Progress in the Application of Organoids-On-A-Chip in Diseases.

With the rapid development of the field of life sciences, traditional 2D cell culture and animal models have long been unable to meet the urgent needs of modern biomedical research and new drug development. Establishing a new generation of experimental models and research models is of great significance for deeply understanding human health and disease processes, and developing effective treatment measures. As is well known, long research and development cycles, high risks, and high costs are the "three mountains" facing the development of new drugs today. Organoids and organ-on-chips technology can highly simulate and reproduce the human physiological environment and complex reactions in vitro, greatly improving the accuracy of drug clinical efficacy prediction, reducing drug development costs, and avoiding the defects of drug testing animal models. Therefore, organ-on-chips have enormous potential in medical diagnosis and treatment.

An Integrated Neural Optrode with Modification of Polymer-Carbon Composite Films for Suppression of the Photoelectric Artifacts.

Optogenetics-based integrated photoelectrodes with high spatiotemporal resolution play an important role in studying complex neural activities. However, the photostimulation artifacts caused by the high level of integration and the high impedance of metal recording electrodes still hinder the application of photoelectrodes for optogenetic studies of neural circuits. In this study, a neural optrode fabricated on sapphire GaN material was proposed, and 4 µLEDs and 14 recording microelectrodes were monolithically integrated on a shank. Poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate and multiwalled carbon nanotubes (PEDOT:PSS-MWCNT) and poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT-GO) composite films were deposited on the surface of the recording microelectrode by electrochemical deposition. The results demonstrate that compared with the gold microelectrode, the impedances of both composite films reduced by more than 98%, and the noise amplitudes decreased by 70.73 and 87.15%, respectively, when exposed to light stimulation. Adjusting the high and low levels, we further reduced the noise amplitude by 48.3%. These results indicate that modifying the electrode surface by a polymer composite film can effectively enhance the performance of the microelectrode and further promote the application of the optrode in the field of neuroscience.

Stereoscopic Imaging of Single Molecules at Plasma Membrane of Single Cell Using Photoreduction-Assisted Electrochemistry.

Stereoscopic imaging of single molecules at the plasma membrane of single cell requires spatial resolutions in 3 dimensions (x-y-z) at 10-nm level, which is rarely achieved using most optical super-resolution microscopies. Here, electrochemical stereoscopic microscopy with a detection limit down to a single molecule is achieved using a photoreduction-assisted cycle inside a 20-nm gel electrolyte nanoball at the tip of a nanopipette. On the basis of the electrochemical oxidation of Ru(bpy)3 2+ into Ru(bpy)3 3+ followed by the reduction of Ru(bpy)3 3+ into Ru(bpy)3 2+ by photogenerated isopropanol radicals, a charge of 1.5 fC is obtained from the cycling electron transfers involving one Ru(bpy)3 2+/3+ molecule. By using the nanopipette to scan the cellular membrane modified with Ru(bpy)3 2+-tagged antibody, the morphology of the cell membrane and the distribution of carcinoembryonic antigen (CEA) on the membrane are electrochemically visualized with a spatial resolution of 14 nm. The resultant stereoscopic image reveals more CEA on membrane protrusions, providing direct evidence to support easy access of membrane CEA to intravenous antibodies. The breakthrough in single-molecule electrochemistry at the cellular level leads to the establishment of high-resolution 3-dimensional single-cell electrochemical microscopy, offering an alternative strategy to remedy the imperfection of stereoscopic visualization in optical microscopes.

Prevalence of Chronic Obstructive Pulmonary Disease and Its Associated Risk Factors in Yunnan Province, China: A Population Based Cross-Sectional Study.

