Relationship between changes in late-life blood pressure and the risk of frailty and mortality among older population in China: a cohort study based on CLHLS.

The evidence regarding the effects of blood pressure changes on older individuals remains inconclusive, and the impact of frailty throughout the life course is not known. We investigated the associations of different change patterns of blood pressure during 3-year intervals with frailty and mortality. Participants included 7335 persons from 2008 to 2014 of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Change in blood pressure was calculated as the difference between follow-up and baseline. Frailty was evaluated using a 40-item frailty index. Mortality status was ascertained up to December 31, 2014. The mean age of participants was 82.6 ± 10.7 years. The optimal blood pressure level (SBP, 130-150 mmHg; DBP, 70-90 mmHg) was associated with the lowest risk of frailty while decreasing follow-up SBP and DBP were significantly correlated with frailty. Lower baseline blood pressure levels (SBP < 130 mmHg; DBP < 70 mmHg) were associated with decreased mortality risk when participants increased their blood pressure to optimal levels during follow-up SBP and DBP (0.78, 0.63-0.98), compared to maintaining a steady low SBP (< 130 mmHg) and DBP (< 70 mmHg). For those with DBP around 70-90 mmHg, decreasing follow-up DBP (< 70 mmHg) was associated with higher mortality (1.23, 1.07-1.42) compared to maintaining stable follow-up DBP (70-90 mmHg). These results remain significant after adjusting for frailty. Optimal blood pressure levels were associated with the lowest risk of frailty. The association between lower blood pressure and increased mortality risk persisted even after accounting for frailty. We used a nationally representative longitudinal cohort study by using 2008-2014 of the Chinese Longitudinal Healthy Longevity in China. Change in blood pressure was calculated as the difference between follow-up and baseline. We investigated the associations of different change patterns of blood pressure during 3-year intervals with frailty and mortality.

Cholesterol 25-hydroxylase prevents type 2 diabetes mellitus induced cardiomyopathy by alleviating cardiac lipotoxicity.

OBJECTIVES: Diabetic cardiomyopathy (DCM) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients, with its underlying mechanisms still elusive. This study aims to investigate the role of cholesterol-25-monooxygenase (CH25H) in T2DM induced cardiomyopathy. METHODS: High fat diet combined with streptozotocin (HFD/STZ) were used to establish a T2DM model. CH25H and its product 25-hydroxycholesterol (25HC) were detected in the hearts of T2DM model. Gain- or loss-of-function of CH25H were performed by receiving AAV9-cTNT-CH25H or CH25H knockout (CH25H-/-) mice with HFD/STZ treatment. Cardiac function was evaluated using echocardiography, and cardiac tissues were collected for immunoblot analysis, histological assessment and quantitative polymerase chain reaction (qPCR). Mitochondrial morphology and function were evaluated using transmission electron microscopy (TEM) and Seahorse XF Cell Mito Stress Test Kit. RNA-sequence analysis was performed to determine the molecular changes associated with CH25H deletion. RESULTS: CH25H and 25HC were significantly decreased in the hearts of T2DM mice. CH25H-/- mice treated with HFD/STZ exhibited impaired mitochondrial function and structure, increased lipid accumulation, and aggregated cardiac dysfunction. Conversely, T2DM mice receiving AAV9-CH25H displayed cardioprotective effects. Mechanistically, RNA sequencing and qPCR analysis revealed that CH25H deficiency decreased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target gene expression. Additionally, administration of ZLN005, a potent PGC-1α activator, partially protected against high glucose and palmitic acid induced mitochondria dysfunction and lipid accumulation in vitro. CONCLUSION: Our study provides compelling evidence supporting the protective role of CH25H in T2DM-induced cardiomyopathy. Furthermore, the regulation of PGC-1α may be intricately involved in this cardioprotective process.

Investigating the Immunogenic Cell Death-Dependent Subtypes and Prognostic Signature of Triple-Negative Breast Cancer.

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune "cold" and "hot" phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00133-x.

Investigating potential biomarkers of acute pancreatitis in patients with a BMI>30 using Mendelian randomization and transcriptomic analysis.

