Search

The study reported herein investigated age difference in trunk kinematics during walking with different backpack weights. Two groups of boys, aged 6 and 12 years old, participated in the study. A multiple trial test was conducted with backpacks loaded with 0%, 10%, 15%, and 20% of each subject's body weight. The subjects walked on a treadmill at a self-selected comfortable speed for 20 min. The movements of the subjects in sagital plan were filmed and analyzed. The results indicate that trunk inclination angle progressively increased with the increase backpack weight in both age groups. Carrying a load heavier than 15% of body weight resulted in a significantly increased trunk inclination angle when compared to no load. The 12-year-old children showed a significantly lager amplitude in the trunk inclination angle than the 6-year-old children when carrying the same backpack weight. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the gait pattern and metabolic responses of walking with negative heel shoes as compared to walking with normal shoes. Nineteen female subjects were recruited, of whom 13 (aged 23.08 +/- 3.9 years, body weight 50.18 +/- 5.3 kg, and body height 1.63 +/- 0.05 m) participated in the gait pattern study, and 6 (age 32.8 t 6.6 years, body weight 58.3 +/- 5.8 kg, and body height 1.64 +/- 0.01 m) in the metabolic study. In the gait pattern study, movement kinematics and kinetic data were obtained by video analysis and force platform measurement during the process of walking at a constant speed of 1.33 m/s on a treadmill and over ground, respectively. In the metabolic study, heart rate and oxygen consumption were monitored during treadmill walking. The results showed that there was a significant difference between walking on a treadmill with negative heel shoes and walking with normal shoes, in terms of stride cycle time, cadence, stride length, and angles of the ankle, knee, and hip joints. Differences also were found with the maximum and minimum ground reaction forces and their occurrence times. Metabolically, heart rate and oxygen consumption showed a significant difference. In conclusion, walking with negative heel shoes induced significant changes in gait patterns, ground reaction forces, and energy consumption. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of carrying method and load weight on movement kinematics of children during stair walking. The carrying methods examined included the backpack and the one-strap athletic bag. The load weights included 0%, 10%, 15%, and 20% of body weight. Thirteen students (aged 12.21 +/- 0.98 years) participated in this study. A twodimensional video filming recorded the complete gait cycles of the subjects with each combination of carrying method and load weight when they ascended and descended stairs. Results showed that loads of 10% of body weight or greater induced significantly greater trunk forward inclination in subjects ascending stairs, whereas athletic bags were found to cause a greater trunk range of motion than the backpack during stair descent. Attention should be paid to the loads of school bags carried by children when stair walking is required in school activities. The backpack was found to be safer than the one-strap athletic bag for children stair walking. [ABSTRACT FROM AUTHOR]

Objectives: To assess the characteristic effects of Tai Chi Chuan (TCC) exercise on metabolism and cardiorespiratory response, and to measure its effect on cardiorespiratory function, mental control, immune capacity, and the prevention of falls in elderly people.Design: A review of controlled experimental studies and clinical trials designed with one of two aims: either to assess physiological responses during the performance of TCC or to assess the impact of this exercise on general health and fitness.Main Outcome Measures: Metabolic rate, heart rate, blood pressure, ventilation, maximal oxygen uptake (VO(2)MAX), immune capacity, falls, and fall related factors.Subjects: A total of 2216 men and women.Results: Under review were 31 original studies, published in Chinese or English journals, that met the criteria for inclusion. Most of the papers written in Chinese had not been introduced into the Western literature. Nine of these studies showed that TCC can be classified as moderate exercise, as its does not demand more than 55% of maximal oxygen intake. When this form of exercise and others conducted at equal intensity were compared, TCC showed a significantly lower ventilatory equivalent (VE/VO(2)MAX). Evidence provided by cross sectional and longitudinal studies suggests that TCC exercise has beneficial effects on cardiorespiratory and musculoskeletal function, posture control capacity, and the reduction of falls experienced by the elderly.Conclusions: TCC is a moderate intensity exercise that is beneficial to cardiorespiratory function, immune capacity, mental control, flexibility, and balance control; it improves muscle strength and reduces the risk of falls in the elderly. [ABSTRACT FROM AUTHOR]

Background: Tai Chi Chuan (TTC) exercise has beneficial effects on the components of physical condition and can produce a substantial reduction in the risk of multiple falls. Previous studies have shown that short term TCC exercise did not improve the scores in the single leg stance test with eyes closed and the sit and reach test. There has apparently been no research into the effects of TCC on total body rotation flexibility and heart rate responses at rest and after a three minute step test.Methods: In this cross sectional study, 28 male TCC practitioners with an average age of 67.5 years old and 13.2 years of TCC exercise experience were recruited to form the TCC group. Another 30 sedentary men aged 66.2 were selected to serve as the control group. Measurements included resting heart rate, left and right single leg stance with eyes closed, modified sit and reach test, total body rotation test (left and right), and a three minute step test.Results: Compared with the sedentary group, the TCC group had significantly better scores in resting heart rate, three minute step test heart rate, modified sit and reach, total body rotation test on both right and left side (p < 0.01), and both right and left leg standing with eyes closed (p < 0.05). According to the American Fitness Standards, the TCC group attained the 90th percentile rank for sit and reach and total body rotation test, right and left.Conclusion: Long term regular TCC exercise has favourable effects on the promotion of balance control, flexibility, and cardiovascular fitness in older adults. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effect of "Xingshen-Jieyu" (inducing resuscitation and dispel ling melancholy) electroacupuncture (EA) on serum metabolites in patients with depression and its underlying mechanisms through serum non-targeted metabolomics., Methods: Fifteen depression patients were subjected into the EA group, and 15 healthy volunteers were matched into the healthy group. EA (2 Hz/15 Hz, a tolerable strength) was applied to Baihui (GV20), Shenting (GV24), Toulinqi (GB15), Benshen (GB13), Touwei (ST8), Xuanli (GB6) and Qubin (GB7) for 30 min, 3 times a week for 6 weeks. The severity of depression was assessed using Hamilton Depression Scale-17 (HAMD-17) and Hamilton Anxiety Scale (HAMA), the degree of fatigue was evaluated using Fatigue Scale-14 (FS-14). The subjects sleep quality was assessed using Pittsburgh sleep quality index (PSQI). Blood samples were collected before and after the treatment for processing serum to perform non-targeted metabolomics profile detection using ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), and Partial Least Squares Discriminant Analysis (PLS-DA, a statistical approach). Differential metabolites were screened and pathway enrichment analysis was performed., Results: After the treatment, the scores of HAMD-17, HAMA, PSQI and FS-14 of depression patients were significantly lowered in the EA group ( P <0.05). Compared with the healthy subjects, 46 differential metabolites (21 up-regulated, 25 down-regulated) were screened in patients with depression. Compared with pre-treatment in the EA group, 19 differential (17 up-regulated, and 2 down-regulated) metabolites were screened. Four down-regulated metabolites of the 46 differential metabolites in depression patients were recovered after EA treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differential metabolites before and after EA showed that 19 metabolic pathways were enriched, mainly involving glutaminergic synapses, GABAergic synapses and several amino acid metabolism related pathways., Conclusions: "Xingshen-Jieyu" EA mainly regulates the metabolism of amino acids, and activities of neurotransmitter glutamate and GABA, and restores the excitatory/inhibitory balance, thus playing a role in improving depression.

