scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

Nutrition, phytochemical profiling, in vitro biological activities, and in silico studies of South Chinese white pitaya (Hylocereus undatus).

Background: White pitaya, a popular tropical fruit, is known for its high nutritional value. It is commercially cultivated worldwide for its potential use in the food and pharmaceutical industries. This study aims to assess the nutritional and phytochemical contents and biological potential of the South Chinese White Pitaya (SCWP) peel, flesh, and seed extracts. Methods: Extract fractions with increasing polarity (ethyl acetate < acetone < ethanol < methanol < aqueous) were prepared. Antibacterial potential was tested against multidrug-resistant (MDR) bacteria, and antioxidant activity was determined using, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assays, and cytotoxic activity against human keratinocyte cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Pharmacological screening and molecular docking simulations were conducted to identify potential antibacterial compounds with druggable characteristics. Molecular dynamics simulation (MDS) was employed to validate the binding stability of the promising ligand-protein complexes. Results: All parts of the fruit exhibited a substantial amount of crucial nutrients (minerals, sugars, proteins, vitamins, and fatty acids). The ethanol (ET) and acetone (AC) fractions of all samples demonstrated notable inhibitory effects against tested MDR bacteria, with MIC50 ranges of 74-925 µg/mL. Both ET and AC fractions also displayed remarkable antioxidant activity, with MIC50 ranges of 3-39 µg/mL. Cytotoxicity assays on HaCaT cells revealed no adverse effects from the crude extract fractions. LC-MS/MS analyses identified a diverse array of compounds, known and unknown, with antibacterial and antioxidant activities. Molecular docking simulations and pharmacological property screening highlighted two active compounds, baicalein (BCN) and lenticin (LTN), showing strong binding affinity with selected target proteins and adhering to pharmacological parameters. MDS indicated a stable interaction between the ligands (BCN and LTN) and the receptor proteins over a 100-ns simulation period. Conclusion: Our study provides essential information on the nutritional profile and pharmacological potential of the peel, flesh, and seeds of SCWP. Furthermore, our findings contribute to the identification of novel antioxidants and antibacterial agents that could be capable of overcoming the resistance barrier posed by MDR bacteria.

Artificial Intelligence (AI)-driven dental education: Exploring the role of chatbots in a clinical learning environment.

STATEMENT OF PROBLEM: Despite their widespread use in various educational contexts, the integration of chatbots into dental clinical education has not been thoroughly investigated. The noted discrepancy signifies a lack of understanding of how chatbots could enhance the personalized and interactive learning experiences of predoctoral dental students. PURPOSE: The purpose of this study was to evaluate the awareness and perceptions of artificial intelligence (AI) technology, interaction experiences, and concerns about a custom-developed chatbot (CB) intervention in the clinical education of predoctoral dental students at the University of Illinois Chicago, College of Dentistry (UIC-COD) compared with the traditional Blackboard (BB) online platform. MATERIAL AND METHODS: Eligible participants (n=86) providing verbal consent were allocated via the random block method into BB (n=43) and CB (n=43) groups and asked to engage with their designated platforms for 10 to 15 minutes by focusing on clinical inquiries in a predoctoral implant clinic and supported by a list of 35 typical questions. After the interaction, participants responded on a 5-point Likert scale to a 19-item survey probing AI awareness, platform engagement, and technological concerns. Survey data were anonymized and analyzed using descriptive, inferential statistics and nonparametric Mann-Whitney U tests to compare interventions. The Bonferroni correction for multiple comparisons was performed (α=.0045). RESULTS: Neither the BB or CB group showed any difference in their awareness and perception of AI technology. The CB group demonstrated improved timeliness (P<.001), more interaction (P<.001), reduced faculty workload (P=.001), enhanced receptiveness (P=.002), and less anxiety (P<.001) and was more satisfied (P<.001) when compared with the BB group. However, concerns regarding the potential for incorrect information (P=.003) were more pronounced in the CB group. CONCLUSIONS: The integration of chatbot technology into dental clinical education significantly enhanced learning and student engagement, highlighting the potential for future technological enrichment of the educational landscape.

Uncovering Potentially Therapeutic Phytochemicals, In silico Analysis, and Biological Assessment of South-Chinese Red Dragon Fruit (Hylocereus polyrhizus).