Purpose: Chronic obstructive pulmonary disease (COPD) is a significant disease impacting health and quality of life. Yunnan Province, a major tobacco producer, lacks comprehensive COPD studies. The purpose of this study is to describe the epidemic situation of COPD in Yunnan province and explore its influencing factors. Methods: This study is a cross-sectional research conducted in a representative sample of adults aged 20 and older from 13 prefectures and cities in Yunnan Province, China. COPD was diagnosed using post-bronchodilator pulmonary function tests. Demographics were analyzed with descriptive statistics. The influencing factors of COPD were examined by using the multivariate logistic regression models. Results: Our study found that high-risk individuals for COPD accounted for 20.30% of the screened population aged 20 and above, with a COPD prevalence of 27.18% among this high-risk group. Male had a higher prevalence (33.01%) than did female (16.35%; p<0.001 for sex difference). Additionally, the proportion of severe and extremely severe COPD cases in Yunnan Province was higher than the national average and other provinces. After considering the potential confounding variables, male (OR=2.291, 95% CI: 1.584-3.313), age (OR=1.501, 95% CI: 1.338-1.685), underweight (OR=1.747, 95% CI: 1.225-2.491), previous smoking (OR=1.712, 95% CI: 1.182-2.478), passive smoking (OR=1.444, 95% CI: 1.159-1.800), and a history of respiratory system diseases in childhood (OR=2.010, 95% CI: 1.346-3.001) were significantly associated with an increased risk of COPD. Conversely, being overweight (OR=0.636, 95% CI: 0.489-0.828), and residing in high-altitude counties (OR=0.445, 95% CI: 0.263-0.754) were negatively correlated with the risk of COPD. Conclusion: There is significant prevalence of COPD (27.18%) among high-risk population aged 20 and above in Yunnan Province, China. Apart from male, smoking, BMI and other known risk factors for COPD. We found that high-altitude residence had a lower prevalence of COPD. There is no significant difference in COPD prevalence between Han and ethnic minority populations.

Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

Ualign: pushing the limit of template-free retrosynthesis prediction with unsupervised SMILES alignment.

MOTIVATION: Retrosynthesis planning poses a formidable challenge in the organic chemical industry, particularly in pharmaceuticals. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency. RESULTS: This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods. SCIENTIFIC CONTRIBUTION: We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5% (top-5) and 5.4% (top-10) increased accuracy over the strongest baseline.

Rapid identification of various chemical components in Cinnamomi ramulus by UPLC-Q-Orbitrap-MS.

Cinnamomi ramulus (CR) is a common Chinese herbal medicine with a long history. It is often used to treat exogenous wind-cold diseases in clinic, but its chemical compositions remain to be studied. In this study, CR was extracted with 75% ethanol, and UPLC-Q-Orbitrap-MS combined with data post-processing method was used to identify the chemical components in the extract. Through this technology, the components in CR can be separated and accurately identified. A total of 61 compounds were identified, including 14 simple phenylpropanoids, 3 coumarins, 5 lignans, 14 flavonoids, 10 benzoic acids, 8 organic acids, and 7 others. This study confirmed the existence of these compounds in CR and speculated the cleavage pathways of each compound, which enriched the mass spectrometry data and cleavage rules. This study can provide a reference for CR and other research.

A prognostic framework for predicting lung signet ring cell carcinoma via a machine learning based cox proportional hazard model.

PURPOSE: Signet ring cell carcinoma (SRCC) is a rare type of lung cancer. The conventional survival nomogram used to predict lung cancer performs poorly for SRCC. Therefore, a novel nomogram specifically for studying SRCC is highly required. METHODS: Baseline characteristics of lung signet ring cell carcinoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression and random forest analysis were performed on the training group data, respectively. Subsequently, we compared results from these two types of analyses. A nomogram model was developed to predict 1-year, 3-year, and 5-year overall survival (OS) for patients, and receiver operating characteristic (ROC) curves and calibration curves were used to assess the prediction accuracy. Decision curve analysis (DCA) was used to assess the clinical applicability of the proposed model. For treatment modalities, Kaplan-Meier curves were adopted to analyze condition-specific effects. RESULTS: We obtained 731 patients diagnosed with lung signet ring cell carcinoma (LSRCC) in the SEER database and randomized the patients into a training group (551) and a validation group (220) with a ratio of 7:3. Eight factors including age, primary site, T, N, and M.Stage, surgery, chemotherapy, and radiation were included in the nomogram analysis. Results suggested that treatment methods (like surgery, chemotherapy, and radiation) and T-Stage factors had significant prognostic effects. The results of ROC curves, calibration curves, and DCA in the training and validation groups demonstrated that the nomogram we constructed could precisely predict survival and prognosis in LSRCC patients. Through deep verification, we found the constructed model had a high C-index, indicating that the model had a strong predictive power. Further, we found that all surgical interventions had good effects on OS and cancer-specific survival (CSS). The survival curves showed a relatively favorable prognosis for T0 patients overall, regardless of the treatment modality. CONCLUSIONS: Our nomogram is demonstrated to be clinically beneficial for the prognosis of LSRCC patients. The surgical intervention was successful regardless of the tumor stage, and the Cox proportional hazard (CPH) model had better performance than the machine learning model in terms of effectiveness.

PHE1-based IgG-like antibody platform provides a novel strategy for enhanced T-cell immunotherapy.