Background: Nanozymes have the advantages of cost effective, simple synthesis, high durability and stability, and have been widely used in various fields. However, only a few nanomaterials with multiple enzyme-like activity have been reported, and most of the currently developed nanozymes are usually used in colorimetric or fluorescence analysis depending on a single colorimetric or fluorescence signal output. In this study, a copper-based dual-ligand biomimetic nanoflower (Cu-MN) was constructed, which demonstrated potential multiple enzyme-like activity, and was applied to the multi-mode detection of 2,4-dichlorophenol (2,4-DP), epinephrine (EP), and H 2 O 2 ., Results: The laccase-like activity of Cu-MN can catalyze the conversion of 2,4-DP and EP, resulting in the formation of red and yellow-brown oxidation products with distinct UV absorption peaks at 510 nm and 485 nm, respectively. Furthermore, the fluorescence emission peak at 426 nm of Cu-MN can be dynamic quenched during substrate oxidation due to the fluorescence internal filtration effect (IFE). Therefore, a dual-mode analysis method was constructed to detect 2,4-DP and EP by fluorescence and ultraviolet colorimetry, which was successfully applied in natural lake water and rabbit plasma analysis, respectively. Furthermore, a colorimetric sensing strategy based on the peroxidase-like activity of Cu-MN was developed and successfully applied to the monitoring of H 2 O 2 in hydrogen peroxide disinfectant. Additionally, the visualization analysis method was also established by RGB reading of the smartphone., Significance and Novelty: In brief, inspired by the fluorescence characteristics of 2-aminoterephthallc acid and the imidazole group of 2-methylimidazole, a novel copper-based dual-ligand biomimetic nanoflower (Cu-MN) was prepared and used to establish multi-mode method for the detection of 2,4-DP, EP, and H 2 O 2 , which opens up new avenues for its applications in bioanalysis and environmental monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Safflower, the florets of Carthamus tinctorius L., is a widely used traditional Chinese medicine for promoting circulation and improving dysmenorrhea. Polysaccharides is one of the principal water-soluble components in Safflower, which recently endowed with a variety of biological activities, thus making them have important research significance in the field of ethnopharmacology., Aim of the Study: This review summarized the latest research progress on the preparation technology, structural characteristics, and pharmacological effects of Safflower polysaccharides. Moreover, by comparing the structural characteristic of Safflower polysaccharides, the potential structure-activity relationship of Safflower polysaccharides was also discussed., Materials and Methods: This article used keywords including Safflower polysaccharide, Carthamus tinctorius L polysaccharide, Safflower polysaccharide extraction and separation, Safflower polysaccharide structure, and Safflower polysaccharide anti-tumor effects to search for all relevant literature in PubMed, Web of Science, Google Scholar, ScienceDirect, CNKI and other databases from the establishment of the database to July 2024., Results: Summarizing current research findings, seventeen homogeneous Safflower polysaccharides have been obtained. Their structural characteristics, including molecular weights, monosaccharide composition, sugar residue types, glycosidic bond configuration, and the linkage sequence, were initially researched. In terms of pharmacological activity, Safflower polysaccharides exhibit a wide range of biological activities, including immune regulation, anti-tumor effects, and antioxidant properties. Furthermore, the structural characteristics of Safflower polysaccharides significantly influence its biological activities, encompassing factors such as molecular weight, monosaccharide composition, and degree of branching., Conclusion: Safflower polysaccharides have seen significant advancements in recent years regarding preparation methods, structural characterization, and pharmacological studies. These achievements would provide a theoretical basis for the application of Safflower polysaccharide in the field of ethnopharmacology. While Safflower polysaccharides exhibit diverse biological activities and significant potential for development and utilization, further in-depth research is needed to enhance our understanding of their mechanisms of action and optimize their clinical applications., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Recent studies suggest that among the gamma-aminobutyric acid type A (GABA A )receptor subtype heterogeneity, α 2/ α 3 subunits of GABA A receptors mediate pain processing. Therefore, α 2/ α 3 subtype-selective GABA A receptor-positive allosteric modulators (PAMs) may be candidate analgesics. Antinociceptive effects of α 2/ α 3 subtype-selective GABA A receptor PAMs have been reported, but the behavioral effects of these compounds have not been systematically evaluated. This study examined the behavioral effects of two α 2/ α 3 subtype-selective GABA A receptor PAMs, KRM-II-81 and NS16085, in male rats. The antinociceptive effects of KRM-II-81 and NS16085 were examined using rat models of inflammatory (complete Freund's adjuvant) and neuropathic pain (chronic constriction injury). The effect of KRM-II-81 on affective pain was measured using the place escape/avoidance paradigm (PEAP). Rate-response of food-maintained operant responding, horizontal wire test, and the spontaneous alternation T-maze were assessed to study the side-effect profiles of KRM-II-81 and NS16085. The benzodiazepine midazolam was used as a comparator in these studies. KRM-II-81 and NS16085 attenuated mechanical allodynia but not thermal hyperalgesia in both pain states, and their effects were attenuated by the benzodiazepine receptor antagonist flumazenil. KRM-II-81 attenuated affective pain-related behavior in the PEAP test. In the operant responding procedure and horizontal wire test, only midazolam produced significant effects at the dose that produced maximal antinociception. In the T-maze assay, only midazolam significantly decreased the percentage of alternation at an antinociceptive dose. Thus, KRM-II-81 and NS16085 but not midazolam selectively produced antinociceptive effects. Collectively, these data suggest that α 2/ α 3 subtype-selective GABA A PAMs could be a novel class of analgesics and warrant further investigation. SIGNIFICANCE STATEMENT: This study demonstrates that α2/α3 subtype-selective GABA A PAMs KRM-II-81 and NS16085 produce selective antinociceptive effects devoid of sedation, myorelaxation, and cognitive impairment in two rat models of persistent pain. This study supports the development of α2/α3 subtype-selective GABA A PAMs, rather than classical benzodiazepines, as safe and novel analgesics for pain management., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Introduction: Air pollution and transportation noise pollution has been linked to gastrointestinal (GI) diseases, but their relationship remains unclear., Methods: We extracted the significantly modulated genes and CpG sites related to air pollution (PM2.5, PM10, and NOx) and transportation noise pollution (aircraft, railway, and traffic road noise) from previous published studies. Genome-wide methylation analysis and colocalization analysis with these CpG sites and GWAS data of GI diseases were performed to disentangle the relationship between pollution-related blood DNA methylation (DNAm) alterations and GI diseases risk. Summary-based Mendelian randomization (SMR) analysis assessed the impact of pollution-related genes on GI diseases risk across methylation, gene expression, and protein levels. Enrichment analysis investigated the implicated biological pathways and immune cell types., Results: DNAm at cg00227781 [CD300A] (modulated by NOx exposure) and cg19215199 [ZMIZ1] (modulated by PM2.5 exposure) was significantly linked to increased noninfective enteritis and colitis risk, while cg08500171 [BAT2] (modulated by NOx exposure) is significantly associated with an increased gastroesophageal reflux disease (GERD) risk. Colocalization analysis provides strong evidence supporting a shared causal variant between these associations. Multi-omics levels SMR analysis revealed that pollution-modulated lower DNAm at 5 specific CpG sites were associated with increased expression of 4 genes (IL21R, EVPL, SYNGR1, and WDR46), subsequently increasing the risk of GERD, ulcerative colitis, and gastric ulcer. 7 circulating proteins coded by pollution-modulated genes were observed to be associated with 6 GI diseases risk. Enrichment analysis implicates immune and inflammatory responses, MAPK signaling, and telomere maintenance in these pollution-induced effects., Conclusion: We identified potential links between air and transportation noise pollution-related gene methylation, expression, and protein abundance with GI diseases risk, possibly revealing new therapeutic targets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ying-Xuan Chen reports article publishing charges was provided by National Natural Science Foundation of China. Ying-Xuan Chen reports article publishing charges was provided by Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The association between the frailty index (FI) and the risk of chronic lung diseases (CLDs) remains unexplored, warranting further research., Methods and Materials: This study investigated the relationship between FI and CLD risk using data from the China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), comprising a combined sample of 9642 individuals. Propensity score weighting was used to ensure similar distribution of covariates across FI groups. The Wilcoxon rank-sum test was used to analyze differences in FI scores between groups with and without CLD. Kaplan-Meier curves and Cox regression analysis were employed to explore the association between frailty status and CLD incidence, with sensitivity analyses conducted for validation., Results: Higher FI scores were significantly associated with increased CLD risk in both cohorts (p < .05). Kaplan-Meier survival and Cox regression analyses indicated that frail individuals have a significantly elevated risk of CLD compared to robust individuals, particularly in certain subgroups (e.g., female) within the CHARLS cohort (p < .05). The ELSA cohort yielded similar results (p < .05), affirming FI as a strong predictor of CLD. Additional risk factors identified included age, smoking, and unmarried status (p < .05). Frail individuals consistently exhibited the highest risk in both cohorts (CHARLS HR = 1.54, p = .003; ELSA HR = 6.64, p < .001). The sensitivity analysis did not substantially alter the significant associations., Conclusion: These findings emphasize the critical role of frailty in the development of CLD, suggesting that targeted interventions could reduce CLD risk., (© 2024. The Author(s).)

