A review on Pd-M bimetallic electrochemical sensors: Techniques, performance, and applications.

Environmental pollution, food safety, and medical diagnostics pose severe threats to human health, making the development of effective detection technologies crucial. Electrochemical sensors, as an efficient detection method, are extensively employed in detecting environmental pollutants, food additives, and biomolecules. Pd-M bimetallic materials, known for their excellent electrocatalytic performance, are extensively utilized as electrode modification materials. Although earlier reviews have covered the sensing applications of bimetallic materials, they have not targeted discussed Pd-based bimetallic materials. This paper systematically summarizes the preparation methods of Pd-M bimetallic materials, explores their structural and morphological regulation, and elaborates on their recent applications in pesticide detection, environmental pollutant detection, food additive detection, drug detection, and biosensing. It enumerates the detection performance of various Pd-M bimetallic material-modified electrochemical sensors for the aforementioned analytes in detail, including specific modification materials, linear range, detection limits, and sensitivity parameters.

Bile acids as signaling molecules in inflammatory bowel disease: Implications for treatment strategies.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is a globally increasing disease. Despite continuous efforts, the clinical application of treatment drugs has not achieved satisfactory success and faces limitations such as adverse drug reactions. Numerous investigations have found that the pathogenesis of IBD is connected with disturbances in bile acid circulation and metabolism. Traditional Chinese medicine targeting bile acids (BAs) has shown significant therapeutic effects and advantages in treating inflammatory bowel disease. AIM OF THIS REVIEW: IThis article reviews the role of bile acids and their receptors in IBD, as well as research progress on IBD therapeutic drugs based on bile acids. It explores bile acid metabolism and its interaction with the intestinal microbiota, summarizes clinical drugs for treating IBD including single herbal medicine, traditional herbal prescriptions, and analyzes the mechanisms of action in treating IBD. MATERIALS AND METHODS: IThe electronic databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) have been utilized to retrieve relevant literature up to January 2024, using keywords "bile acid", "bile acid receptor", "inflammatory bowel disease", "intestinal microbiota" and "targeted drugs". RESULTS: IImbalance in bile acid levels can lead to intestinal inflammation, while IBD can disrupt the balance of microbes, result in alterations in the bile acid pool's composition and amount. This change can damage of intestinal mucosa healing ability. Bile acids are vital for keeping the gut barrier function intact, regulating gene expression, managing metabolic equilibrium, and influencing the properties and roles of the gut's microbial community. Consequently, focusing on bile acids could offer a potential treatment strategy for IBD. CONCLUSION: IIBD can induce intestinal homeostasis imbalance and changes in BA pool, leading to fluctuations in levels of relevant metabolic enzymes, transporters, and nuclear receptors. Therefore, by regulating the balance of BA and key signaling molecules of bile acids, we can treat IBD. Traditional Chinese medicine has great potential and promising prospects in treating IBD. We should focus on the characteristics and advantages of Chinese medicine, promote the development and clinical application of innovative Chinese medicine, and ultimately make Chinese medicine targeting bile acids the mainstream treatment for IBD.

Ferroptosis: A New Strategy for the Treatment of Fibrotic Diseases.

Ferroptosis is a new type of cell death characterized by iron dependence and the excessive accumulation of lipid reactive oxygen species (lipid ROS) that has gradually become better characterized. There is sufficient evidence indicating that ferroptosis is associated with a variety of human life activities and diseases, such as tumor suppression, ischemic organ injury, and degenerative disorders. Notably, ferroptosis is also involved in the initiation and development of fibrosis in various organs, including liver fibrosis, pulmonary fibrosis, renal fibrosis, and cardiac fibrosis, which is usually irreversible and refractory. Although a large number of patients with fibrosis urgently need to be treated, the current treatment options are still limited and unsatisfactory. Organ fibrosis involves a series of complex and orderly processes, such as parenchymal cell damage, recruitment of inflammatory cells and activation of fibroblasts, which ultimately leads to the accumulation of extracellular matrix (ECM) and the formation of fibrosis. An increasing number of studies have confirmed the close association between these pathological processes and ferroptosis. This review summarizes the role and function of ferroptosis in fibrosis and proposes several potential therapeutic strategies and pathways based on ferroptosis.

CT-based conventional radiomics and quantification of intratumoral heterogeneity for predicting benign and malignant renal lesions.