Introduction: Bispecific antibodies (BsAbs) can simultaneously target two epitopes of different antigenic targets, bringing possibilities for diversity in antibody drug design and are promising tools for the treatment of cancers and other diseases. T-cell engaging bsAb is an important application of the bispecific antibody, which could promote T cell-mediated tumor cell killing by targeting tumor-associated antigen (TAA) and CD3 at the same time. Methods: This study comprised antibodies purification, Elisa assay for antigen binding, cytotoxicity assays, T cell activation by flow cytometry in vitro and xenogenic tumor model in vivo. Results: We present a novel bsAb platform named PHE-Ig technique to promote cognate heavy chain (HC)-light chain (LC) pairing by replacing the CH1/CL regions of different monoclonal antibodies (mAbs) with the natural A and B chains of PHE1 fragment of Integrin ß2 based on the knob-in-hole (KIH) technology. We had also verified that PHE-Ig technology can be effectively used as a platform to synthesize different desired bsAbs for T-cell immunotherapy. Especially, BCMA×CD3 PHE-Ig bsAbs exhibited robust anti-multiple myeloma (MM) activity in vitro and in vivo. Discussion: Moreover, PHE1 domain was further shortened with D14G and R41S mutations, named PHE-S, and the PHE-S-based BCMA×CD3 bsAbs also showed anti BCMA+ tumor effect in vitro and in vivo, bringing more possibilities for the development and optimization of different bsAbs. To sum up, PHE1-based IgG-like antibody platform for bsAb construction provides a novel strategy for enhanced T-cell immunotherapy.

Worldwide trend in research on Candida albicans and cancer correlations: a comprehensive bibliometric analysis.

Objective: Candida albicans (C. albicans), an opportunistic pathogen, is implicated in the carcinogenesis of various cancers, thereby significantly impacting human health. This study conducts an in-depth analysis of the prevailing research dynamics concerning the relationship between C. albicans and cancer over the past decade, offering a comprehensive overview of the knowledge structure and emerging focal points in this field through bibliometric scrutiny. Methods: A methodical quantitative and visual scrutiny of pertinent literature from the Web of Science Core Collection (WoSCC) spanning the previous decade was carried out employing VOS Viewer and CiteSpace software. Results: From January 1, 2014, to January 1, 2024, a comprehensive corpus of 1,259 articles was delineated. Prominent research institutions included the Egyptian Knowledge Bank, Cairo University, and King Saud University. The top three prolific countries were the United States, China, and India. Among the authors, Mohamed, Gehad G., Mahmoud, Walaa H., and Netea, Mihai G., emerged as the most prolific, with Pfaller, Ma being distinguished as the most frequently cited author. The journal Molecules published the highest number of articles, while PLoS One had the highest citation count. Nature had the highest impact factor. The research focal points in this field encompassed the interactions between C. albicans and cancer, the correlation with oral cancer, the underlying mechanisms of C. albicans carcinogenic potential, as well as antifungal and anticancer therapies. Conclusion: This investigation constitutes a pioneering bibliometric analysis elucidating the trends and advancements in research regarding the correlation between C. albicans and cancer. Said analyses uncover the prevailing research focal points and trends, offering insightful guidance for subsequent inquiry in this domain. Systematic review registration: https://www.webofscience.com/wos/woscc/summary/df33afba-f843-41e8-b932-cb3678eb8243-e92e7316/relevance/1.

Melatonin inhibits circadian gene DEC1 and TLR2/MyD88/NF-κB signaling pathway to alleviate renal injury in type 2 diabetic mice.