BACKGROUND: Acute pancreatitis (AP) has become a significant global health concern, and a high body mass index (BMI) has been identified as a key risk factor exacerbating this condition. Within this context, lipid metabolism assumes a critical role. The complex relationship between elevated BMI and AP, mediated by lipid metabolism, markedly increases the risk of complications and mortality. This study aimed to accurately define the correlation between BMI and AP, incorporating a comprehensive analysis of the interactions between individuals with high BMI and AP. METHODS: Mendelian randomization (MR) analysis was first applied to determine the causal relationship between BMI and the risk of AP. Subsequently, three microarray datasets were obtained from the GEO database. This was followed by an analysis of differentially expressed genes and the application of weighted gene coexpression network analysis (WGCNA) to identify key modular genes associated with AP and elevated BMI. Functional enrichment analysis was then performed to shed light on disease pathogenesis. To identify the most informative genes, machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were employed. Subsequent analysis focused on the colocalization of the Quantitative Trait Loci (eQTL) data associated with the selected genes and Genome-Wide Association Studies (GWAS) data related to the disease. Preliminary verification of gene expression trends was conducted using external GEO datasets. Ultimately, the diagnostic potential of these genes was further confirmed through the development of an AP model in mice with a high BMI. RESULTS: A total of 21 intersecting genes related to BMI>30, AP, and lipid metabolism were identified from the datasets. These genes were primarily enriched in pathways related to cytosolic DNA sensing, cytokine‒cytokine receptor interactions, and various immune and inflammatory responses. Next, three machine learning techniques were utilized to identify HADH as the most prevalent diagnostic gene. Colocalization analysis revealed that HADH significantly influenced the risk factors associated with BMI and AP. Furthermore, the trend in HADH expression within the external validation dataset aligned with the trend in the experimental data, thus providing a preliminary validation of the experimental findings.The changes in its expression were further validated using external datasets and quantitative real-time polymerase chain reaction (qPCR). CONCLUSION: This study systematically identified HADH as a potential lipid metabolism-grounded biomarker for AP in patients with a BMI>30.

Dietary polyphenols regulate appetite mechanism via gut-brain axis and gut homeostasis.

Nowadays, due to the rise of fast-food consumption, the metabolic diseases are increasing as a result of high-sugar and high-fat diets. Therefore, there is an urgent need for natural, healthy and side-effect-free diets in daily life. Whole grain supplementation can enhance satiety and regulate energy metabolism, effects that have been attributed to polyphenol content. Dietary polyphenols interact with gut microbiota to produce intermediate metabolites that can regulate appetite while also enhancing prebiotic effects. This review considers how interactions between gut metabolites and dietary polyphenols might regulate appetite by acting on the gut-brain axis. In addition, further advances in the study of dietary polyphenols and gut microbial metabolites on energy metabolism and gut homeostasis are summarized. This review contributes to a better understanding of how dietary polyphenols regulate appetite via the gut-brain axis, thereby providing nutritional references for citizens' dietary preferences.

Association of IL-17 Inhibitors with Hypertension in Patients with Autoimmune Diseases: A Systematic Review and Meta-analysis on Randomized Controlled Trials.

The influence of IL-17 inhibition on blood pressure in autoimmune disease patients remains inconclusive. Our objective is to examine the risk of hypertension in patients with autoimmune diseases undergoing IL-17 inhibition therapies via meta-analysis of randomized, placebo-controlled trials (RCTs). We obtained integrated data from PubMed, Embase, and ClinicalTrials.gov. Incident hypertension rates were calculated, and hazard ratios (HRs) with 95% confidence intervals (CIs) were analyzed, along with Ι^2 statistics to assess heterogeneity. Sequential analysis ensured conclusion reliability. In 30 RCTs involving 9,909 patients with diverse autoimmune diseases treated with anti-IL-17 agents, our meta-analysis revealed a significant increase in hypertension risk (RR 1.69, CI 1.24-2.31, p=0.001), robustly supported by trial sequential analysis. Among the four agents (secukinumab, ixekizumab, bimekizumab, and brodalumab), only secukinumab exhibited a notable association with hypertension. Patients with various primary autoimmune diseases, particularly those with psoriatic arthritis, had a higher likelihood of developing hypertension; in rheumatic arthritis patient cohorts, anti-IL-17 agents did not elevate hypertension risk. Prolonged treatment duration correlated with an increased hypertension risk. Stratifying by gender, studies with a female predominance demonstrated a higher risk ratio for hypertension compared to male-predominant studies. This highlights that anti-IL-17 treatment escalates hypertension risk, emphasizing the need for extra caution when managing autoimmune disease patients. (Registered by PROSPERO, CRD42016053112).

