are further characterized as gel-like membraneless organelle (SAGMO) and significantly restrict the cytosolic dispersion of ACC1 and fatty acid synthase. Notably, AAV-mediated delivery of SA partially blocks mouse liver DNL and ameliorates NASH without eliciting hypertriglyceridemia. In summary, our study shows that insulating lipogenesis-related proteins by SAGMO might be effective for NASH treatment.

Polysaccharides have recently garnered interest for their possible biological activity in treating colitis. In this work, we isolated a novel polysaccharide EPS-1 from yogurt, which comprises galactose and glucose (molar ratio = 42.04:57.96) and has a molecular weight of 32.60 kDa on average. The structure characterization revealed that EPS-1 exhibits an amorphous sheet structure with a smooth surface, comprising five distinct glycosidic bonds in its repeating units. The animal experiments showed that EPS-1 might alleviate dextran sulfate sodium-induced colitis by decreasing damage to the intestinal mucosa, intestinal barrier, and inflammatory factor levels, restoring short-chain fatty acids levels, and keeping the balance of intestinal flora. Our findings indicated that EPS-1, which is produced in situ during yogurt fermentation, holds promising potential for the prevention and management of colitis.

Abstract Red ginseng has been used in traditional medicine for centuries in Asia. In this study, we evaluated four types of red ginseng grown in different areas (Chinese red ginseng, Korean red ginseng A, Korean red ginseng B, and Korean red ginseng C) for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene (B(a)P) in A/J mice and found that Korean red ginseng B was the most effective at lowering the tumor load among the four red ginseng varieties. Moreover, we analyzed the levels of various ginsenosides (Rg1, Re, Rc, Rb2, Rb3, Rb1, Rh1, Rd, Rg3, Rh2, F1, Rk1, and Rg5) in four kinds of red ginseng extract and found that Korean red ginseng B had the highest level of ginsenoside Rg3 (G-Rg3), which suggested that G-Rg3 may play an important role in its therapeutic efficacy. This work revealed that the bioavailability of G-Rg3 was relatively poor. However, when G-Rg3 was coadministered with verapamil, a P-glycoprotein inhibitor, the G-Rg3 efflux in Caco-2 cells was lowered, the small intestinal absorption rate of G-Rg3 in the rat models was increased, the concentration levels of G-Rg3 were elevated in the intestine and plasma, and its tumor-preventive abilities in the tumorigenesis rat model induced by B(a)P were also augmented. We also found that G-Rg3 reduced B(a)P-induced cytotoxicity and DNA adduct formation in human lung cells and rescued phase II enzyme expression and activity through Nrf2 pathways, which may be the potential mechanisms underlying the inhibitory effects of G-Rg3 on lung tumorigenesis. Our study showed a potentially vital role of G-Rg3 in targeting lung tumors in murine models. The oral bioavailability of this ginsenoside was augmented by targeting P-glycoprotein, which allowed the molecule to exert its anticancer effects.

The effects of tempering process on the cryogenic impact toughness of 13Cr4NiMo martensitic stainless steel (13-4MSS) were investigated by experiments and crystal plasticity finite element modeling (CPFEM). The tempering structure mainly includes tempered martensite lath, reversed austenite and M23C6 carbide. The tempered martensite lath is refined by the tiny new martensite transformed by reversed austenite, and the refinement degree increases with the tempering temperature. The nucleation of reversed austenite depends on the new martensite and carbide generated during tempering, and more reversed austenite is obtained by double tempering. The cryogenic impact toughness of the material changes nonlinearly with the increase of tempering temperature. It indicates that fine martensitic lath and inverse austenite are beneficial to improve the cryogenic impact toughness of the material, while carbide particles play the opposite role. The results of CPFEM show that reversed austenite coordinates the impact force of the surrounding martensite through large plastic deformation, and eases the stress concentration. Reversed austenite even occurs DIMT behavior under large plastic deformation to further reduce the stress concentration and prevent the initiation and propagation of cracks. As a hard particle, carbide causes the stress concentration, leading to cracks initiation and propagation along the martensite boundary.

Abstract Background Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study. Results Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8+ T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4+ CD28null T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2- SPP1+ foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses. Conclusions We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies.

Aim: We herein present our clinical experience in laparoscopic surgery for gallbladder perforation (GBP). Materials and Methods: Retrospective analysis was performed on the clinical data of 44 patients who diagnosed with GBP from January 2015 to November 2020. Results: The mean age of the 44 patients was 64.0 years and the female-to-male ratio was 20:24. The most common type of GBP was Type II, followed by Type I and Type III (31:9:4). 72.7% of the patients were diagnosed with GBP at the time of surgery. Laparoscopic surgery was performed for 38 (86.4%) patients, with a conversion rate of 13.2%. The mean length of hospital stays was 7.8 days. The mortality and morbidity rates were 2.3% and 11.4%, respectively. Conclusions: Pre-operative diagnosis of GBP is difficult. Laparoscopic surgery is safe, feasible and effective for patients with GBP.

Abstract Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible “off-the-shelf” cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2Mnull), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound β2m-HLA-G1 fusion proteins (B2MmHLAG), and ectopic expression of soluble and secreted β2m-HLA-G5 fusion proteins in B2MmHLAG hPSCs (B2Mm/sHLAG) in the most widely used WA09 human embryonic stem cells. Our results showed that hypoimmunogenic hPSCs with variable expression patterns of HLA molecules and immune compromising spectrums retained their normal self-renewal capacity and three-germ-layer differentiation potency. More importantly, as exemplified by neurons, cardiomyocytes and hepatocytes, hypoimmunogenic hPSC-derived tissue cells were fully functional as of their morphology, electrophysiological properties, macromolecule transportation and metabolic regulation. Our findings thus indicate that engineered hypoimmunogenic hPSCs hold great promise of serving as an unlimited universal cell source for cell therapeutics.

In this paper, we investigate two types of the conditional strong law of large numbers with a new notion of conditionally independent random variables under G-expectation which are related to the symmetry G-function. Our limit theorem demonstrates that the cluster points of empirical averages fall within the bounds of the lower and upper conditional expectations with lower probability one. Moreover, for conditionally independent random variables with identical conditional distributions, we show the existence of two cluster points of empirical averages that correspond to the essential minimum and essential maximum expectations, respectively, with G-capacity one.

This study introduces a novel deep learning network that integrates a single-layer bidirectional long short-term memory (Bi-LSTM) network with a coding layer to analyze the hot deformation behavior of various alloys. The single-layer Bi-LSTM model adeptly predicts experimental stress–strain curves obtained under different deformation temperatures and strain rates, demonstrating superior effectiveness and excellent performance in modeling hot deformation behaviors of the FGH98 nickel-based alloy and TiAl intermetallic alloy. The present model achieves the coefficient of determination of 0.9051 for FGH98 and 0.9307 for TiAl alloys, whereas the corresponding values of 0.8105 and 0.8356 are obtained by the conventional strain-compensated Sellars constitutive equation (SCS model). Additionally, the mean absolute percentage error of the single-layer Bi-LSTM model are 11.37% for FGH98 and 7.16% for TiAl alloys, while the SCS model gains the corresponding error of 15.29% and 17.01%. These results show that the present model has enhances the predictive accuracy exceeding 10% for both FGH98 and TiAl alloys over the SCS model. Consequently, the proposed single-layer Bi-LSTM model provides substantial potential for optimizing manufacturing processes and improving material properties.