Objective: Lymph node metastasis (LNM) is one of the most common pathways of metastasis in non-small cell lung cancer (NSCLC). Preoperative assessment of occult lymph node metastasis (OLNM) in NSCLC patients is beneficial for selecting appropriate treatment plans and improving patient prognosis., Method: A total of 370 NSCLC patients were included in the study. Univariate and multivariate logistic regression analysis were used to screen potential risk factors for OLNM in preoperative NSCLC patients. And establish a nomogram for OLNM in NSCLC patients before surgery. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the established nomogram., Result: Both univariate and multivariate logistic regression analyses suggested that multiple tumors, ERBB2 missense mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin are potential risk factors for OLNM in NSCLC patients. The constructed nomogram was evaluated, and the consistency index (C-index) and area under the ROC curve of the model were both 0.846. The calibration curve showed that the predicted values of the model had a high degree of fit with the actual observed values, and DCA suggested that the above indicators had good utility., Conclusion: The personalized scoring prediction model constructed based on multiple tumors, ERBB2 miss mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin can screen NSCLC patients who may have OLNM., (© 2024. The Author(s).)

The carboxysome is a natural proteinaceous organelle for carbon fixation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble to form a polyhedral shell structure to sequester cargo enzymes, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), and carbonic anhydrases. How these protein components assemble to construct a functional carboxysome is a central question in not only understanding carboxysome structure and function but also synthetic engineering of carboxysomes for biotechnological applications. Here, we determined the structure of the chaperone protein CcmS, which has recently been identified to be involved in β-carboxysome assembly, and its interactions with β-carboxysome proteins. The crystal structure at 1.99 Å resolution reveals CcmS from Nostoc sp. PCC 7120 forms a homodimer, and each CcmS monomer consists of five α-helices and four β-sheets. Biochemical assays indicate that CcmS specifically interacts with the C-terminal extension of the carboxysome shell protein CcmK1, but not the shell protein homolog CcmK2 or the carboxysome scaffolding protein CcmM. Moreover, we solved the structure of a stable complex of CcmS and the C-terminus of CcmK1 at 1.67 Å resolution and unveiled how the CcmS dimer interacts with the C-terminus of CcmK1. These findings allowed us to propose a model to illustrate CcmS-mediated β-carboxysome assembly by interacting with CcmK1 at the outer shell surface. Collectively, our study provides detailed insights into the accessory factors that drive and regulate carboxysome assembly, thereby improving our knowledge of carboxysome structure, function, and bioengineering., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