Association of macronutrient consumption quality, food source and timing with depression among US adults: A cross-sectional study.

BACKGROUND: Growing evidence suggests that meal timing may influence dietary choices and mental health. Thus, this study examined the association between macronutrient consumption quality, food source, meal timing, and depression prevalence in Americans. METHODS: 23,313 National Health and Nutrition Survey participants from 2007 to 2016 were included in this cross-sectional study. Macronutrient intake was calculated for all day, dinner, and breakfast and subtypes into 4 classes. Based on the Patient Health Questionnaire, depression was defined as a 9-item score ≥ 10 on the PHQ-9. The correlation between macronutrients and depression prevalence was estimated with multivariable logistic regression models and isocaloric substitution effects. RESULTS: Low-quality carbohydrates (OR = 1.54, 95 % CI: 1.11, 2.12) were positively linked to depression compared with the lowest quartile, after adjusting for age and other covariates. In contrast, total high-quality carbohydrate (OR = 0.52, 95 % CI: 0.40, 0.66), total animal protein (OR = 0.60, 95 % CI: 0.45, 0.80), and total vegetable protein (OR = 0.61, 95 % CI: 0.43, 0.85) were negatively associated with depression was negatively associated. Replacing low-quality carbohydrates with high-quality carbohydrates throughout the day reduced the risk of depression by approximately 15 %. LIMITATIONS: Cross-sectional data. CONCLUSION: All in all, diet plays a crucial role in the prevention and treatment of depression. Especially in terms of macronutrient intake, high-quality, moderate intake can reduce the risk of depression. However, different subtypes of macronutrient consumption may have different effects on depression, so it becomes crucial to carefully consider the selection and combination of macronutrients.

Still water run deep: Therapeutic TP effect of ucMSC-Ex via regulating mTOR to enhance autophagy.

Our previous study confirmed that umbilical cord mesenchymal stem cells-exosomes (ucMSC-Ex) inhibit apoptosis of pancreatic acinar cells to exert protective effects. However, the relationship between apoptosis and autophagy in traumatic pancreatitis (TP) has rarely been reported. We dissected the transcriptomics after pancreatic trauma and ucMSC-Ex therapy by high-throughput sequencing. Additionally, we used rapamycin and MHY1485 to regulate mTOR. HE, inflammatory factors and pancreatic enzymatic assays were used to comprehensively determine the local versus systemic injury level, fluorescence staining and electron microscopy were used to detect the effect of autophagy, and observe the expression levels of autophagy-related markers at the gene and protein levels. High-throughput sequencing identified that autophagy played a crucial role in the pathophysiological process of TP and ucMSC-Ex therapy. The results of electron microscopy, immunofluorescence staining, polymerase chain reaction and western blot suggested that therapeutic effect of ucMSC-Ex was mediated by activation of autophagy in pancreatic acinar cells through inhibition of mTOR. ucMSC-Ex can attenuate pancreas injury by inhibiting mTOR to regulate acinar cell autophagy after TP. Future studies will build on the comprehensive sequencing of RNA carried by ucMSC-Ex to predict and verify specific non-coding RNA.

Identification of a transcription factor AoMsn2 of the Hog1 signaling pathway contributes to fungal growth, development and pathogenicity in Arthrobotrys oligospora.

INTRODUCTION: Arthrobotrys oligospora has been utilized as a model strain to study the interaction between fungi and nematodes owing to its ability to capture nematodes by developing specialized traps. A previous study showed that high-osmolarity glycerol (Hog1) signaling regulates the osmoregulation and nematocidal activity of A. oligospora. However, the function of downstream transcription factors of the Hog1 signaling in the nematode-trapping (NT) fungi remains unclear. OBJECTIVE: This study aimed to investigate the functions and potential regulatory network of AoMsn2, a downstream transcription factor of the Hog1 signaling pathway in A. oligospora. METHODS: The function of AoMsn2 was characterized using targeted gene deletion, phenotypic experiments, real-time quantitative PCR, RNA sequencing, untargeted metabolomics, and yeast two-hybrid analysis. RESULTS: Loss of Aomsn2 significantly enlarged and swollen the hyphae, with an increase in septa and a significant decrease in nuclei. In particular, spore yield, spore germination rate, traps, and nematode predation efficiency were remarkably decreased in the mutants. Phenotypic and transcriptomic analyses revealed that AoMsn2 is essential for fatty acid metabolism and autophagic pathways. Additionally, untargeted metabolomic analysis identified an important function of AoMsn2 in the modulation of secondary metabolites. Furtherly, we analyzed the protein interaction network of AoMsn2 based on the Kyoto Encyclopedia of Genes and Genomes pathway map and the online website STRING. Finally, Hog1 and six putative targeted proteins of AoMsn2 were identified by Y2H analysis. CONCLUSION: Our study reveals that AoMsn2 plays crucial roles in the growth, conidiation, trap development, fatty acid metabolism, and secondary metabolism, as well as establishes a broad basis for understanding the regulatory mechanisms of trap morphogenesis and environmental adaptation in NT fungi.

