Multi-Level Structural Enhancement Mechanism of the Excellent Mechanical Properties of Dung Beetle Leg Joint.

The multi-level structure is a strategy to enhance the mechanical properties of dung beetle leg joints. Under external loads, the microstructure facilitates energy dissipation and prevents crack extension. The macrostructure aids in transferring the load to more reliable parts. The connection established by the two hemispheres is present in the dung beetle leg joint. The micron-layered and nanoscale crystal structures further constitute the leg joint with excellent mechanical properties. The maximum compression fracture force is ≈101000 times the weight of the leg. Here, the structural design within the dung beetle leg joints and reveal the resulting mechanical response and enhancement mechanisms is determined. A series of beetle leg joints where the macrostructure and microstructure of the dung beetle leg provide mechanical strength at critical strains while avoiding catastrophic failure by transferring the load from the joint to the exoskeleton of the femur is highlighted. Nanocrystalline structures and fiber layers contribute to crack propagation of the exoskeleton. Based on this, the bionic joint with multi-level structures using resin and conducted a series of tests to verify their effectiveness is prepared. This study provides a new idea for designing and optimizing high-load joints in engineering.

Structural and functional analyses of viral H2 protein of the vaccinia virus entry fusion complex.

IMPORTANCE: Vaccinia virus infection requires virus-cell membrane fusion to complete entry during endocytosis; however, it contains a large viral fusion protein complex of 11 viral proteins that share no structure or sequence homology to all the known viral fusion proteins, including type I, II, and III fusion proteins. It is thus very challenging to investigate how the vaccinia fusion complex works to trigger membrane fusion with host cells. In this study, we crystallized the ectodomain of vaccinia H2 protein, one component of the viral fusion complex. Furthermore, we performed a series of mutational, biochemical, and molecular analyses and identified two surface loops containing 170LGYSG174 and 125RRGTGDAW132 as the A28-binding region. We also showed that residues in the N-terminal helical region (amino acids 51-90) are also important for H2 function.

Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine.

In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigated the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the "Knob-into-Hole" technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, elicited remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.

Spatiotemporal Evolution and Spatial Analysis of Ecological Environmental Quality in the Longyangxia to Lijiaxia Basin in China Based on GEE.

The upper reaches of the Yellow River are critical ecological barriers within the Yellow River Basin (YRB) that are crucial for source conservation. However, environmental challenges in this area, from Longyangxia to Lijiaxia, have emerged in recent years. To assess the ecological environment quality (EEQ) evolution from 1991 to 2021, we utilized remote sensing ecological indices (RSEIs) on the Google Earth Engine (GEE) platform. Spatial autocorrelation and heterogeneity impacting EEQ changes were examined. The results of this study show that the mean value of the RSEIs fluctuated over time (1991: 0.70, 1996: 0.77, 2001: 0.67, 2006: 0.71, 2011: 0.68, 2016: 0.65, and 2021: 0.66) showing an upward, downward, and then upward trend. The mean values of the overall RSEI are all at 0.65 and above. Most regions showed no significant EEQ change during 1991-2021 (68.59%, 59.23%, and 55.78%, respectively). Global Moran's I values (1991-2021) ranged from 0.627 to 0.412, indicating significant positive correlation between EEQ and spatial clustering, and the LISA clustering map (1991-2021) shows that the area near Longyangxia Reservoir shows a pattern of aggregation, dispersion, and then aggregation again. The factor detection results showed that heat was the most influential factor, and the interaction detection results showed that greenness and heat had a significant effect on regional ecosystem distribution. Our study integrates spatial autocorrelation and spatial heterogeneity and combines them with reality to provide an in-depth discussion and analysis of the Longyangxia to Lijiaxia Basin. These findings offer guidance for ecological governance, vegetation restoration, monitoring, and safeguarding the upper Yellow River's ecological integrity.