BACKGROUND: Diabetic Kidney Disease (DKD) is a complex disease associated with circadian rhythm and biological clock regulation disorders. Melatonin (MT) is considered a hormone with renal protective effects, but its mechanism of action in DKD is unclear. METHODS: We used the GSE151325 dataset from the GEO database for differential gene analysis and further explored related genes and pathways through GO and KEGG analysis and PPI network analysis. Additionally, this study used a type 2 diabetes db/db mouse model and investigated the role of melatonin in DKD and its relationship with clock genes through immunohistochemistry, Western blot, real-time PCR, ELISA, chromatin immunoprecipitation (ChIP), dual-luciferase reporter technology, and liposome transfection technology to study DEC1 siRNA. RESULTS: Bioinformatics analysis revealed the central position of clock genes such as CLOCK, DEC1, Bhlhe41, CRY1, and RORB in DKD. Their interaction with key inflammatory regulators may reveal melatonin's potential mechanism in treating diabetic kidney disease. Further experimental results showed that melatonin significantly improved the renal pathological changes in db/db mice, reduced body weight and blood sugar, regulated clock genes in renal tissue, and downregulated the TLR2/MyD88/NF-κB signaling pathway. We found that the transcription factor DEC1 can bind to the TLR2 promoter and activate its transcription, while CLOCK's effect is unclear. Liposome transfection experiments further confirmed the effect of DEC1 on the TLR2/MyD88/NF-κB signaling pathway. CONCLUSION: Melatonin shows significant renal protective effects by regulating clock genes and downregulating the TLR2/MyD88/NF-κB signaling pathway. The transcription factor DEC1 may become a key regulatory factor for renal inflammation and fibrosis by activating TLR2 promoter transcription. These findings provide new perspectives and directions for the potential application of melatonin in DKD treatment.

Intraplatelet miRNA-126 regulates thrombosis and its reduction contributes to platelet inhibition.

AIMS: MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. METHODS AND RESULTS: Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the PI3 K/AKT pathway, enhancing platelet activation through activating the integrin αIIbß3-mediated outside-in signaling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease of platelet activity. CONCLUSIONS: Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.

Diagnostic yield and complication rates of percutaneous transthoracic CT-guided coaxial needle biopsy in persistent pulmonary consolidation.

OBJECTIVES: To investigate the diagnostic performance and complication rates of percutaneous transthoracic CT-guided coaxial core needle biopsy (PTCNB) in persistent consolidations and evaluate its safety in routine clinical practice. METHODS: A total of 685 patients (404 males, 281 females) underwent PTCNB with coaxial core technique for persisted consolidation were reviewed in this study. According to histopathological and microbiological analysis, the results of biopsy specimens were categorized as follows: malignant, specific benign, non-specific benign and non-diagnostic. The final diagnosis was established through surgical resection or clinicoradiological follow-up for at least 12 months following biopsy. Diagnostic yield of PTCNB was defined as the percentage of the true diagnosis from biopsy as malignant and specific benign lesions. RESULTS: With respect to the final diagnosis, 54 (54/685; 7.88%) cases were obtained by surgery and the remaining were by follow-up. The total accuracy, sensitivity, specificity of PTCNB for malignancy diagnosis was 94.45%, 84.87%, 100%, respectively. Diagnostic yield of PTCNB was 66.28%. Compared to lesions smaller than 3 cm, higher diagnostic yield (70.89%), lower complication incidence (38.22%) and shorter procedure time (8.78 min) were observed in lesions ≥ 3 cm group. CONCLUSION: PTCNB in persistent consolidation is a safe and effective procedure, which provide relatively high diagnostic yield and acceptable complication, especially in size over 3 cm lesions. CRITICAL RELEVANCE STATEMENT: CT-guided coaxial needle biopsy for pulmonary consolidation is a safe and effective procedure. The coaxial needle biopsy yielded high diagnostic rates and low complication rates (including pneumothorax and intrapulmonary hemorrhage), especially in larger lesions.

Simulations on coal water slurry gasification by molecular dynamics method with ReaxFF.

CONTEXT: Coal water slurry (CWS) is a new type of liquid coal product with low pollution, which is mainly used in the chemical industry to produce syngas (CO + H2). It is of great significance to study the microscopic mechanism of CWS gasification reaction for improving the efficiency of coal gasification. In this paper, the method of molecular dynamics based on reaction force fields (ReaxFF-MD) is used to study the gasification process of CWS/O2 system at different temperatures. The results show that, in the range of 1600-2400 K, the macromolecular network structure of lignite is decomposed into a large number of small molecular structures and a small number of light tar free radical fragments, and the types and quantities of reaction products increased rapidly. At 2400-4000 K, the free radical fragments of light tar are further decomposed and reacted with gasification agents, but the types and quantities of reaction products have little change. At 3600 K, a full gasification reaction occurred in the system, and the content of syngas is the highest. METHODS: The model was established and optimized by Materials Studio (MS) software. Based on ReaxFF-MD method, Lammps software was used to simulate the gasification process of CWS/O2 system, and the reaction force field files containing C, H, O, N, and S element were used. By calculating the activation energy of gasification reaction, the rationality of the model and calculation method was illustrated. The post-processing of the results was implemented using OVITO, ChemDraw software, and self-programmed Python scripts.

HOXD10 attenuates renal fibrosis by inhibiting NOX4-induced ferroptosis.