B cell subsets contribute to myocardial protection by inducing neutrophil apoptosis after ischemia and reperfusion.

A robust, sterile inflammation underlies myocardial ischemia and reperfusion injury (MIRI). Several subsets of B cells possess the immunoregulatory capacity that limits tissue damage, yet the role of B cells in MIRI remains elusive. Here, we sought to elucidate the contribution of B cells to MIRI by transient ligation of the left anterior descending coronary artery in B cell-depleted or -deficient mice. Following ischemia and reperfusion (I/R), regulatory B cells are rapidly recruited to the heart. B cell-depleted or -deficient mice exhibited exacerbated tissue damage, adverse cardiac remodeling, and an augmented inflammatory response after I/R. Rescue and chimeric experiments indicated that the cardioprotective effect of B cells was not solely dependent on IL-10. Coculture experiments demonstrated that B cells induced neutrophil apoptosis through contact-dependent interactions, subsequently promoting reparative macrophage polarization by facilitating the phagocytosis of neutrophils by macrophages. The in vivo cardioprotective effect of B cells was undetectable in the absence of neutrophils after I/R. Mechanistically, ligand-receptor imputation identified FCER2A as a potential mediator of interactions between B cells and neutrophils. Blocking FCER2A on B cells resulted in a reduction in the percentage of apoptotic neutrophils, contributing to the deterioration of cardiac remodeling. Our findings unveil a potential cardioprotective role of B cells in MIRI through mechanisms involving FCER2A, neutrophils, and macrophages.

Associations of the magnesium depletion score and magnesium intake with diabetes among US adults: an analysis of the National Health and Nutrition Examination Survey 2011-2018.

Objectives: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. Methods: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the nonlinear association between magnesium intake and diabetes using restricted cubic spline analysis. Results: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-SD increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR=0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR=1.35; 95% CI, 1.18 to 1.55), middle (PR=1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR=1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR=0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR=0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). Conclusion: MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Dissecting Maillard reaction production in fried foods: Formation mechanisms, sensory characteristic attribution, control strategy, and gut homeostasis regulation.

Foods rich in carbohydrates or fats undergo the Maillard reaction during frying, which promotes the color, flavor and sensory characteristics formation. In the meanwhile, Maillard reaction intermediates and advanced glycation end products (AGEs) have a negative impact on food sensory quality and gut homeostasis. This negative effect can be influenced by food composition and other processing factors. Whole grain products are rich in polyphenols, which can capture carbonyl compounds in Maillard reaction, and reduce the production of AGEs during frying. This review summarizes the Maillard reaction production intermediates and AGEs formation mechanism in fried food and analyzes the factors affecting the sensory formation of food. In the meanwhile, the effects of Maillard reaction intermediates and AGEs on gut homeostasis were summarized. Overall, the innovative processing methods about the Maillard reaction are summarized to optimize the sensory properties of fried foods while minimizing the formation of AGEs.

Recognition of methamphetamine and other amines by trace amine receptor TAAR1.

Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the endogenous ß-phenylethylamine (ß-PEA)1 as well as methamphetamine2, an abused substance that has posed a severe threat to human health and society3. Given its unique physiological role in the brain, TAAR1 is also an emerging target for a range of neurological disorders including schizophrenia, depression and drug addiction2,4,5. Here we report structures of human TAAR1-G-protein complexes bound to methamphetamine and ß-PEA as well as complexes bound to RO5256390, a TAAR1-selective agonist, and SEP-363856, a clinical-stage dual agonist for TAAR1 and serotonin receptor 5-HT1AR (refs. 6,7). Together with systematic mutagenesis and functional studies, the structures reveal the molecular basis of methamphetamine recognition and underlying mechanisms of ligand selectivity and polypharmacology between TAAR1 and other monoamine receptors. We identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in the ligand-binding pockets, which may contribute to the ligand recognition in TAAR1. These findings shed light on the ligand recognition mode and activation mechanism for TAAR1 and should guide the development of next-generation therapeutics for drug addiction and various neurological disorders.

CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway.

Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway-associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway-related intermediate metabolites and elevates NADP+ /NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR-212-5p to upregulate c-Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR-212-5p/c-Met axis plays a key role in oxidative pentose phosphate pathway-mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer.

Association between low-density lipoprotein cholesterol level and all-cause mortality in idiopathic dilated cardiomyopathy patients: a single-institutional study.

AIMS: To determine the association between all-cause mortality and low-density lipoprotein cholesterol (LDL-C) in patients with idiopathic cardiomyopathy (iDCM). BACKGROUND: LDL-C had long been considered as a dangerous predictor of cardiovascular diseases; however, the correlation between them was not fully clarified. METHODS: A total of 1058 patients who met the World Health Organization criteria for iDCM in West China Hospital (2009-2016) were enrolled in this retrospective study. Baseline demographic characteristics and correlations between variables were calculated and analyzed, and potential predictors were explored using univariate and multivariate regressions. Cox proportional hazards models were used to determine correlation on a continuous scale. RESULTS: LDL-C is an independent prognostic factor and higher LDL-C levels are associated with better prognosis in iDCM patients according to cox regression analysis. Compared with individuals which LDL > 2.28 mmol/L (75th-100th percentile), the multivariable-adjusted hazard ratio for all-cause mortality was 1.52 (95%CI: 1.03-2.26) in patients with LDL-C < 1.78 mmol/L (0-25th percentile). In patients with New York Heart Association function III and IV, LDL-C levels have a hazard ratio of 0.83 (confidence interval 0.73-0.95). CONCLUSIONS: In patients with iDCM, lower LDL-C level was associated with an increased risk of all-cause mortality. The correlation between mortality and LDL-C level was stronger in patients with worse heart function. LDL-C levels have a potential predictive value in iDCM patients.

A Strong Adhesive Biological Hydrogel for Colon Leakage Repair and Abdominal Adhesion Prevention.

Colon leakage is one of the most severe complications in abdominal trauma or surgery cases. It can lead to severe abdominal infection and abdominal adhesions, resulting in prolonged hospital stays and increased mortality. In this study, a photosensitive hydrogel is proposed, which can swiftly form a strong adhesion coating on the damaged colon after UV irradiation, to realize quick cure and suture-free repair of colon leakage. The newly developed biological gel consists of hyaluronic acid methacryloyl (HAMA) and hyaluronic acid o-nitroso benzaldehyde (HANB) in the optimal ratio of 3: 1, which exerts both the rapid photocuring properties of HAMA and the strong tissue adhesion properties of HANB. HAMA/HANB shows excellent adhesion stability on wet surfaces, presenting controllable mechanical properties, ductility, adhesion stability, and chemical stability; it also evades foreign body response, which relieves the degree of abdominal adhesion. The underlying mechanism for HAMA/HANB promoting wound healing in colon leakage involves the reconstruction of the colon barrier, as well as the regulation of the immune reaction and neovascularization. In all, HAMA/HANB is a promising alternative suture-free approach for repairing colon leakage; it has a reliable healing effect and is expected to be extended to clinical application for other organ injuries.

Global Trends in Research of Antimicrobial Peptides for the Treatment of Drug-Resistant Bacteria from 1995 to 2021: A Bibliometric Analysis.

Background: Antimicrobial peptides (AMPs) can act on the bacterial cell membrane to play an antibacterial role in types of drug-resistant bacteria. Therefore, AMPs have attracted more and more attention in the treatment of drug-resistant bacteria. Methods: Bibliometric analysis was employed to sort out the development and trends in the research of AMPs in the treatment of drug-resistant bacteria and map the knowledge structure for scholars. Results: Since 2010, the publications and citations in this field have exploded, indicating a growing global interest in the field of AMPs for the treatment of drug-resistant bacteria. And as major countries in this field, China and the USA had conducted very in-depth exchanges and cooperation, which had injected a steady stream of impetus into this field. Both old and new scholars have made efforts, and related fields have developed rapidly, especially in the synthesis and improvement of novel AMPs. In recent years, research directions in the field of AMPs for the treatment of drug-resistant bacteria gradually focused on the practical application, optimization of drug delivery mode, optimization of synthesis mode, screening of new AMPs and other fields, indicating that the relevant research results of AMPs for the treatment of drug-resistant bacteria had entered the actual clinical stage, with higher practical significance. Conclusion: The research history, global research status, future research hotspots, and trends of the research of AMPs in the treatment of drug-resistant bacteria were discussed in depth in this study, which can provide research references and inspiration for researchers inside and outside the related field.