Effectiveness of home-based cardiac telerehabilitation based on wearable ECG or heart rate monitoring devices in patients with heart disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

Interplay between H3K36me3, methyltransferase SETD2, and mismatch recognition protein MutSα facilitates processing of oxidative DNA damage in human cells.

Oxidative DNA damage contributes to aging and the pathogenesis of numerous human diseases including cancer. 8-hydroxyguanine (8-oxoG) is the major product of oxidative DNA lesions. Although OGG1-mediated base excision repair is the primary mechanism for 8-oxoG removal, DNA mismatch repair has also been implicated in processing oxidative DNA damage. However, the mechanism of the latter is not fully understood. Here, we treated human cells defective in various 8-oxoG repair factors with H2O2 and performed biochemical, live cell imaging, and chromatin immunoprecipitation sequencing analyses to determine their response to the treatment. We show that the mismatch repair processing of oxidative DNA damage involves cohesive interactions between mismatch recognition protein MutSα, histone mark H3K36me3, and H3K36 trimethyltransferase SETD2, which activates the ATM DNA damage signaling pathway. We found that cells depleted of MutSα or SETD2 accumulate 8-oxoG adducts and fail to trigger H2O2-induced ATM activation. Furthermore, we show that SETD2 physically interacts with both MutSα and ATM, which suggests a role for SETD2 in transducing DNA damage signals from lesion-bound MutSα to ATM. Consistently, MutSα and SETD2 are highly coenriched at oxidative damage sites. The data presented here support a model wherein MutSα, SETD2, ATM, and H3K36me3 constitute a positive feedback loop to help cells cope with oxidative DNA damage.

scCancer: a package for automated processing of single-cell RNA-seq data in cancer.

Molecular heterogeneities and complex microenvironments bring great challenges for cancer diagnosis and treatment. Recent advances in single-cell RNA-sequencing (scRNA-seq) technology make it possible to study cancer cell heterogeneities and microenvironments at single-cell transcriptomic level. Here, we develop an R package named scCancer, which focuses on processing and analyzing scRNA-seq data for cancer research. Except basic data processing steps, this package takes several special considerations for cancer-specific features. Firstly, the package introduced comprehensive quality control metrics. Secondly, it used a data-driven machine learning algorithm to accurately identify major cancer microenvironment cell populations. Thirdly, it estimated a malignancy score to classify malignant (cancerous) and non-malignant cells. Then, it analyzed intra-tumor heterogeneities by key cellular phenotypes (such as cell cycle and stemness), gene signatures and cell-cell interactions. Besides, it provided multi-sample data integration analysis with different batch-effect correction strategies. Finally, user-friendly graphic reports were generated for all the analyses. By testing on 56 samples with 433 405 cells in total, we demonstrated its good performance. The package is available at: http://lifeome.net/software/sccancer/.

One-stage efficacy of single tract minimally invasive ECIRS in the improved prone frog split-leg position for staghorn stones.

OBJECTIVE: To explore the feasibility, safety, and effectiveness of single tract minimally invasive endoscopic combined intrarenal surgery (stmECIRS) in the improved prone frog split-leg position for staghorn stones. METHOD: A total of 83 patients with staghorn stones were retrospectively reviewed between January 2018 and June 2021. According to surgical procedure and position, patients were divided into a group of single tract minimally invasive percutaneous nephroscopy (stmPNL) in the prone position and a group of stmECIRS in the improved prone frog split-leg position (turned to the prone position after preset the flexible ureteroscope sheath in lithotomy position, meanwhile, bend both hips and knees to be frog abduction). Demographic characteristics, laboratory tests, stone characters, surgical information, stone-free rate (SFR), and perioperative complications were observed and analyzed. RESULTS: There were no significant differences in demographic characteristics, changes level of Scr and Hb, stone size, radiation density, length of hospital stay, and operation time between the two groups. One-stage SFR in the stmECIRS group was significantly higher than that in the stmPNL group (84.4% vs. 57.9%) (P = 0.007), only 2 patients required blood transfusion after surgery (P = 0.862), and other postoperative complications were not statistically significant (P = 0.345). CONCLUSIONS: StmECIRS in improved prone frog split-leg position has a higher one-stage SFR than stmPNL for staghorn renal stones, and without complications increased, which is a safe, efficient and feasible treatment.