Red dragon fruit is gaining popularity globally due to its nutritional value and bioactive components. The study aimed to assess the phytochemical, nutritional composition, antioxidant, antibacterial, and cytotoxic properties of extracts from the South Chinese red dragon fruit peel, flesh, and seeds. Extract fractions with increasing polarity (ethyl acetate

scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.

Formation process of extension knee joint contracture following external immobilization in rats.

BACKGROUND: Current research lacks a model of knee extension contracture in rats. AIM: To elucidate the formation process of knee extension contracture. METHODS: We developed a rat model using an aluminum external fixator. Sixty male Sprague-Dawley rats with mature bones were divided into the control group (n = 6) and groups that had the left knee immobilized with an aluminum external fixator for 1, 2, and 3 d, and 1, 2, 3, 4, 6, and 8 wk (n = 6 in each group). The passive extension range of motion, histology, and expression of fibrosis-related proteins were compared between the control group and the immobilization groups. RESULTS: Myogenic contracture progressed very quickly during the initial 2 wk of immobilization. After 2 wk, the contracture gradually changed from myogenic to arthrogenic. The arthrogenic contracture progressed slowly during the 1st week, rapidly progressed until the 3rd week, and then showed a steady progression until the 4rd week. Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time. Correspondingly, the level of transforming growth factor beta 1 (TGF-ß1) and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2) in the anterior joint capsule also increased with the immobilization time. Over time, the cross-sectional area of muscle fibers gradually decreased, while the amount of intermuscular collagen and TGF-ß1, p-Smad2, and p-Smad3 was increased. Unexpectedly, the amount of intermuscular collagen and TGF-ß1, p-Smad2, and p-Smad3 was decreased during the late stage of immobilization (6-8 wk). The myogenic contracture was stabilized after 2 wk of immobilization, whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk. CONCLUSION: This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.

Facial Mucosal Level Change Following Maxillary Anterior Single Immediate Tooth Replacement in Extraction Sockets With Facial Bone Wall Defects: A 4- to 15-Year Retrospective Study.

An intact extraction socket has been considered a prerequisite for an immediate implant placement and provisionalization (IIPP) procedure. Recent studies, however, have shown successful outcomes when IIPP was performed in sockets with a facial bone wall defect. This retrospective study evaluated the facial implant mucosal stability following IIPP in extraction sockets with a facial bone wall defect in the esthetic zone. The study included 16 cases in 16 patients who received maxillary anterior single IIPP with contour bone graft (C-BG) and contour connective tissue graft (C-CTG) in compromised extraction sockets (V- or U-shaped defect). After a mean follow-up of 6 years, the implant success rate was 100% (16/16). Minimal and non-statistically significant changes were noted in the facial implant mucosal and marginal bone level. Statistically significant changes were observed in facial implant mucosal thickness gain (2.5 mm [1.8 mm to 3.5 mm]) and midfacial bone sounding reduction (6 mm). Within the confines of this study, IIPP with simultaneous C-BG and C-CTG in fresh extraction sockets exhibiting a V- or U-shaped facial bone wall defect can lead to long-term successful outcomes in terms of mucosal stability, contour bone gain, and marginal bone level stability.

Molecular subtypes based on DNA sensors predict prognosis and tumor immunophenotype in hepatocellular carcinoma.

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

Management of Root Sensitivity following Socket Shield Technique with Anterior Single Immediate Implant Placement and Provisionalization.

Maintaining facial soft tissue contour and inter-implant papilla are challenging for implants in the esthetic zone. To counteract the inevitable hard and soft tissue changes after tooth extraction, the socket shield technique (SST) has been advocated as means to maintain the facial and/or interproximal osseous and gingival architecture. Because SST is a technique-sensitive procedure, various complications related to SST have been reported. This article presents a unique complication after a socket shield procedure and a novel management of the complication. Int J Periodontics Restorative Dent 2023;43:157-165. doi: 10.11607/prd.5426.

Rational design of bimetallic MXene solid solution with High-Performance electrocatalytic N2 reduction.