Macrocyclization of linear molecules by deep learning to facilitate macrocyclic drug candidates discovery.

Interest in macrocycles as potential therapeutic agents has increased rapidly. Macrocyclization of bioactive acyclic molecules provides a potential avenue to yield novel chemical scaffolds, which can contribute to the improvement of the biological activity and physicochemical properties of these molecules. In this study, we propose a computational macrocyclization method based on Transformer architecture (which we name Macformer). Leveraging deep learning, Macformer explores the vast chemical space of macrocyclic analogues of a given acyclic molecule by adding diverse linkers compatible with the acyclic molecule. Macformer can efficiently learn the implicit relationships between acyclic and macrocyclic structures represented as SMILES strings and generate plenty of macrocycles with chemical diversity and structural novelty. In data augmentation scenarios using both internal ChEMBL and external ZINC test datasets, Macformer display excellent performance and generalisability. We showcase the utility of Macformer when combined with molecular docking simulations and wet lab based experimental validation, by applying it to the prospective design of macrocyclic JAK2 inhibitors.

The future of robotic pancreaticoduodenal surgery: a bibliometric analysis.

OBJECTIVES: Robotic pancreaticoduodenectomy (RPD) has garnered significant research attention in the last decade. However, no bibliometric studies have been conducted on this field yet. Therefore, the aim of this study is to provide an up-to-date analysis of the current state of research, as well as future trends and hotspots in RPD, through a bibliometric analysis. MATERIALS AND METHODS: We conducted a thorough search of all literature related to RPD in the Web of Science Core Collection (WoSCC). We then analyzed this literature for a variety of factors, including authorship, country of origin, institutional affiliations, and keywords. To visualize our findings, we utilized Citespace 6.1.R3, which enabled us to create network visualization maps, perform cluster analysis, and extract burst words. RESULTS: A total of 264 articles were retrieved. Zureikat is the author with the largest contribution in this field, and Surgical Endoscopy and Other International Techniques is the journal with the largest number of papers in this field. The United States is the core research country in this field. The University of Pittsburgh is the most productive institution. According to the data, outcome, pancreas fistula, definition, risk factor, stay, survival, learning curve and experience are recognized as research hotspots in this field. CONCLUSIONS: This study is the first bibliometric study in the field of RPD. Our data will help us better understand the development trend of the field, and determine research hotspots and research directions. The research results provide practical information for other scholars to understand key directions and cutting-edge information.

Pathophysiological Association of Alzheimer's Disease and Hypertension: A Clinical Concern for Elderly Population.

Alzheimer's disease (AD), the most common cause of dementia and the fifth leading cause of death in the adult population has a complex pathophysiological link with hypertension (HTN). A growing volume of published literature on a parallel elevation of blood pressure (BP), amyloid plaques, and neurofibrillary tangles formation in post-middle of human brain cells has developed new, widely accepting foundations on this association. In particular, HTN in elderly life mediates cerebral blood flow dysfunction, neuronal dysfunction, and significant decline in cognitive impairment, primarily in the late-life populace, governing the onset of AD. Thus, HTN is an established risk factor for AD. Considering the impact of AD, 1.89 million deaths annually, and the failure of palliative therapies to cure AD, the scientific research community is looking to adopt integrated approaches to target early modified risk factors like HTN to reduce AD burden. The current review highlights the significance and impact of HTN-based prevention in lowering the AD burden in the elderly by providing a comprehensive overview of the physiological relationship between AD and HTN with an in-detail explanation of the role and applications of pathological biomarkers in this clinical association. The review will gain worth in presenting new insights and providing inclusive discussion on the correlation between HTN and cognitive impairment. It will increase across a wider scientific audience to expand understanding of this pathophysiological association.