Clinical Features of Spontaneous Remission in the Classic Fever of Unknown Origin: A Retrospective Study.

Objective To summarize the clinical features of spontaneous remission in classic fever of unknown origin (FUO). Methods Medical records of 121 patients diagnosed with FUO at admission in Peking Union Medical College Hospital between January 2018 and June 2018 were reviewed retrospectively. Patients who were discharged without etiological diagnoses were followed for 2 years. The clinical features and outcomes of these patients were summarized. Multivariate logistic regression was used to analyze related factors of spontaneous remission of FUO. Results After excluding 2 patients who lost to follow-up, the etiology of 119 FUO patients were as follows: infectious diseases in 30 (25.2%) cases, connective tissue diseases in 28 (23.5%) cases, tumor diseases in 8 (6.7%) cases, other diseases in 6 (5.0%) cases, and unknown diagnoses in 47 (39.5%) cases. Totally, 41 patients experienced spontaneous remission of fever (the median time from onset to remission was 9 weeks, ranging from 4 to 39 weeks). In patients with spontaneous remission in FUO, lymphadenopathy was less common clinical manifestation, the levels of inflammatory markers including leukocyte count, neutrophil count, neutrophil ratio, C-reactive protein, and ferritin were lower, and the proportion of CD8 positive T lymphocytes expressing CD38 was lower. Multivariate logistic regression analysis of factors with a P-value < 0.05 in univariate analysis shown that white blood cell count (OR: 0.545, 95%CI: 0.306-0.971, P = 0.039), neutrophil count (OR: 2.074, 95%CI: 1.004-4.284, P = 0.049), and proportion of neutrophils (OR: 0.928, 95%CI: 0.871-0.990, P = 0.022) were independent significant factors associated with spontaneous remission in FUO. Conclusions This study suggested that most patients discharged with undiagnosed classic FUO would remit spontaneously. Thus, for patients with stable clinical conditions, follow-up and observation could be the best choice. Patients with lower level of some inflammatory factors may have a high likelihood of spontaneous remission in classic FUO.

Fused Lateral Clitoral Hood and Labia Minora: New Classification Based on Anatomic Variation of the Clitoral Hood-Labia Minora Complex and Simple Surgical Management.

BACKGROUND: Existing classifications of the clitoral hood-labia minora complex (CLC) have neglected its integrity and anatomic variation, resulting in failure to optimize approaches tailored to individuals. OBJECTIVES: The aim of this study was to present a new classification system for comprehensive evaluation of variations of the CLC and to introduce a simple surgical approach for the fused type. METHODS: Anatomic variations of the CLC were classified into 3 types: isolated labia minora or lateral clitoral hood hypertrophy (Type 1); conventional combined hypertrophy (Type 2); and fused lateral clitoral hood and labia minora (Type 3). A modified procedure for the fused type was performed in 4 steps: the anterior border of labia minora was defined first, then the hypertrophic lateral clitoral hood and labia minora were each removed separately, and finally the junction region was trimmed. Satisfaction questionnaires were administered during follow-ups. RESULTS: Among all 301 patients (602 sides), Type 2 was the most common variation (285 sides, 47.3%). Type 3 variations in 67 patients (105 sides, 17.5%) were identified, and 77.6% of these patients answered the questionnaires 3 months after surgery. For patients with type 3 variations, the satisfaction rate in the 4-step excision group was 91.7%, which was significantly higher than that in the wedge excision group (56.3%) (P = 0.01). The complication rate of the 4-step excision was 2.5%. CONCLUSIONS: Preoperative evaluation based on the new classification facilitated recognition of variations of the CLC, especially of the fused type. The 4-step excision is a simple, effective, and safe approach to treat the fused variation with high satisfaction.