There are currently over forty degenerative diseases that are correlated with abnormal accumulation of peptide/protein aggregates in the human body, such as Alzheimer's disease. Due to their unique physiochemical properties (e.g., small size, large surface-to-volume ratio, and facile surface modification), silver nanoparticles (AgNPs) have been considered potential substrates for designing inhibitors against amyloid fibrillogenesis. Metal polyphenolic network (MPN) that combines the characteristics of organic and inorganic components has been used to suppress amyloid fibril formation. This study is aimed at investigating the effects of MPN-coated AgNPs (MPN-AgNPs) on the in vitro amyloid fibrillogenesis of hen lysozyme (HEWL). The two types of MPN-AgNPs (Zn/MPN-AgNPs and Co/MPN-AgNPs) were synthesized through chemical reduction and metal chelation, and their particle sizes were determined to be in the range of 40-60 nm. The characterization of MPN-AgNPs by ζ-potential and transmission electron microscopy showed that the MPN-AgNPs had negative surface charge and spherical-shaped morphology. Furthermore, the elemental analysis demonstrated that the MPN was uniformly coated on the surface of AgNPs. The thioflavin T fluorescence results revealed that the Co/MPN-AgNPs showed a better percent of inhibition compared to Zn/MPN-AgNPs and TA-AgNPs. The kinetics data of amyloid fibril formation in the presence of MPN-AgNPs were analyzed using the sigmoidal curve, showing that the MPN-AgNPs reduced fibril growth rate and prolonged lag time. Our findings also demonstrated that MPN-AgNPs could effectively suppress HEWL aggregation upon binding to aggregation-prone regions. The quenching of intrinsic fluorescence of HEWL by MPN-AgNPs was found to be a static type. Moreover, the fluorescence quenching data were analyzed using the modified Stern-Volmer equation to determine the number of binding sites. Notably, our findings indicated that the binding between HEWL and MPN-AgNPs was mainly governed by hydrophobic interaction. This work offers an excellent example of utilizing MPN-based materials as anti-aggregating/anti-fibrillogenic nano-drugs for the treatment of amyloidosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Numerous neurological disorders share a fatal pathologic process known as glutamate excitotoxicity. Among which, ischemic stroke is the major cause of mortality and disability worldwide. For a long time, the main idea of developing anti-excitotoxic neuroprotective agents was to block glutamate receptors. Despite this, there has been little successful clinical translation to date. After decades of "neuron-centered" views, a growing number of studies have recently revealed the importance of non-neuronal cells. Glial cells, cerebral microvascular endothelial cells, blood cells, and so forth are extensively engaged in glutamate synthesis, release, reuptake, and metabolism. They also express functional glutamate receptors and can listen and respond for fast synaptic transmission. This broadens the thoughts of developing excitotoxicity antagonists. In this review, the critical contribution of non-neuronal cells in glutamate excitotoxicity during ischemic stroke will be emphasized in detail, and the latest research progress as well as corresponding therapeutic strategies will be updated at length, aiming to reconceptualize glutamate excitotoxicity in a non-neuronal perspective., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuroinflammation and oxidative stress contribute to the progression of sepsis-associated encephalopathy (SAE). Angiotensin-converting enzyme 2 (ACE2) is considered to be a neuroprotective factor due to its anti-inflammatory and antioxidant properties. However, the role of ACE2 on myeloid cells in regulating SAE and the underlying mechanism warrants further exploration. SAE was induced in ACE2 transgenic (TG), knockout (KO), and bone marrow (BM) chimeric mice by cecal ligation and puncture (CLP). The expression levels of apoptosis-, oxidation- and neuroinflammation-associated mediators and morphological changes were monitored by quantitative real-time PCR analyses and histological examinations in the cortex of septic mice. The contents of angiotensin (Ang) II and Ang-(1-7) along with the activity of ACE2 were examined with commercial kits. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2 was detected by immunoblotting analysis. Our results indicated that the expression of cortical ACE2 was significantly reduced in the early phase of CLP-induced sepsis. Moreover, ACE2 overexpression in TG mice conferred neuroprotection against sepsis, as evidenced by alleviated neuronal apoptosis, oxidative stress, and proinflammatory M1-like microglial polarization, accompanied by upregulation of the Ang-(1-7), Nrf2, and Sestrin2 protein levels. Conversely, ACE2 deficiency in KO mice exacerbated SAE. The neuroprotective effects of ACE2 were further confirmed in wild-type mice transplanted with ACE2-TG and KO BM cells. Therefore, our data suggest that myeloid ACE2 exerts a protective role in the pathogenesis of SAE, potentially by activating Ang-(1-7)-Nrf2/sestrin2 signaling pathway, and highlight that upregulating ACE2 expression and activity may represent a promising approach for the treatment of SAE in patients with sepsis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As concerns about environmental pollution grow, the rapid identification and quantification of pollutants have become increasingly vital. In this work, a series of pyrimidine derivatives-Cu enzyme mimics (Cytosine-Cu, Cytidine-Cu, and CMP-Cu) with laccase- and peroxidase-like activity were prepared through the coordination of Cu 2+ with different pyrimidine derivatives (PDs). The PDs-Cu enzyme mimics contain high levels of Cu + and N - Cu coordination structures, which provide sufficient catalytic sites for the substrates. Compared with natural enzymes and other nanozymes, PDs-Cu demonstrate superior substrate affinity, catalytic efficiency, stability, and resistance to interference. It was found that PDs-Cu enzyme mimics have different catalytic activities towards different phenolic compounds. Therefore, a three-channel colorimetric sensor array (CSA) was successfully developed utilizing PDs-Cu as the sensing elements. The CSA can accurately identify different phenolic compounds and their mixtures in seawater and simulated wastewater. Additionally, a colorimetric method for detecting H 2 O 2 in eye drops was developed, featuring a detection range of 0.1-10.0 μM and a limit of quantification of 0.1 μM. This research not only provides a flexible protocol for regulating the catalytic activity of enzyme mimics, but also provides important inspiration for the development of methods for rapid identification and detection of contaminants in the environmental water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest The authors all have read and approved the present manuscript, and declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Guidelines advise automated office blood pressure (AOBP) with an initial 5-minute delay and multiple measurements at least 60 seconds apart. Recent studies suggest that AOBP may be accurate with shorter delays or intervals, but evidence in clinical settings is limited., Methods: Patients referred to one hypertension (HTN) center underwent 24-hour ambulatory blood pressure monitoring (ABPM) and one of four non-randomized, unattended AOBP protocols: a 3- or 5-minute delay with a 30 or 60-second interval, i.e., 3 min/30 sec/30 sec, 3/60/60, 5/30/30 and 5/60/60 protocols. HTN was defined as systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg., Results: We compared differences in mean blood pressure and HTN classification between average AOBP and awake-time ABPM by t-tests and Fisher's exact test. Among 212 participants (mean 58.9 years, 61% women, 25% Black), there was substantial overlap in the probability distributions of awake-time ABPM and each of the three AOBP measures. Systolic blood pressure means were similar between the 5/60/60 and 3/30/30 protocols and 5/30/30 and 3/60/60 protocols. The 5/30/30 was associated with a higher proportion of systolic HTN, while the 3/60/60 protocol was associated with a higher proportion of diastolic HTN. There were no significant differences in systolic or diastolic HTN between 5/60/60 and 3/30/30 protocols with respect to awake-time ABPM., Conclusions: In this quality improvement study, the shortest AOBP protocol did not differ significantly from the longest protocol. The time savings of shorter protocols may improve AOBP adoption in clinical practice without meaningfully compromising accuracy., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because of their extensive use as saturated bioisosteres of arene in pharmaceutical industry. However, in sharp contrast to their racemic counterparts, assembling chiral bridged bicyclic structures in an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing chiral 2-oxa-3-azabicyclo[3.1.1]heptanes (BCHeps) by enantioselective [4π + 2σ] cycloadditions of bicyclo[1.1.0]butanes (BCBs) and nitrones taking advantage of a chiral copper(II) complex as a Lewis acid catalyst. This method features mild conditions, good functional group tolerance, high yield (up to 99%), and excellent enantioselectivity (up to 99% ee). Density functional theory (DFT) calculation elucidates the origin of the reaction's enantioselectivity and the mechanism of BCB activation by Cu(II) complex.

