Engineering of bespoke photosensitiser-microbe interfaces for enhanced semi-artificial photosynthesis.

Biohybrid systems for solar fuel production integrate artificial light-harvesting materials with biological catalysts such as microbes. In this perspective, we discuss the rational design of the abiotic-biotic interface in biohybrid systems by reviewing microbes and synthetic light-harvesting materials, as well as presenting various approaches to coupling these two components together. To maximise performance and scalability of such semi-artificial systems, we emphasise that the interfacial design requires consideration of two important aspects: attachment and electron transfer. It is our perspective that rational design of this photosensitiser-microbe interface is required for scalable solar fuel production. The design and assembly of a biohybrid with a well-defined electron transfer pathway allows mechanistic characterisation and optimisation for maximum efficiency. Introduction of additional catalysts to the system can close the redox cycle, omitting the need for sacrificial electron donors. Studies that electronically couple light-harvesters to well-defined biological entities, such as emerging photosensitiser-enzyme hybrids, provide valuable knowledge for the strategic design of whole-cell biohybrids. Exploring the interactions between light-harvesters and redox proteins can guide coupling strategies when translated into larger, more complex microbial systems.

A novel method of swin transformer with time-frequency characteristics for ECG-based arrhythmia detection.

Introduction: Arrhythmia is an important indication of underlying cardiovascular diseases (CVD) and is prevalent worldwide. Accurate diagnosis of arrhythmia is crucial for timely and effective treatment. Electrocardiogram (ECG) plays a key role in the diagnosis of arrhythmia. With the continuous development of deep learning and machine learning processes in the clinical field, ECG processing algorithms have significantly advanced the field with timely and accurate diagnosis of arrhythmia. Methods: In this study, we combined the wavelet time-frequency maps with the novel Swin Transformer deep learning model for the automatic detection of cardiac arrhythmias. In specific practice, we used the MIT-BIH arrhythmia dataset, and to improve the signal quality, we removed the high-frequency noise, artifacts, electromyographic noise and respiratory motion effects in the ECG signals by the wavelet thresholding method; we used the complex Morlet wavelet for the feature extraction, and plotted wavelet time-frequency maps to visualise the time-frequency information of the ECG; we introduced the Swin Transformer model for classification and achieve high classification accuracy of ECG signals through hierarchical construction and self attention mechanism, and combines windowed multi-head self-attention (W-MSA) and shifted window-based multi-head self-attention (SW-MSA) to comprehensively utilise the local and global information. Results: To enhance the confidence of the experimental results, we evaluated the performance using intra-patient and inter-patient paradigm analyses, and the model classification accuracies reached 99.34% and 98.37%, respectively, which are better than the currently available detection methods. Discussion: The results reveal that our proposed method is superior to currently available methods for detecting arrhythmia ECG. This provides a new idea for ECG based arrhythmia diagnosis.

Nobiletin Protects Against Alcoholic Liver Disease in Mice via the BMAL1-AKT-Lipogenesis Pathway.

SCOPE: Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND RESULTS: This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner. CONCLUSION: Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.

Reduced serum CLCF1 levels in hyperthyroidism patients and T3-treated mice.

Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and peripheral mechanisms. Previous studies have shown an association between dysfunction of cardiotrophin-like cytokine factor 1 (CLCF1) and cold-induced sweating syndrome, with recent research also indicating a link between CLCF1 and brown adipose tissue thermogenesis. However, it remains unclear whether CLCF1 and TH have synergistic or antagonistic effects on thermogenesis. This study aims to investigate the influence of thyroid hormone on circulating CLCF1 levels in humans and explore the potential possibilities of thyroid hormone in regulating energy metabolism by modulating Clcf1 in mice. By recruiting hyperthyroid patients and healthy subjects, we observed significantly lower serum CLCF1 levels in hyperthyroid patients compared to healthy subjects, with serum CLCF1 levels independently associated with hyperthyroidism after adjusting for potential confounders. Tissue analysis from mice treated with T3 revealed a decrease in CLCF1 expression in BAT and iWAT of C57BL/6 mice. These findings suggest that TH may play a role in regulating CLCF1 expression in adipose tissue.

Identifying molecular subgroups of patients with preeclampsia through bioinformatics.