Developing a Decision-Aid Website for Breast Cancer Surgery: An Action Research Approach.

BACKGROUND: Patients with early-stage breast cancer have numerous options when choosing the type of breast surgery method to be applied. Each of these options lead to a similar long-term survival rate, but result in significant differences in appearance, function, cost, recurrence rate, and various other relevant considerations. However, the time available for detailed communication with each patient is often limited in clinics, which puts these women under great psychological stress and can hinder their surgery-related decision making. OBJECTIVE: The objective of this study was to develop a multipurpose surgery decision-making website providing medical information, psychological support, and decision-related simulation for women during breast cancer surgery-related decision making. METHODS: Using the 4 steps of action research, which involve multigroup teamwork via regular team meetings, the following were performed: (1) Planning: searching, analyzing, and evaluating health websites to consensually decide the major infrastructure; (2) Action: work was performed simultaneously in 4 groups, which consisted of medical information collection and editing, patient interviews and data extraction, webpage content design, and programming to create or host the website; (3) Evaluation: the website was tested by clinical experts and focus groups of former breast cancer patients to assess its effectiveness and pinpoint appropriate improvements; and (4) Reflection: constant dialogue was conducted between the various participants at each step, which was used as the foundation and motivation of next plan-action-evaluation-reflection circle. RESULTS: Using the action research approach, we completed the development of our website, which includes the following: (1) "Woman's Voice"-an animated comic depicting the story of a female breast cancer patient with interspersed questions for the users that will help them better empathize with the experience; (2) "Cancer Information Treasure House"-providing breast cancer surgery-related information through text, tables, pictures and a presentation video; (3) "Decision-making Simulator"-helping patients think through and check the pros and cons of the different surgical options via visual-based interactions including "Stairs Climbing" and "Fruit of Hope"; and (4) "Recommended Links"-providing reliable websites for further reference. Additionally, we have further improved the website based on the feedback received from postsurgery breast cancer patients and clinicians. We hope to continue improving to better meet both the patients' and health providers' needs and become a practical decision-making aid for patients undergoing breast cancer surgery. CONCLUSIONS: We have created the first breast cancer surgery decision-making assistance tool in Taiwan using a "Web-based" and multifunctional website design. This site aims to provide health care knowledge, psychological healing, and emotional support functions, as well as decision-making capability enhancement simulations. We look forward to assisting breast cancer patients in their decision-making process and expect our website to increase patient's autonomy and improve their communication with clinicians.

NHC-Catalyzed Chemoselective Reactions of Enals and Aminobenzaldehydes for Access to Chiral Dihydroquinolines.

An N-heterocyclic carbene (NHC)-catalyzed reaction between α-bromoenals and 2-aminoaldehydes has been developed. Key steps include chemoselective reaction of the NHC catalyst with one of the aldehyde substrates (the bromoenal) to eventually generate an α,ß-unsaturated acylazolium intermediate. Addition of the nitrogen atom of aminoaldehyde to the unsaturated azolium ester intermediate followed by intramolecular aldol reaction, ß-lactone formation, and decarboxylation leads to chiral dihydroquinolines with high optical purity. The dihydroquinoline products, which are quickly prepared by using this method, can be readily transformed into a diverse set of functional molecules such as pyridines and chiral piperidines.

Characteristics of CT Perfusion Parameters of Focal Pancreatic Lesions and Data Comparison of Different Algorithms.