Directly converting CO 2 in flue gas using artificial photosynthetic technology represents a promising green approach for CO 2 resource utilization. However, it remains a great challenge to achieve efficient reduction of CO 2 from flue gas due to the decreased activity of photocatalysts in diluted CO 2 atmosphere. Herein, we designed and synthesized a series of dual metallosalen-based covalent organic frameworks (MM-Salen-COFs, M: Zn, Ni, Cu) for artificial photosynthetic diluted CO 2 reduction and confirmed their advantage in comparison to that of single metal M-Salen-COFs. As a results, the ZnZn-Salen-COF with dual Zn sites exhibits a prominent visible-light-driven CO 2 -to-CO conversion rate of 150.9 μmol g -1  h -1 under pure CO 2 atmosphere, which is ~6 times higher than that of single metal Zn-Salen-COF. Notably, the dual metal ZnZn-Salen-COF still displays efficient CO 2 conversion activity of 102.1 μmol g -1  h -1 under diluted CO 2 atmosphere from simulated flue gas conditions (15 % CO 2 ), which is a record high activity among COFs- and MOFs-based photocatalysts under the same reaction conditions. Further investigations and theoretical calculations suggest that the synergistic effect between the neighboring dual metal sites in the ZnZn-Salen-COF facilitates low concentration CO 2 adsorption and activation, thereby lowering the energy barrier of the rate-determining step., (© 2024 Wiley-VCH GmbH.)

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1 -/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3β (Gsk3β) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Uncontrollable interfacial side reactions generated from common aqueous electrolytes, just like the hydrogen evolution reaction (HER) and dendrite growth, have severely prevented the practical application of zinc-ion batteries (ZIBs). Solid-state ZIBs are considered to be an efficient strategy by adopting high-quality solid-state electrolytes (SSEs). Here, by confining deep eutectic electrolyte (DEE) into the nanochannels of metal-organic framework (MOF)-PCN-222, a stable DEE@PCN-222 SSE with internal Zn 2+ transport channels was obtained. A distinctive ion-transport network composed of DEE and PCN-222 in the interior of DEE@PCN-222 realizes the efficient Zn 2+ conduction, contributing to high ionic conductivity of 3.13×10 -4  S cm -1 at room temperature, low activation energy of 0.12 eV, and a high Zn 2+ transference number of 0.74. Furthermore, experimental and theoretical investigations demonstrate that DEE@PCN-222 with its unique channel structure could homogeneously regulate the Zn 2+ distribution and effectively alleviate the side reactions. Highly reversible Zn plating/stripping performance of 2476 h can be realized by the SSE. The solid-state ZIBs show a specific capacity of 306 mAh g -1 and display cycling stability of 517 cycles. This unique design concept provides a new perspective in realizing the high-safety and high-performance ZIBs., (© 2024 Wiley-VCH GmbH.)

Trace amine-associated receptor 1 (TAAR1) negatively modulates monoaminergic transmission in the mammalian brain and participates in many psychiatric disorders. Preclinical evidence indicate that selective TAAR1 agonists have anxiolytic effects and anti-stress properties. Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by experiencing or witnessing traumatic stressors. However, it remains unknown whether TAAR1 is involved in PTSD. Here, we investigated the role of TAAR1 in two PTSD animal models, including single prolonged stress (SPS)-induced impairment of fear extinction and stress-enhanced fear learning (SEFL). SPS decreased TAAR1 mRNA levels in the prefrontal cortex and ventral tegmental area. Acute treatment of the TAAR1 partial agonist RO5263397 attenuated SPS-induced anxiety-like behavior evaluated by the elevated-plus maze test. Compared to non-stressed animals, rats that experienced SPS showed higher freezing levels in the extinction retention test, indicating an impairment of fear extinction retention after SPS exposure. Acute and chronic treatment of RO5263397 ameliorated SPS-induced impairment of fear extinction retention. In the SEFL model, compared to the No-shock group, rats that experienced severe foot shock before fear conditioning showed higher freezing levels during the tests, indicating enhanced fear learning after stress exposure. Chronic treatment of RO5263397 partially attenuated the SEFL. Moreover, chronic treatment with the selective TAAR1 full agonist RO5166017 completely prevented the SEFL. Taken together, these data showed that pharmacological activation of TAAR1 could ameliorate PTSD-like symptoms. The present study thus provides the first evidence that TAAR1 might participate in the development of PTSD, and TAAR1 agonists could be potential pharmacological treatments for this disorder., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by STI2030-Major Projects (2022ZD0207100) and Natural Science Foundation of China (No. 82171490) to Dr. Jianfeng Liu. The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Uterine Fibroids (UFs) are common benign tumors in the female reproductive tract, but their progression to intravascular leiomyomatosis (IVL) is rare. Presently, there are few reports on single-stage resection of UFs and IVL., Case Presentation: A 47-year-old woman, G2P2, had been diagnosed multiple UFs four years ago and now developed heart failure. Imaging examinations revealed that UFs had invaded the right iliac vein and extended into the right atrium through the inferior vena cava. Through multidisciplinary collaboration and a single-stage resection, the patient has survived for over 24 months post-surgery, and her heart function has significantly improved compared to preoperative levels, with no recurrence of UFs observed., Conclusions: Single-stage resection of IVL and UF is feasible and advantageous for this case, and selecting the appropriate surgical approach is crucial., (© 2024. The Author(s).)