Electrocatalytic N2 reduction reaction (eNRR) was an effective alternative method for green synthesis of NH3. By combining the first-principal Density functional theory (DFT) calculations and Monte Carlo (MC) simulation, we systematacially investigated 24 types equal-ratio bimetallic MXene solid solution, involving 88 different catalysts. Our focus was on the catalytic performance of these materials in eNRR. The computational result indicate that MoW(3Mo) has high stability, selectivity (93.8 % against the hydrogen evolution reaction (HER)) and activity (UL = -0.26 V), which is significantly better than that of monometal Mo2CO2 and W2CO2. This improvement in catalytic properties is attributed to the unique electronic structure (e.g. d-band center, charge) of bimetallic MXene solid solution. In explicit solvent conditions, the microenvironment of hydrogen bond in aqueous liquid thermodynamically promotes the catalytic property for eNRR and reduce the catalytic property of HER side reaction, but the kinetic barrier is also increased due to the effect of the hydrogen-bond microenvironment on proton migration. Overall, the obtained bimetallic MXene solid solution MoW(3Mo) exhibits excellent catalytic performance in eNRR.

Computational and artificial intelligence-based methods for antibody development.

Due to their high target specificity and binding affinity, therapeutic antibodies are currently the largest class of biotherapeutics. The traditional largely empirical antibody development process is, while mature and robust, cumbersome and has significant limitations. Substantial recent advances in computational and artificial intelligence (AI) technologies are now starting to overcome many of these limitations and are increasingly integrated into development pipelines. Here, we provide an overview of AI methods relevant for antibody development, including databases, computational predictors of antibody properties and structure, and computational antibody design methods with an emphasis on machine learning (ML) models, and the design of complementarity-determining region (CDR) loops, antibody structural components critical for binding.

Effect of Electrical Stimulation on Disuse Muscular Atrophy Induced by Immobilization: Correlation With Upregulation of PERK Signal and Parkin-Mediated Mitophagy.

OBJECTIVES: The aims of the study are to investigate the effect of electrical stimulation on disuse muscular atrophy induced by immobilization (IM) and to explore the role of PERK signal and Parkin-dependent mitophagy in this process. DESIGN: In the first subexperiment, 24 rabbits were divided into four groups, which underwent different periods of IM. In the second subexperiment, 24 rabbits were divided into four groups on average in accordance with different kinds of interventions. To test the time-dependent changes of rectus femoris after IM, and to evaluate the effect of electrical stimulation, the wet weights, cross-sectional area and fat deposition of rectus femoris were assessed in this study, along with the protein levels of atrogin-1, p-PERK, Parkin, and COXIV. RESULTS: The wet weights and cross-sectional area decreased, and the fat deposition increased in rectus femoris after IM, along with the elevated protein levels of atrogin-1, p-PERK, Parkin, and decreased protein levels of COXIV. The above histomorphological and molecular changes can be partially ameliorated by electrical stimulation. CONCLUSIONS: Immobilization of unilateral lower limb could induce rectus femoris atrophy, which can be partially rectified by electrical stimulation. PERK signal and Parkin-mediated mitophagy may be the mechanisms by which electrical stimulation can play a significant role.

Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death / 法医学杂志

OBJECTIVES@#To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death.@*METHODS@#PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis.@*RESULTS@#Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine).@*CONCLUSIONS@#GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.

Pathological Changes and Cause of Death Associated with the Global Novel Coronavirus Disease (COVID-19) / 法医学杂志

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Introduction: Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research. Method: Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay). Furthermore, proteomic analysis was used to search its possible indirect target proteins by comparing the protein expression profiles of C2C12 myotubes under treatment of C26 medium, with or without the presence of carnosol. The signal network between the direct and indirect target proteins of carnosol was then constructed. Results: Our results showed that, Delta-1-pyrroline-5-carboxylate synthase (P5CS) might be the direct target protein of carnosol in myotubes. The influence of carnosol on amino acid metabolism downstream of P5CS was confirmed. Carnosol could upregulate the expression of proteins related to glutathione metabolism, anti-oxidant system, and heat shock response. Knockdown of P5CS could also ameliorate myotube atrophy and further enhance the ameliorating effects of carnosol. Discussion: These results suggested that carnosol might ameliorate cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Management of Root Sensitivity following Socket Shield Technique with Anterior Single Immediate Implant Placement and Provisionalization.

It is challenging for implants in the esthetic zone to maintain the facial soft tissue contour and interimplant papillae. To counteract the inevitable hard and soft tissue changes after tooth extraction, the socket shield technique (SST) has been advocated as means to maintain the facial and/or interproximal osseous and gingival architecture. As SST is a technique-sensitive procedure, various complications related to SST have been reported. This article presents a unique complication after a socket shield procedure and a novel management of the complication.

Summary of the Experiences and Results of Transesophageal Ultrasound-Guided Ventricular Septal Defect and Atrial Septal Defect Closure Operation.