Objective To characterize the CT perfusion parameters of focal pancreatic lesions including pancreatic cancers (PACs) and pancreatic neuroendocrine tumors (pNETs),estimate the confirmity and fungibility of parameters obtained from Deconvolution and Maximum slope+Patlak.Methods From December 2015 to November 2016,22 patients with PACs and 22 patients with pNETs(37 lesions confirmed by surgery and biopsy)underwent preoperative whole-pancreas CT perfusion in our center. The volume perfusion CT of the entire pancreas was performed at 80 kV and 100 mA,using 28 consecutive volume measurements and intravenous injection of 45 ml of iodinated contrast and saline at a flow rate of 5 ml/s. One experienced radiologists measured and recorded the CT perfusion parameters on Siemens post-processing workstation using two mathematical methods:Maximum slope+Patlak analysis versus Deconvolution method.ResultsWilcoxon matched-pairs test revealed significant difference between both pairs of the perfusion measurements by the two methods,PACs(BFM vs. BFD,Z=-3.263,P=0.001;BVD vs. BVP,Z=-3.978,P=0.000); pNETs(BFM vs. BFD,Z=-5.212,P=0.000;BVD vs. BVP,Z=-2.633,P=0.008). Spearman's correlation coefficient showed both pairs of perfusion measurements significantly correlated with each other in PACs (BFM vs. BFD,r=0.845,P=0.000;BVD vs. BVP,r=0.964,P=0.000) and pNETs(BFM vs. BFD,r=0.759,P=0.000),BVD vs. BVP,r=0.683,P=0.000). Geometric mean BFM/BFD ratio in PACs was 0.77 (range:0.61-0.99),while geometric mean BVD/BVP ratio was 1.42 (range:1.13-1.79),within 95% limits of agreement. Geometric mean BFM/BFD ratio in pNETs was 0.66 (range:0.51-0.86),while geometric mean BVD/BVP ratio was 1.15 (range:0.88-1.50),within 95% limits of agreement. Conclusion sSignificantly different CT perfusion values of blood flow and blood volume were obtained by Deconvolution-based and Maximum slope+Patlak-based algorithms in the pNETs and PACs. They correlated significantly with each other. Two perfusion-measuring algorithms are interchangeable because the ranges of the conversion factors are narrow.

Taohong Siwu decoction reduces acute myocardial ischemia-reperfusion injury by promoting autophagy to inhibit pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu decoction (TSD) is a classic traditional Chinese medicine (TCM) prescription used to promote the blood circulation and alleviate blood stasis. TSD consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. Studies on the effects of TSD on myocardial ischemia-reperfusion injury (MIRI) from the perspective of autophagy and pyroptosis have not been reported. AIM OF THE STUDY: Investigate the effect of TSD on MIRI and explore the underlying mechanisms. MATERIALS AND METHODS: We searched the main components and corresponding potential targets of TSD on The Pharmacology of Traditional Chinese Medicine Systems database for target prediction. We identified targets for MIRI on Online Mendelian Inheritance in Man and GeneCards databases. The intersection of the compound target and disease target was obtained and a protein-protein interaction network constructed. We undertook enrichment analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The results of network pharmacology were verified by in vivo experiments in mice. RESULTS: In mice, TSD significantly reduced the volume of the myocardial infarct, significantly reduced serum levels of cardiac troponin-nI (CTnI), creatine kinase-myocardial band (CK-MB), malonaldehyde (MDA), interleukin (IL)-6, increased the activity of superoxide dismutase (SOD) and IL-10 level, reduced the level of pyroptosis in myocardial tissue, increased the number of autophagosomes, and significantly reduced the fluorescence intensity of apoptosis-associated speck-like protein (ASC), Nod-like receptor protein 3 (NLRP3), and caspase-1. TSD administration increased the protein expression of microtubule-associated protein light chain 3 (LC3), but reduced the protein expression of p62, NLRP3, ASC, caspase-1, cleaved caspase-1, pro-caspase-1, gasdermin D (GSDMD), GSDMD-N-terminal, IL-18, and IL-1ß. Administration of 3-Methyladenin could reverse the effect of TSD in inhibiting inflammation and the release of proinflammatory factors. CONCLUSION: TSD treatment alleviated MIRI by promoting autophagy to suppress activation of the NLRP3 inflammasome and reducing the release of proinflammatory factors.

Identification and validation of new fatty acid metabolism-related mechanisms and biomarkers for erectile dysfunction.