Angiotensin-converting enzyme 2 (ACE2), a crucial element of the renin-angiotensin system (RAS), metabolizes angiotensin II into Ang (1-7), which then combines with the Mas receptor (MasR) to fulfill its protective role in various diseases. Nevertheless, the involvement of ACE2 in sepsis-induced cardiomyopathy (SIC) is still unexplored. In this study, our results revealed that CLP surgery dramatically impaired cardiac function accompanied with disruption of the balance between ACE2-Ang (1-7) and ACE-Ang II axis in septic heart tissues. Moreover, ACE2 knockin markedly alleviated sepsis induced RAS disorder, cardiac dysfunction and improved survival rate in mice, while ACE2 knockout significantly exacerbates these outcomes. Adoptive transfer of bone marrow cells and in vitro experiments showed the positive role of myeloid ACE2 by mitigating oxidative stress, inflammatory response, macrophage polarization and cardiomyocyte apoptosis by blocking NF-κB and STAT1 signals. However, the beneficial impacts were nullified by MasR antagonist A779. Collectively, these findings showed that ACE2 alleviated SIC by inhibiting M1 macrophage via activating the Ang (1-7)-MasR axis, highlight that ACE2 might be a promising target for the management of sepsis and SIC patients., (© 2024. The Author(s).)

Objective: To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China, and provide the basis for formulating prevention and control measures., Methods: Fixed-point monitoring, moving-point monitoring, and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria, clinical and X-ray assessments were used to confirm the diagnosis., Results: In 1990, the national KBD detectable rate was 21.01%. X-ray detection decreased to below 10% in 2003 and below 5% in 2007. Between 2010 and 2018, the prevalence of KBD in children was less than 0.4%, which fluctuated at a low level, and has decreased to 0% since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas., Conclusion: The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Bacteria are becoming an increasingly serious threat to human health. The emergence of super bacteria makes clinical treatment more difficult. Vaccines are one of the most effective means of preventing and treating bacterial infections. As a new class of vaccines, killed but metabolically active (KBMA) vaccines provide the immunogenicity of live vaccines and the safety of inactivated vaccines. Herein, a promising strategy is proposed to improve the stability and immunogenicity of KBMA vaccines. KBMA vaccines were produced at low temperature (4 °C), and the bacterial surface was engineered using mesoporous silica nanoparticle (MSN) coating. Compared to vaccines prepared at room temperature, the metabolic activity of KBMA vaccines prepared at 4 °C remarkably improved. Benefiting from the induction of MSNs, the stability of KBMA vaccines was increased and the preservation time was prolonged at 4 °C. Meanwhile, metabolomics analysis showed that the metabolite spectrum of live bacteria changed after photochemical treatment and MSN coating, which interfered with organic acid metabolism pathways, lipid metabolism and biosynthesis of secondary metabolites. Furthermore, the immune response in the mice treated with KBMA/MSN vaccines was similar to that in those treated with live vaccines and stronger than that in those treated with inactivated vaccines. In comparison with the control group, bacteria tissue burdens of KBMA/MSN group were significantly reduced. CD4 + T cells dominated immune responses for the protection of mice. Thus, the current work promotes the application of KBMA vaccines, providing an alternative choice for treating bacterial infections.

Transition metal oxides ion diffusion channels have been developed for ammonium-ion batteries (AIBs). However, the influence of microstructural features of diffusion channels on the storage and diffusion behavior of NH 4 + is not fully unveiled. In this study, by using MnCo 2 O 4 spinel as a model electrode, the asymmetric ion diffusion channels of MnCo 2 O 4 have been regulated through bond length optimization strategy and investigate the effect of channel size on the diffusion process of NH 4 + . In addition, the reducing channel size significantly decreases NH 4 + adsorption energy, thereby accelerating hydrogen bond formation/fracture kinetics and NH 4 + reversible diffusion within 3D asymmetric channels. The optimized MnCo 2 O 4 with oxygen vacancies/carbon nanotubes composite exhibits impressive specific capacity (219.2 mAh g -1 at 0.1 A g -1 ) and long-cycle stability. The full cell with 3,4,9,10-perylenetetracarboxylic diimide anode demonstrates a remarkable energy density of 52.3 Wh kg -1 and maintains 91.9% capacity after 500 cycles. This finding provides a unique approach for the development of cathode materials in AIBs., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: To compare therapeutic outcomes of predicted proliferative and nonproliferative hepatocellular carcinoma (HCC) after microwave ablation (MWA) using a previously developed imaging-based predictive model, the SMARS score., Methods: This multicenter retrospective study included consecutive 635 patients with unresectable HCC who underwent MWA between August 2013 and September 2020. Patients were stratified into predicted proliferative and nonproliferative phenotypes according to the SMARS score. Overall survival (OS) and recurrence-free survival (RFS) were compared between the predicted proliferative and nonproliferative HCCs before and after propensity score matching (PSM). OS and RFS were also compared between the two groups in subgroups of tumor size smaller than 30 mm and tumor size 30-50 mm., Results: The SMARS score classified 127 and 508 patients into predicted proliferative and nonproliferative HCCs, respectively. The predicted proliferative HCCs exhibited worse RFS but equivalent OS when compared with nonproliferative HCCs before (p < 0.001 for RFS; p = 0.166 for OS) and after (p < 0.001 for RFS; p = 0.456 for OS) matching. Regarding subgroups of tumor size smaller than 30 mm (p = 0.098) and tumor size 30-50 mm (p = 0.680), the OSs were similar between the two groups. However, predicted proliferative HCCs had worse RFS compared to nonproliferative HCCs in the subgroup of tumor size 30-50 mm (p < 0.001), while the RFS did not differ in the subgroup of tumor size smaller than 30 mm (p = 0.141)., Conclusion: Predicted proliferative HCCs have worse RFS than nonproliferative ones after MWA, especially in tumor size larger than 30 mm. However, the phenotype of the tumor may not affect the OS., Critical Relevance Statement: Before performing microwave ablation for hepatocellular carcinoma, the tumor phenotype should be considered because it may affect the therapeutic outcome., Key Points: Proliferative hepatocellular carcinoma (HCC) may be identified using the SMARS score, an imaging-based predictive model. SMARS predicted proliferative HCCs have worse recurrence-free and equivalent overall survival compared to nonproliferative HCC after microwave ablation. Tumor phenotype should be considered before performing microwave ablation., (© 2024. The Author(s).)