BACKGROUND: With the increasing incidence of renal lesions, pretreatment differentiation between benign and malignant lesions is crucial for optimized management. This study aimed to develop a machine learning model utilizing radiomic features extracted from various regions of interest (ROIs), intratumoral ecological diversity features, and clinical factors to classify renal lesions. METHODS: CT images (arterial phase) of 1,795 renal lesions with confirmed pathology from three hospital sites were split into development (1184, 66%) and test (611, 34%) cohorts by surgery date. Conventional radiomic features were extracted from eight ROIs of arterial phase images. Intratumoral ecological diversity features were derived from intratumoral subregions. The combined model incorporating these features with clinical factors was developed, and its performance was compared with radiologists' interpretation. RESULTS: Combining intratumoral and peritumoral radiomic features, along with ecological diversity features yielded the highest AUC of 0.929 among all combinations of features extracted from CT scans. After incorporating clinical factors into the features extracted from CT images, our combined model outperformed the interpretation of radiologists in the whole (AUC = 0.946 vs 0.823, P < 0.001) and small renal lesion (AUC = 0.935 vs 0.745, P < 0.001) test cohorts. Furthermore, the combined model exhibited favorable concordance and provided the highest net benefit across threshold probabilities exceeding 60%. In the whole and small renal lesion test cohorts, the AUCs for subgroups with predicted risk below or above 95% sensitivity and specificity cutoffs were 0.974 and 0.978, respectively. CONCLUSIONS: The combined model, incorporating intratumoral and peritumoral radiomic features, ecological diversity features, and clinical factors showed good performance for distinguishing benign from malignant renal lesions, surpassing radiologists' diagnoses in both whole and small renal lesions. It has the potential to save patients from unnecessary invasive biopsies/surgeries and to enhance clinical decision-making.

Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration.

BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.

Yangzheng mixture reversed EMT against hepatocellular carcinoma metastasis via NF-κB/NLRP3/ß-catenin pathway.

Yangzheng mixture has been used as an adjuvant tumor therapy as a traditional Chinese medicine in clinical. However, less is known about the activity of Yangzheng mixture. In our study, we explored the anti-tumor activity of Yangzheng mixture for HCC in vitro and in vivo. The effects of Yangzheng mixture on HCC biological behaviors were assessed using colony formation assay, EdU staining, cell cycle assay, Annexin V/PI staining, and wound healing assay. Migration and invasion of HCC cells were further evaluated via transwell assays, while molecular mechanisms were investigated through western blotting and immunofluorescence staining. Additionally, the anticancer effect of Yangzheng mixture in vivo were examined using H22 xenograft and H22 metastatic hepatocellular carcinoma models. Our results revealed that Yangzheng mixture inhibited colony formation, EdU incorporation, cell migration, and invasion, while arresting cell cycle at the G2-M phase in Bel-7402 and SMMC-7721 cells. Mechanistic studies demonstrated that Yangzheng mixture showed a markedly inhibition on Bel-7402 and SMMC-7721 cells with higher NLRP3 expression. We further confirmed that Yangzheng mixture could activate NLRP3 inflammasome through NF-κB by western blotting and immunofluorescence staining. Additionally, Yangzheng mixture inhibited ß-catenin nucleus translocation and reversed EMT process. In vivo, the H22 xenograft model depicted that Yangzheng mixture significantly reduced tumor size and weight compared with control. Moreover, H22 lung metastasis model showed that Yangzheng mixture significantly inhibited liver cancer cell spreading to lungs in mice. Overall, our finding revealed that Yangzheng mixture inhibited HCC proliferation and migration in vitro and in vivo by reversing EMT via NF-κB/NLRP3/ß-catenin pathway. These results may serve new therapeutic evidences for Yangzheng mixture application in clinical.

Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease.

Although autosomal-dominant inheritance is believed an important cause of familial clustering Alzheimer's disease (FAD), it covers only a small proportion of FAD incidence, and so we investigated epigenetic memory as an alternative mechanism to contribute for intergenerational AD pathogenesis. Our data in vivo showed that mys-2 of Caenorhabditis elegans that encodes a putative MYST acetyltransferase responsible for H4K16 acetylation modulated AD occurrence. The phenotypic improvements in the parent generation caused by mys-2 disfunction were passed to their progeny due to epigenetic memory, which resulted in similar H4K16ac levels among the candidate target genes of MYS-2 and similar gene expression patterns of the AD-related pathways. Furthermore, the ROS/CDK-5/ATM pathway functioned as an upstream activator of MYS-2. Our study indicated that MYS-2/MOF could be inherited intergenerationally via epigenetic mechanisms in C. elegans and mammalian cell of AD model, providing a new insight into our understanding of the etiology and inheritance of FAD.