Preeclampsia (PE) is a pregnancy-related disorder associated with serious complications. Its molecular mechanisms remain undefined; hence, we aimed to identify molecular subgroups of patients with PE using bioinformatics to aid treatment strategies. R software was used to analyze gene expression data of 130 patients with PE and 138 healthy individuals from the Gene Expression Omnibus database. Patients with PE were divided into two molecular subgroups using the unsupervised clustering learning method. Clinical feature analysis of subgroups using weighted gene co-expression network analysis showed that the patients in subgroup I were primarily characterized by early onset of PE, severe symptoms at disease onset, and induced labor as the main delivery method. Patients in subgroup II primarily exhibited late PE onset, relatively mild symptoms, and natural delivery as the main delivery method. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the significant enrichment of calcium ion channels in subgroup II indicated the potential efficacy of calcium antagonists and magnesium sulfate therapy. In conclusion, the establishment of PE molecular subgroups can aid in diagnosing and treating PE.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

Evolution of the spatiotemporal pattern of China's grain production in the past 20 years and its driving mechanism.

Food security is a goal and means of global sustainable development, and an important component of China's national security. Based on grain production data from 2000 to 2020, 31 provinces (cities, autonomous regions) in China were used as research units to analyze the spatiotemporal differences and driving forces of grain production in China using a combination of local correlation index, center of gravity transfer model, and geographic detector. The results as follows, ① During the research period, China's total grain production showed a decrease followed by an increase, and the yield per unit area of grain showed an increasing trend. Corn has become the "largest staple food" in China; ② During the research period, the focus of China's grain production continued to shift northward, with Heilongjiang, Henan and Shandong provinces becoming the main grain production areas, with Henan being the province where China's grain production center was located. Among the factors affecting grain yield, the effective irrigation area (0.971) has the strongest explanatory power. Finally, countermeasures and suggestions were proposed from five aspects, stabilizing grain production, reducing grain inventory pressure, implementing regional grain security responsibilities, improving grain circulation efficiency, promoting high-quality grain engineering construction, adjusting grain production structure, strictly implementing farmland protection responsibilities, scientifically applying pesticides, fertilizers and other production materials, emphasizing agricultural infrastructure construction and stabilizing the number of agricultural labor force.

The Role of Exerkines in Obesity-Induced Disruption of Mitochondrial Homeostasis in Thermogenic Fat.

There is a notable correlation between mitochondrial homeostasis and metabolic disruption. In this review, we report that obesity-induced disruption of mitochondrial homeostasis adversely affects lipid metabolism, adipocyte differentiation, oxidative capacity, inflammation, insulin sensitivity, and thermogenesis in thermogenic fat. Elevating mitochondrial homeostasis in thermogenic fat emerges as a promising avenue for developing treatments for metabolic diseases, including enhanced mitochondrial function, mitophagy, mitochondrial uncoupling, and mitochondrial biogenesis. The exerkines (e.g., myokines, adipokines, batokines) released during exercise have the potential to ameliorate mitochondrial homeostasis, improve glucose and lipid metabolism, and stimulate fat browning and thermogenesis as a defense against obesity-associated metabolic diseases. This comprehensive review focuses on the manifold benefits of exercise-induced exerkines, particularly emphasizing their influence on mitochondrial homeostasis and fat thermogenesis in the context of metabolic disorders associated with obesity.

A genome-wide association study identifies candidate genes for sleep disturbances in depressed individuals.

OBJECTIVE: This study aimed to identify candidate loci and genes related to sleep disturbances in depressed individuals and clarify the co-occurrence of sleep disturbances and depression from the genetic perspective. METHODS: The study subjects (including 58,256 self-reported depressed individuals and 6,576 participants with PHQ-9 score ≥ 10, respectively) were collected from the UK Biobank, which were determined based on the Patient Health Questionnaire (PHQ-9) and self-reported depression status, respectively. Sleep related traits included chronotype, insomnia, snoring and daytime dozing. Genome-wide association studies (GWASs) of sleep related traits in depressed individuals were conducted by PLINK 2.0 adjusting age, sex, Townsend deprivation index and 10 principal components as covariates. The CAUSALdb database was used to explore the mental traits associated with the candidate genes identified by the GWAS. RESULTS: GWAS detected 15 loci significantly associated with chronotype in the subjects with self-reported depression, such as rs12736689 at RNASEL (P = 1.00 × 10- 09), rs509476 at RGS16 (P = 1.58 × 10- 09) and rs1006751 at RFX4 (P = 1.54 × 10- 08). 9 candidate loci were identified in the subjects with PHQ-9 ≥ 10, of which 2 loci were associated with insomnia such as rs115379847 at EVC2 (P = 3.50 × 10- 08), and 7 loci were associated with daytime dozing, such as rs140876133 at SMYD3 (P = 3.88 × 10- 08) and rs139156969 at ROBO2 (P = 3.58 × 10- 08). Multiple identified genes, such as RNASEL, RGS16, RFX4 and ROBO2 were reported to be associated with chronotype, depression or cognition in previous studies. CONCLUSION: Our study identified several candidate genes related to sleep disturbances in depressed individuals, which provided new clues for understanding the biological mechanism underlying the co-occurrence of depression and sleep disorders.

Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

Application Effects of Individualized Diet Nursing Combined with the Modified Glasgow-Blatchford Scoring System in Upper Gastrointestinal Bleeding.

Background: Upper gastrointestinal bleeding encompasses bleeding arising from esophageal, gastric, duodenal, or pancreaticobiliary lesions above the Treitz ligament. Research indicates a close association between improper diet and upper gastrointestinal bleeding. Objective: This study aims to investigate the application effects of individualized diet nursing combined with the modified Glasgow-Blatchford scoring system in patients with upper gastrointestinal bleeding. Design: A randomized controlled study was conducted. Setting: The study took place at the First Hospital of Hebei Medical University. Participants: From January 2021 to October 2022, 80 patients with upper gastrointestinal bleeding were selected at our hospital. Using a random number table, they were divided into a control group and an observation group, each comprising 40 cases. Interventions: The control group received routine nursing, while the observation group received individualized diet nursing based on the Glasgow-Blatchford score in addition to routine nursing. Primary Outcome Measures: (1) bleeding frequency, hemostasis time, and hospital stay; (2) re-bleeding rate; (3) Glasgow-Blatchford scores; (4) quality of life; and (5) nursing satisfaction. Results: In the observation group, bleeding frequency, hemostasis time, and hospital stay significantly reduced compared to the control (P < .05). Post-nursing, the observation group had a lower re-bleeding rate (χ2=11.25, P < .05). Before nursing, no statistical differences existed in Glasgow-Blatchford and quality of life scores between groups (P > .05). Post-nursing, both groups saw reduced Glasgow-Blatchford scores, more so in the observation group (P < .05). Quality of life scores increased in both, more notably in the observation group (P < .05). Overall nursing satisfaction was higher in the observation group (P < .05). Conclusions: Individualized diet nursing, based on the Glasgow-Blatchford score, improves cure rates and quality of life and warrants promotion.

HA2-FimA DNA Vaccine Treats Experimental Periodontitis.

PURPOSE: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. MATERIALS AND METHODS: The first batch of rats was divided into two groups and immunised with pure water or pVAX1-HA2-FimA at the age of 6, 7, and 9 weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA high-throughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4 weeks. The rats were immunised with pure water, pVAX1-HA2-FimA vaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17 weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). RESULTS: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p < 0.05). Micro-CT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1 group and periodontitis+pure water group (p < 0.05). CONCLUSION: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss.

A gut-derived hormone regulates cholesterol metabolism.

The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.

Exercise Alleviates Aging of Adipose Tissue through Adipokine Regulation.

Adipose tissue undergoes changes with aging, leading to increased adiposity, inflammatory cell infiltration, reduced angiogenesis, heightened oxidative stress, and alterations in its metabolic function. Regular exercise has been recognized as a powerful intervention that can positively influence adipose tissue health and mitigate the effects of aging. However, the molecular mechanisms underlying the benefits of regular exercise on aging adipose tissue function remain poorly understood. Adipokines released through regular exercise play a potential role in mitigating adipose tissue aging, enhancing the metabolism of glucose and lipids, reducing inflammation and fibrosis, and promoting fat browning and thermogenesis. This review comprehensively summarizes the benefits of regular exercise in addressing the age-related decline in adipose tissue function. Utilizing relevant examples of this approach, we address the possibility of designing therapeutic interventions based on these molecular mechanisms.

Identifying novel chemical-related susceptibility genes for five psychiatric disorders through integrating genome-wide association study and tissue-specific 3'aQTL annotation datasets.