Background: Santalum album L. is an evergreen tree which is mainly distributes throughout tropical and temperate regions. And it has a great medicinal and economic value., Results: In this study, the complete mitochondrial genome of S. album were assembled and annotated, which could be descried by a complex branched structure consisting of three contigs. The lengths of these three contigs are 165,122 bp, 93,430 bp and 92,491 bp. We annotated 34 genes coding for proteins (PCGs), 26 tRNA genes, and 4 rRNA genes. The analysis of repeated elements shows that there are 89 SSRs and 242 pairs of dispersed repeats in S. album mitochondrial genome. Also we found 20 MTPTs among the chloroplast and mitochondria. The 20 MTPTs sequences span a combined length of 22,353 bp, making up 15.52 % of the plastome, 6.37 % of the mitochondrial genome. Additionally, by using the Deepred-mt tool, we found 628 RNA editing sites in 34 PCGs. Moreover, significant genomic rearrangement is observed between S. album and its associated mitochondrial genomes. Finally, based on mitochondrial genome PCGs, we deduced the phylogenetic ties between S. album and other angiosperms., Conclusions: We reported the mitochondrial genome from Santalales for the first time, which provides a crucial genetic resource for our study of the evolution of mitochondrial genome., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This article describes the case of a 40-year-old individual who presented with fulminant myocarditis. Initial ECG displayed sinus tachycardia with a heart rate of 117 bpm, QS complexes in leads V1-V3, ST-segment depression in leads II, III, aVF, V5-V6, and ST-segment elevation >0.2 mV in leads V1 through V3. The initial clinical assessment suggested an acute anteroseptal myocardial infarction. However, subsequent diagnostic evaluation through coronary angiography disclosed that the coronary arteries were normal. Therefore, clinicians should carefully consider the differential diagnosis between these conditions, as their management strategies differ markedly. Two hours after admission, the patient unexpectedly developed syncope. The ECG findings were consistent with the typical characteristics of bidirectional ventricular tachycardia. Our report described the appearance and morphology as well as mechanism of bidirectional ventricular tachycardia in detail. Additionally, we delineate differential diagnoses for disease that can cause bidirectional ventricular tachycardia, such as aconite poisoning, digoxin overdose, immune checkpoint inhibitor (ICI), myocardial ischemia, and hereditary channelopathies, such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and Andersen-Tawil syndrome. Therefore, clinicians should recognize this ECG finding immediately and initiate appropriate treatment promptly as these measures may be vital in saving the patient's life., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear., Objectives: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012., Methods: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data., Results: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations., Conclusions: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism., Methods: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells., Results: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PD‑L1 of A549 cells stimulated by IFN‑γ as well., Conclusion: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Ethnopharmacological Relevance: Cimicifuga heracleifolia Kom. (C. heracleifolia) has demonstrated efficacy in treating gastrointestinal disorders, including splenasthenic diarrhea. Ulcerative colitis (UC), a chronic inflammatory bowel disease, shares similarities with splenasthenic diarrhea. However, the pharmacological effects of C. heracleifolia on UC and the underlying mechanisms remain unexplored., Aim of the Study: The present study investigates the therapeutic potential and mechanisms of C. heracleifolia in UC., Methods: Initially, network pharmacology analysis, encompassing ingredient screening, target prediction, protein-protein interaction (PPI) network analysis, and enrichment analysis, was employed to predict the mechanisms of C. heracleifolia. The findings were further validated using transcriptomics and functional assays in a dextran sulfate sodium (DSS)-induced UC model. Additionally, bioactive compounds were identified through surface plasmon resonance (SPR) analysis, molecular docking, and cell-based assays., Results: A total of 52 ingredients of C. heracleifolia were screened, and 32 key targets were identified within a PPI network comprising 285 potential therapeutic targets. Enrichment analysis indicated that the anti-UC effects of C. heracleifolia are mediated through immune response modulation and the inhibition of inflammatory signaling pathways. In vivo experiments showed that C. heracleifolia mitigated histological damage in the colon, reduced the expression of phosphorylated Akt1, nuclear factor-kappa B (NF-κB) p65, and inhibitor of Kappa B kinase α/β (IKKα/β), suppressed the content of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and enhanced the expression of tight junction proteins. Moreover, cimigenoside, caffeic acid, and methyl caffeate were identified as the bioactive constituents responsible for the UC treatment effects of C. heracleifolia., Conclusions: In summary, this study is the first to demonstrate that C. heracleifolia exerts therapeutic effects on UC by enhancing the intestinal mucosal barrier and inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/NF-κB signaling pathway. These findings offer valuable insights into the clinical application of C. heracleifolia for UC management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The detailed characterization of the structural features of peptides targeting cholesterol esterase (CEase) or pancreatic lipase (PPL) will benefit the management of hyperlipidemia and obesity. This study employed the Glide SP (standard precision)-peptide method to predict the binding modes of 20 2 dipeptides and 20 3 tripeptides to these targets, correlating residue composition and position with binding energy. Strong preferences for Trp, Phe, and Tyr were observed at all positions of potential inhibitory peptides, whereas negatively charged residues Glu and Asp were disfavored. Notably, Arg and aromatic rings significantly influenced the peptide conformation at the active site. Tripeptide IWR demonstrated the high efficacy, with IC 50 values of 0.214 mg/mL for CEase and 0.230 mg/mL for PPL. Five novel IWR scaffold-tetrapeptides exhibited promising inhibitory activity. Non-covalent interactions and energy contributions dominated the formation of stable complexes. Our results provide insights for the development of new sequences or peptide-like molecules with enhanced inhibitory activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Acute kidney injury (AKI) is a common disease, but lacking effective drug treatments. Chromodomain Y-like (CDYL) is a kind of chromodomain protein that has been implicated in transcription regulation of autosomal dominant polycystic kidney disease. Benzo[d]oxazol-2(3H)-one derivative (compound D03) is the first potent and selective small-molecule inhibitor of CDYL (K D  = 0.5 μM). In this study, we investigated the expression of CDYL in three different models of cisplatin (Cis)-, lipopolysaccharide (LPS)- and ischemia/reperfusion injury (IRI)-induced AKI mice. By conducting RNA sequencing and difference analysis of kidney samples, we found that tubular CDYL was abnormally and highly expressed in injured kidneys of AKI patients and mice. Overexpression of CDYL in cisplatin-induced AKI mice aggravated tubular injury and pyroptosis via regulating fatty acid binding protein 4 (FABP4)-mediated reactive oxygen species production. Treatment of cisplatin-induced AKI mice with compound D03 (2.5 mg·kg -1 ·d -1 , i.p.) effectively attenuated the kidney dysfunction, pathological damages and tubular pyroptosis without side effects on liver or kidney function and other tissue injuries. Collectively, this study has, for the first time, explored a novel aspect of CDYL for tubular epithelial cell pyroptosis in kidney injury, and confirmed that inhibition of CDYL might be a promising therapeutic strategy against AKI., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Motivated by very recent experimental observations of the 1/9-magnetization plateaus in YCu&#95;{3}(OH)&#95;{6+x}Br&#95;{3-x} and YCu&#95;{3}(OD)&#95;{6+x}Br&#95;{3-x}, our study delves into the magnetic-field-induced phase transitions in the nearest-neighbor antiferromagnetic Heisenberg model on the kagome lattice using the variational Monte Carlo technique. We uncover a phase transition from a zero-field Dirac spin liquid to a field-induced magnetically disordered phase that exhibits the 1/9-magnetization plateau. Through a comprehensive analysis encompassing the magnetization distribution, spin correlations, chiral order parameter, topological entanglement entropy, ground-state degeneracy, Chern number, and excitation spectrum, we pinpoint the phase associated with this magnetization plateau as a chiral Z&#95;{3} topological quantum spin liquid and elucidate its diverse physical properties.