Background: Erectile dysfunction (ED) is a common condition affecting middle-aged and elderly men. Aim: The study sought to investigate differentially expressed fatty acid metabolism-related genes and the molecular mechanisms of ED. Methods: The expression profiles of GSE2457 and GSE31247 were downloaded from the Gene Expression Omnibus database and merged. Differentially expressed genes (DEGs) between ED and normal samples were obtained using the R package limma. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs were conducted using the R package clusterProfiler. Fatty acid metabolism-related DEGs (FAMDEGs) were further identified and analyzed. Machine learning algorithms, including Lasso (least absolute shrinkage and selection operator), support vector machine, and random forest algorithms, were utilized to identify hub FAMDEGs with the ability to predict ED occurrence. Coexpression analysis and gene set enrichment analysis of hub FAMDEGs were performed. Outcome: Fatty acid metabolism-related functions (such as fatty acid metabolism and degradation) may play a vital role in ED. Results: In total, 5 hub FAMDEGs (Aldh2, Eci2, Acat1, Acadl, and Hadha) were identified and found to be differentially expressed between ED and normal samples. Gene set enrichment analysis identified key pathways associated with these genes. The area under the curve values of the 5 hub FAMDEGs for predicting ED occurrence were all >0.8. Clinical Translation: Our results suggest that these 5 key FAMDEGs may serve as biomarkers for the diagnosis and treatment of ED. Strengths and Limitations: The strengths of our study include the use of multiple datasets and machine learning algorithms to identify key FAMDEGs. However, limitations include the lack of validation in animal models and human tissues, as well as research on the mechanisms of these FAMDEGs. Conclusion: Five hub FAMDEGs were identified as potential biomarkers for ED progression. Our work may prove that fatty acid metabolism-related genes are worth further investigation in ED.

A Case of Pulmonary Actinomycosis With Concurrent Gastric Adenocarcinoma in an Older Adult.

Actinomycosis is a chronic granulomatous disease that can affect various parts of the body, including the head and neck, lungs, abdominal and pelvic cavities, and wounds. It is caused by different actinomycetes like Actinomyces sherdii, Actinomyces glasii, Actinomyces cariosa, Actinomyces zurichensis, and Actinomyces europaea. Reported infections caused by actinomycetes include pulmonary actinomycosis, pelvic and abdominal infections, bone or artificial joint infections, endocarditis, complicated urinary tract infections, and soft tissue abscesses. The combination of pulmonary actinomycosis with gastric cancer is exceptionally rare in clinical practice, and the presence of actinomycetal infection alongside tumors in elderly patients poses significant challenges in treatment. This article presents the diagnosis and treatment process of an elderly patient with pulmonary actinomycosis and gastric adenocarcinoma.

ALKBH5-Mediated m6A Modification Drives Apoptosis in Renal Tubular Epithelial Cells by Negatively Regulating MUC1.

Dysregulation of renal tubular epithelial cell (RTEC) apoptosis is one of the critical steps underlying the occurrence and development of nephrolithiasis. Although N6-methyladenosine (m6A) modification has been extensively studied and associated with various pathologic processes, research on its specific role in RTEC injury and apoptosis remains limited. In this study, we found that overexpression of ALKBH5 reduced the level of m6A modification in RTEC cells and notably promoted RTEC apoptosis. Further mechanism studies revealed that ALKBH5 mainly  decreased the m6A level on the mRNA of  Mucin 1 (MUC1) gene in RTECs. Moreover, ALKBH5  impaired the stability of MUC1 mRNA in RTECs, leading to  attenuated expression of MUC1. Finally, we determined that the ALKBH5-MUC1 axis primarily facilitated RTEC apoptosis by regulating the PI3K/Akt signaling pathway. This study revealed the critical role of the ALKBH5-MUC1-PI3K/Akt regulatory system in RTEC apoptosis and provided new therapeutic targets for treating nephrolithiasis.

Polymeric silk fibroin hydrogel as a conductive and multifunctional adhesive for durable skin and epidermal electronics.