The establishment of 3'aQTLs comprehensive database provides an opportunity to help explore the functional interpretation from the genome-wide association study (GWAS) data of psychiatric disorders. In this study, we aim to search novel susceptibility genes, pathways, and related chemicals of five psychiatric disorders via GWAS and 3'aQTLs datasets. The GWAS datasets of five psychiatric disorders were collected from the open platform of Psychiatric Genomics Consortium (PGC, https://www.med.unc.edu/pgc/ ) and iPSYCH ( https://ipsych.dk/ ) (Demontis et al. in Nat Genet 51(1):63-75, 2019; Grove et al. in Nat Genet 51:431-444, 2019; Genomic Dissection of Bipolar Disorder and Schizophrenia in Cell 173: 1705-1715.e1716, 2018; Mullins et al. in Nat Genet 53: 817-829; Howard et al. in Nat Neurosci 22: 343-352, 2019). The 3'untranslated region (3'UTR) alternative polyadenylation (APA) quantitative trait loci (3'aQTLs) summary datasets of 12 brain regions were obtained from another public platform ( https://wlcb.oit.uci.edu/3aQTLatlas/ ) (Cui et al. in Nucleic Acids Res 50: D39-D45, 2022). First, we aligned the GWAS-associated SNPs of psychiatric disorders and datasets of 3'aQTLs, and then, the GWAS-associated 3'aQTLs were identified from the overlap. Second, gene ontology (GO) and pathway analysis was applied to investigate the potential biological functions of matching genes based on the methods provided by MAGMA. Finally, chemical-related gene-set analysis (GSA) was also conducted by MAGMA to explore the potential interaction of GWAS-associated 3'aQTLs and multiple chemicals in the mechanism of psychiatric disorders. A number of susceptibility genes with 3'aQTLs were found to be associated with psychiatric disorders and some of them had brain-region specificity. For schizophrenia (SCZ), HLA-A showed associated with psychiatric disorders in all 12 brain regions, such as cerebellar hemisphere (P = 1.58 × 10-36) and cortex (P = 1.58 × 10-36). GO and pathway analysis identified several associated pathways, such as Phenylpropanoid Metabolic Process (GO:0009698, P = 6.24 × 10-7 for SCZ). Chemical-related GSA detected several chemical-related gene sets associated with psychiatric disorders. For example, gene sets of Ferulic Acid (P = 6.24 × 10-7), Morin (P = 4.47 × 10-2) and Vanillic Acid (P = 6.24 × 10-7) were found to be associated with SCZ. By integrating the functional information from 3'aQTLs, we identified several susceptibility genes and associated pathways especially chemical-related gene sets for five psychiatric disorders. Our results provided new insights to understand the etiology and mechanism of psychiatric disorders.

Enhancing Mechanical Performance of High-Lignin-Filled Polypropylene via Reactive Extrusion.

Polypropylene (PP) is one of the most extensively used commodity plastics. In terms of eco-friendliness, it is worth considering preparing high-lignin-filled PP. This study explores the incorporation of high lignin content, derived from acetic acid lignin (AAL) and Kraft lignin (KL), into PP through twin-screw extrusion and injection molding. The challenge lies in maintaining mechanical performance. A compatibilizer-specifically, maleic anhydride-grafted polypropylene (MAPP)-is employed to enhance lignin-PP compatibility by chemically bonding with lignin and physically associating with the PP phase. Results indicate that KL maintains better dispersity than AAL. Compatibilizers with a high maleic anhydride (MA) level (≥0.8 wt.%) and moderate melt flow index (MFI) in the range of 60-100 g 10 min⁻¹ prove favorable in constructing a reinforced PP/KL network. Optimizing with 40 wt.% lignin content and 10 parts per hundred (pph) of compatibilizer yields blends with mechanical performance comparable to neat PP, exhibiting a notable increase in modulus and heat deflection temperature (HDT). Furthermore, utilizing PP/lignin blends can lead to a 20% reduction in expenses and approximately 40% reduction in PP-induced greenhouse gas (GHG) emissions. This approach not only reduces PP costs but also adds value to lignin utilization in a sustainable and cost-effective manner.

Knee osteoarthritis: A review of animal models and intervention of traditional Chinese medicine.