Objective: This study was designed to reveal the role of nuclear poly(A) binding protein 1 (PABPN1) in the proliferation of preadipocytes, and to reveal the relationship between PABPN1 and cAMP response element (CRE)-binding protein (CREB) in the regulation of preadipocyte proliferation., Methods: Vectors overexpressing and siRNAs against PABPN1/CREB were transiently transfected into both porcine preadipocytes and mouse 3T3-L1 cells. Preadipocyte proliferation was measured with CCK-8, EdU, real-time quantitative PCR, Western blotting, and flow cytometry analyses. Additionally, the transcriptional regulation of CREB on PABPN1 were analyzed with dual-luciferase reporter gene and EMSA assays., Results: Overexpression of PABPN1 inhibits, and knockdown of PABPN1 promotes, the proliferation of both porcine preadipocytes and 3T3-L1 cell lines. PABPN1 overexpression increased, while knockdown decreased, the cell population in the G0/G1 phase. These indicates that PABPN1 repressed preadipocyte proliferation by inhibiting cell cycle progress. Additionally, it was revealed that CREB regulated the expression of PABPN1 through binding to the promoter and that CREB inhibited preadipocyte proliferation by repressed cell cycle progress. Furthermore, we showed that PABPN1 functions as a downstream gene of CREB to regulate the proliferation of preadipocytes., Conclusion: PABPN1 inhibits preadipocyte proliferation by suppressing the cell cycle. We also found that CREB could promote PABPN1 expression by binding to a motif in the promoter. Further analysis confirmed that PABPN1 functions as a downstream gene of CREB to regulate the proliferation of preadipocytes. These results suggest that the CREB/PABPN1 axis plays a role in the regulation of preadipocyte proliferation, which will contribute to further revealing the mechanism of fat accumulation.

Background: Systemic inflammation and nutrition play pivotal roles in cancer progression and can increase the risk of delayed recovery after surgical procedures., Aim: To assess the significance of inflammatory and nutritional indicators for the prognosis and postoperative recovery of patients with pancreatic cancer (PC)., Methods: Patients who were diagnosed with PC and underwent surgical resection at our hospital between January 1, 2019, and July 31, 2023, were enrolled in this retrospective observational cohort study. All the data were collected from the electronic medical record system. Seven biomarkers - the albumin-to-globulin ratio, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), nutritional risk index (NRI), and geriatric NRI were assessed., Results: A total of 446 patients with PC met the inclusion criteria and were subsequently enrolled. Patients with early postoperative discharge tended to have higher PNI values and lower SII, NLR, and PLR values (all P < 0.05). Through multivariable logistic regression analysis, the SII value emerged as an independent risk factor influencing early recovery after surgery. Additionally, both univariable and multivariable Cox regression analyses revealed that the PNI value was the strongest prognostic marker for overall survival (OS; P = 0.028) and recurrence-free survival (RFS; P < 0.001). The optimal cutoff PNI value was established at 47.30 using X-tile software. Patients in the PNI-high group had longer OS ( P < 0.001) and RFS ( P = 0.0028) times than those in the PNI-low group., Conclusion: Preoperative systemic inflammatory-nutritional biomarkers may be capable of predicting short-term recovery after surgery as well as long-term patient outcomes., Competing Interests: Conflict-of-interest statement: All authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: In recent decades, China has implemented a series of policies to address air pollution. We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter (PM 2.5 )., Methods: Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study., Results: The age-standardized rates of disability-adjusted life year (DALY) for stroke attributable to ambient PM 2.5 in China, increased dramatically during 1990-2012, subsequently decreased at an annual percentage change (APC) of -1.98 [95% confidence interval ( CI ): -2.26, -1.71] during 2012-2019. For ischemic stroke (IS), the age-standardized DALY rates doubled from 1990 to 2014, and decreased at an APC of -0.83 (95% CI : -1.33, -0.33) during 2014-2019. Intracerebral hemorrhage (ICH) showed a substantial increase in age-standardized DALY rates from 1990 to 2003, followed by declining trends, with APCs of -1.46 (95% CI : -2.74, -0.16) during 2003-2007 and -3.33 (95% CI : -3.61, -3.06) during 2011-2019, respectively. Conversely, the age-standardized DALY rates for subarachnoid hemorrhage (SAH) generally declined during 1990-2019., Conclusion: Our results clarified the dynamic changes of the ambient PM 2.5- attributable stroke burden in China during 1990-2019, highlighting the health effects of air quality improvement policies., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)