In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-ß1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV-HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-ß1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-ß1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

Exploring the mechanism of Huanglian ointment in alleviating wound healing after anal fistula surgery through metabolomics and proteomics.

Anal fistula is a common anal and intestinal disease. The wound of anal fistula surgery is open and polluting, which is the most difficult to heal among all surgical incisions. To investigate the mechanism of Huanglian ointment (HLO) on wound healing after anal fistula incision. The S. aureus infected wound in SD rats were used to imitate poor healing wound after anal fistula surgery. SD rats with wound sites (n = 24) were randomly divided into four groups (Control group, Model group, Potassium permanganate (PP) treatment group, and HLO treatment group). The wound healing rate was evaluated, HE staining was used to evaluate the pathological changes of each group, ELISA was used to detect the secretion of inflammatory factors in each group, and the mechanism was explored through metabolomics and proteomics in plasma rat. Compared to other groups, the rate of wound healing in the HLO group was higher on days 7 and 14. Histological analysis showed that collagen and fibroblast in HLO rats were significantly increased, inflammatory cells were reduced, and vascular endothelial permeability was increased. ELISA results showed that the secretion of inflammatory factors in HLO rats was significantly lower. Significant proteins and metabolites were identified in the wound tissues of the infected rats and HLO-treated rats, which were mainly attributed to Cdc42, Ctnnb1, Actr2, Actr3, Arpc1b, Itgam, Itgb2, Cttn, Linoleic acid metabolism, d-Glutamine and d-glutamate metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, alpha-Linolenic acid metabolism, and Ascorbate and aldarate metabolism. In conclusion, this study showed that HLO can promote S. aureus infected wound healing, and the data provide a theoretical basis for the treatment of wounds after anal fistula surgery with HLO.

Global trends in Cryptococcus and its interactions with the host immune system: a bibliometric analysis.

Objectives: This manuscript undertakes a systematic examination of the research landscape concerning global Cryptococcus species and their dynamism with the host immune system spanning the past decade. It furnishes a detailed survey of leading knowledge institutions and critical focal points in this area, utilizing bibliometric analysis. Methods: VOSviewer and CiteSpace software platforms were employed to systematically analyze and graphically depict the relevant literature indexed in the WoSCC database over the preceding ten years. Results: In the interval between October 1, 2013, and October 1, 2023, a corpus of 795 publications was amassed. The primary research institutions involved in this study include Duke University, the University of Minnesota, and the University of Sydney. The leading trio of nations, in terms of publication volume, comprises the United States, China, and Brazil. Among the most prolific authors are Casadevall, Arturo; Wormley, Floyd L., Jr.; and Olszewski, Michal A., with the most highly cited author being Perfect, Jr. The most esteemed journal is Mbio, while Infection and Immunity commands the highest citation frequency, and the Journal of Clinical Microbiology boasts the most significant impact factor. Present research foci encompass the intricate interactions between Cryptococcus pathogenesis and host immunity, alongside immune mechanisms, complications, and immunotherapies. Conclusion: This represents the first exhaustive scholarly review and bibliometric scrutiny of the evolving landscapes in Cryptococcus research and its interactions with the host immune system. The analyses delineated herein provide insights into prevailing research foci and trajectories, thus furnishing critical directions for subsequent inquiries in this domain.

The role of PALLD-STAT3 interaction in megakaryocyte differentiation and thrombocytopenia treatment.

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.

Construction of a physiologically based pharmacokinetic model of paclobutrazol and exposure estimation in the human body.

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.

Rapid identification and determination of chemical components of huai yam based on UPLC-Q-Exactive-MS and fragmentation patterns.

Huai Yam (Dioscoreae Rhizoma) contains many active ingredients such as flavonoids, saponins, and amino acids. In this study, an efficient method for the classification and rapid identification of yam components was established based on UPLC-Q-Exactive-MS and data post-processing techniques. First, the mass spectrometry information including the characteristic fragmentations (CFs) and neutral losses (NLs) of yam reported in the literature were summarised and a database of compounds was established. Then, the mass spectrometry data detected by the yam sample are compared with those described in database for rapid identification of target compounds. Finally, 60 compounds were identified, including 18 flavones, 2 saponins, 10 amino acids, 7 organic acids, 3 carbohydrates, 8 fatty acids and 12 others. A new strategy for identifying target constituents based on CFs and NLs was successfully established, laying the foundation for further research on yam and promoting the development of composition analysis of Traditional Chinese Medicine (TCM).