BACKGROUND: Knee osteoarthritis (KOA) characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults. The pathophysiology of KOA remains poorly understood, as it involves complex mechanisms that result in the same outcome. Consequently, researchers are interested in studying KOA and require appropriate animal models for basic research. Chinese herbal compounds, which consist of multiple herbs with diverse pharmacological properties, possess characteristics such as multicomponent, multipathway, and multitarget effects. The potential benefits in the treatment of KOA continue to attract attention. PURPOSE: This study aims to provide a comprehensive overview of the advantages, limitations, and specific considerations in selecting different species and methods for KOA animal models. This will help researchers make informed decisions when choosing an animal model. METHODS: Online academic databases (e.g., PubMed, Google Scholar, Web of Science, and CNKI) were searched using the search terms "knee osteoarthritis," "animal models," "traditional Chinese medicine," and their combinations, primarily including KOA studies published from 2010 to 2023. RESULTS: Based on literature retrieval, this review provides a comprehensive overview of the methods of establishing KOA animal models; introduces the current status of advantages and disadvantages of various animal models, including mice, rats, rabbits, dogs, and sheep/goats; and presents the current status of methods used to establish KOA animal models. CONCLUSION: This study provides a review of the animal models used in recent KOA research, discusses the common modeling methods, and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Multi scale-aware attention for pyramid convolution network on finger vein recognition.

In recent years, biometrics has been the most popular style of personal identification. The finger vein is an intrinsic and stable trait, and with the ability to detect liveness, it receives academic and industry attention. However, convolution neural networks (CNNs) based finger vein recognition generally can only cover a small input region by using small kernels. Hence, the performance is poor, facing low-quality finger vein images. It is a challenge to effectively use the critical feature of multi-scale for finger veins. In this article, we extract multi-scale features via pyramid convolution. We propose scale attention, namely, the scale-aware attention (SA) module, which enables dynamic adjustment of the weight of each scale to information aggregation. Utilize the complementation of different scale detail features to enhance the discriminativeness of extracted features, thus improving the finger vein recognition performance. In order to verify the present method's efficiency, we carried out experiments on two public data sets and one internal data, and the wide range of experimental results proves the proposed method's effectiveness.

Acetyltransferase P300 Regulates Glucose Metabolic Reprogramming through Catalyzing Succinylation in Lung Cancer.

Aberrant protein post-translational modification is a hallmark of malignant tumors. Lysine succinylation (Ksucc) plays a vital role in cell energy metabolism in various cancers. However, whether succinylation can be catalyzed by acetyltransferase p300 remains unclear. In this study, we unveiled that p300 is a "writer" for succinylation, and p300-mediated Ksucc promotes cell glycometabolism in lung adenocarcinoma (LUAD). Specifically, our succinylome data revealed that EP300 deficiency leads to the systemic reduction of Ksucc, and 79.55% of the p300-succinylated proteins were found in the cytoplasm, which were primarily enriched in the carbohydrate metabolism process. Interestingly, deleting EP300 led to a notable decrease in Ksucc levels on several glycolytic enzymes, especially Phosphoglycerate Kinase 1 (PGK1). Mutation of the succinylated site of PGK1 notably hindered cell glycolysis and lactic acid excretion. Metabolomics in vivo indicated that p300-caused metabolic reprogramming was mainly attributed to the altered carbohydrate metabolism. In addition, 89.35% of LUAD patients exhibited cytoplasmic localization of p300, with higher levels in tumor tissues than adjacent normal tissues. High levels of p300 correlated with advanced tumor stages and poor prognosis of LUAD patients. Briefly, we disclose the activity of p300 to catalyze succinylation, which contributes to cell glucose metabolic reprogramming and malignant progression of lung cancer.

CLCF1 inhibits energy expenditure via suppressing brown fat thermogenesis.

Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis which plays an important role in thermogenesis and energy metabolism. However, the regulatory factors that inhibit BAT activity remain largely unknown. Here, cardiotrophin-like cytokine factor 1 (CLCF1) is identified as a negative regulator of thermogenesis in BAT. Adenovirus-mediated overexpression of CLCF1 in BAT greatly impairs the thermogenic capacity of BAT and reduces the metabolic rate. Consistently, BAT-specific ablation of CLCF1 enhances the BAT function and energy expenditure under both thermoneutral and cold conditions. Mechanistically, adenylate cyclase 3 (ADCY3) is identified as a downstream target of CLCF1 to mediate its role in regulating thermogenesis. Furthermore, CLCF1 is identified to negatively regulate the PERK-ATF4 signaling axis to modulate the transcriptional activity of ADCY3, which activates the PKA substrate phosphorylation. Moreover, CLCF1 deletion in BAT protects the mice against diet-induced obesity by promoting BAT activation and further attenuating impaired glucose and lipid metabolism. Therefore, our results reveal the essential role of CLCF1 in regulating BAT thermogenesis and suggest that inhibiting CLCF1 signaling might be a potential therapeutic strategy for improving obesity-related metabolic disorders.