BACKGROUND: Ventricular septal defect (VSD) and atrial septal defect (ASD) are congenital heart diseases. The techniques of transthoracic closure (TC) and percutaneous closure (PC) for the treatment of VSD and ASD have continuously improved and matured. This study aimed to retrospectively analyze the therapeutic effects of TC and PC on VSD and ASD patients. METHODS: We retrospectively reviewed 928 patients (552 VSD and 376 ASD) who had undergone TC or PC guided by transesophageal ultrasound at the Department of Cardiac Macrovascular Surgery of the First Affiliated Hospital of Nanchang University between August 2010 and August 2020. We collected and evaluated the clinical data of the patients, including age, gender, weight, inlet and outlet diameters of defect, and the operation results of TC and PC. Descriptive statistics were used to analyze means and standard deviations (SD), and the Chi-square test was used to evaluate the difference between groups. RESULTS: Among the 928 patients who were treated with the closure operation, there were no casualties, with 907 patients (97.7%) showing successful closure. Among the 552 VSD patients who were treated with TC, 540 showed successful close, while 12 cases required extracorporeal circulation after the failure of TC. Among the 376 patients with ASD, 256 patients were treated with TC, of which 251 were successful, and five were failures, including three shedding cases. In addition, among the 120 patients who were treated with PC, 116 were successful, and four were failures, including two shedding cases. Postoperative follow up for patients with successful closure operations demonstrated that the complications of aortic and tricuspid regurgitation, hydro-pericardium, III° atrioventricular block, shedding of closure umbrella, hemolysis, and thrombosis had not occurred. CONCLUSION: Closure operation of VSD and ASD by esophageal ultrasound has the advantages of lower trauma and blood loss, shorter hospital stay, simple operation, fewer postoperative complications, and significant therapeutic efficacy.

Carnosol attenuated atrophy of C2C12 myotubes induced by tumour-derived exosomal miR-183-5p through inhibiting Smad3 pathway activation and keeping mitochondrial respiration.

Cancer-derived exosomes are involved in the development of cancer cachexia. Carnosol, which exhibited ameliorating effects on cancer cachexia of C26 tumour-bearing mice in our previous study, alleviated atrophy of C2C12 myotubes induced by exosomes of C26 tumour cells in the present study. MiR-183-5p was found to be rich in C26 cells and C26 exosomes, and miR-183-5p mimic could directly induce atrophy of C2C12 myotubes. Carnosol at 5 to 20 µM could dose-dependently ameliorate the myotube atrophy induced by miR-183-5p. Four and a half LIM domain protein 1 (FHL1) was shown to be the direct target of miR-183-5p. Increase in myostatin, p-Smad3, MuRF-1, Atrogin-1, HIF-1α and p-STAT3 and decrease in mitochondrial respiration were also induced by miR-183-5p mimic in C2C12 myotubes. Carnosol could not affect the decrease in FHL-1 and the activation of STAT3 pathway but could significantly alleviate the increase in myostatin, p-Smad3, MuRF-1, Atrogin-1 and the decrease in mitochondrial respiration induced by miR-183-5p. The protective effects of carnosol on myotubes against atrophy of C2C12 myotubes induced by miR-183-5p, based on both its inhibiting effects on MuRF-1 and Atrogin-1-mediated protein degradation and its ability of keeping the mitochondrial respiration, might contribute to its ameliorating effects on cancer cachexia.

A genetic model for in vivo proximity labelling of the mammalian secretome.

Organ functions are highly specialized and interdependent. Secreted factors regulate organ development and mediate homeostasis through serum trafficking and inter-organ communication. Enzyme-catalysed proximity labelling enables the identification of proteins within a specific cellular compartment. Here, we report a BirA*G3 mouse strain that enables CRE-dependent promiscuous biotinylation of proteins trafficking through the endoplasmic reticulum. When broadly activated throughout the mouse, widespread labelling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) proteomics revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, highlighting both conventional and non-conventional secretory processes, and ectodomain shedding. Lower-abundance proteins with hormone-like properties were recovered and validated using orthogonal approaches. Hepatocyte-specific activation of BirA*G3 highlighted liver-specific biotinylated secretome profiles. The BirA*G3 mouse model demonstrates enhanced labelling efficiency and tissue specificity over viral transduction approaches and will facilitate a deeper understanding of secretory protein interplay in development, and in healthy and diseased adult states.