Silk fibroin (SF)-based hydrogels are promising multifunctional adhesive candidates for real-world applications in tissue engineering, implantable bioelectronics, artificial muscles, and artificial skin. However, developing conductive SF-based hydrogels that are suitable for the micro-physiological environment and maintain their physical and chemical properties over long periods of use remains challenging. Herein, we developed an ion-conductive SF hydrogel composed of glycidyl methacrylate silk fibroin (SilMA) and bioionic liquid choline acylate (ChoA) polymer chains, together with the modification of acrylated thymine (ThyA) and adenine (AdeA) functional groups. The resulting polymeric ion-conductive SF composite hydrogel demonstrated high bioactivity, strong adhesion strength, good mechanical compliance, and stretchability. The formed hydrogel network of ChoA chains can coordinate with the ionic strength in the micro-physiological environment while maintaining the adaptive coefficient of expansion and stable mechanical properties. These features help to form a stable ion-conducting channel for the hydrogel. Additionally, the hydrogel network modified with AdeA and ThyA, can provide a strong adhesion to the surface of a variety of substrates, including wet tissue through abundant hydrogen bonding. The biocompatible and ionic conductive SF composite hydrogels can be easily prepared and incorporated into flexible skin or epidermal sensing devices. Therefore, our polymeric SF-based hydrogel has great potential and wide application to be an important component of many flexible electronic devices for personalized healthcare.

Single-cell metabolite profiling enables information-rich classification of lymphocyte types and subtypes.

Lymphocytes play crucial roles in the human immune system; however, detailed metabolite characteristics need to be further investigated. Herein, we propose a lymphocyte classification method based on metabolite profiling at the single-cell level. The percentages of different lymphocyte types were calculated with a low margin of error, confirming that the metabolites could serve as a basis for lymphocyte classification. Furthermore, we analyzed the CD4/CD8 ratio in human peripheral blood to verify the feasibility of this method for the classification of lymphocyte subtypes. The proposed method is expected to be a potential tool for the clinical diagnosis of lymphocyte-related diseases.

Study of the influence of macro-structure and micro-structure on the mechanical properties of stag beetle upper jaw.

Macrostructural control of stress distribution and microstructural influence on crack propagation is one of the strategies for obtaining high mechanical properties in stag beetle upper jaws. The maximum bending fracture force of the stag beetle upper jaw is approximately 154, 000 times the weight of the upper jaw. Here, we explore the macro and micro-structural characteristics of two stag beetle upper jaws and reveal the resulting differences in mechanical properties and enhancement mechanisms. At the macroscopic level, the elliptic and triangular cross-sections of the upper jaw of the two species of stag beetles have significant effects on the formation of cracks. The crack generated by the upper jaws with a triangular section grows slowly and deflects easily. At the microscopic level, the upper jaw of the two species is a chitin cross-layered structure, but the difference between the two adjacent fiber layers at 45° and 50° leads to different deflection paths of the cracks on the exoskeleton. The mechanical properties of the upper jaw of the two species of stag beetle were significantly different due to the interaction of macro-structure and micro-structure. In addition, a series of bionic samples with different cross-section geometries and different fiber cross angles were designed, and mechanical tests were carried out according to the macro-structure and micro-structure characteristics of the stag beetle upper jaw. The effects of cross-section geometry and fiber cross angle on the mechanical properties of bionic samples are compared and analyzed. This study provides new ideas for designing and optimizing highly loaded components in engineering. STATEMENT OF SIGNIFICANCE: The upper jaw of the stag beetle is composed of a complex arrangement of chitin and protein fibers, providing both rigidity and flexibility. This structure is designed to withstand various mechanical stresses, including impacts and bending forces, encountered during its burrowing activities and interactions with its environment. The study of the upper jaw of the stag beetle can provide an efficient structural design for engineering components that are subjected to high loads. Understanding the relationship between structure and mechanical properties in the stag beetle upper jaw holds significant implications for biomimetic design and engineering.