Contrast-enhanced intraoperative ultrasound improved hepatic recurrence-free survival in initially unresectable colorectal cancer liver metastases.

BACKGROUND: We aimed to evaluate the role of Contrast-enhanced intraoperative ultrasound (CE-IOUS) with perfluorobutane microbubbles (Sonazoid) in improving the prognosis of patients with unresectable colorectal cancer liver metastases (CRLM). METHODS: A total of 130 Patients with unresectable CRLM who underwent curative hepatic resection at our institute were retrospectively analyzed. Of these 130 enrolled patients, 67 underwent intraoperative ultrasound alone (IOUS group); 63 underwent additional CE-IOUS and IOUS (CE-IOUS group). Normalized inverse probability treatment weighting (IPTW) was employed to balance baseline characteristics between groups. Hepatic recurrence-free survival (HRFS) and overall survival (OS) were compared. RESULTS: The treatment strategy was altered in 25 patients (25/63, 39.9%) due to the additional use of CE-IOUS. After applying IPTW, the CE-IOUS group exhibited a significantly lower rate of hepatic recurrence (hazard ratio [HR], 0.55; 95% confidence interval [CI] 0.32-0.95; P = 0.032). Subgroup analysis showed that CE-IOUS provided a significant benefit over IOUS in patients with bilobar liver metastases (P = 0.007), or with a number of live tumors < 3 (P = 0.021), or without DLM (P = 0.018), or with extrahepatic metastasis (P = 0.034), or with a minimum of 6 cycles of systemic therapy (P = 0.03). CONCLUSIONS: CE-IOUS is necessary for unresectable CRLM after preoperative chemotherapy, as it enhances detection accuracy and improves the prognosis of unresectable CRLM patients.

Bimetallic PdCu anchored to 3D flower-like carbon material for portable and efficient detection of glyphosate.

Glyphosate (Gly), as a widely used broad-spectrum herbicide, may lead to soil and water pollution due to its persistence in the environment. Herein, the co-reduction method was employed to anchor bimetallic PdCu onto the Ni and nitrogen-doped 3D Flower-like Carbon Materials (Ni@NC), creating a composite material (PdCu/Ni@NC) with high specific surface area and good catalytic performance. This composite was used to modify screen-printed electrodes (SPE) to develop a portable and efficient Gly detection platform. In the presence of Cl⁻, the copper active sites convert to CuCl, achieving signal amplification. Upon the addition of Gly, a competitive reaction between Cu and Gly converts CuCl into a Cu-Gly complex, resulting in a sharp decrease in the electrochemical signal. This signal drop is used to detect Gly. The bimetallic PdCu nanoparticles (NPs) endowed the sensing platform with better stability and electrochemical performance due to their synergistic effect, and their stability was simply verified by Density functional theory (DFT). The sensor demonstrates a linear detection range spanning from 1 × 10⁻¹ ³ to 1 × 10⁻5 M, with a limit of detection (LOD) of 3.72 × 10⁻¹ 4 M. The sensor demonstrated a recovery rate of 95.9 % to 104.5 % in actual samples such as water and soil, indicating its potential for practical application.

A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta (POLE/POLD1) mutation.

Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

Mechanisms for carbon stock driving and scenario modeling in typical mountainous watersheds of northeastern China.

Watershed ecosystems play a pivotal role in maintaining the global carbon cycle and reducing global warming by serving as vital carbon reservoirs for sustainable ecosystem management. In this study, we based on the "quantity-mechanism-scenario" frameworks, integrate the MCE-CA-Markov and InVEST models to evaluate the spatiotemporal variations of carbon stocks in mid- to high-latitude alpine watersheds in China under historical and future climate scenarios. Additionally, the study employs the Geographic Detector model to explore the driving mechanisms influencing the carbon storage capacity of watershed ecosystems. The results showed that the carbon stock of the watershed increased by about 15.9 Tg from 1980 to 2020. Fractional Vegetation Cover (FVC), Digital Elevation Model (DEM), and Mean Annual Temperature (MAT) had the strongest explanatory power for carbon stocks. Under different climate scenarios, it was found that the SSP2-4.5 scenario had a significant rise in carbon stock from 2020 to 2050, roughly 24.1 Tg. This increase was primarily observed in the southeastern region of the watersheds, with forest and grassland effectively protected. Conversely, according to the SSP5-8.5 scenario, the carbon stock would decrease by about 50.53 Tg with the expansion of cultivated and construction land in the watershed's southwest part. Therefore, given the vulnerability of mid- to high-latitude mountain watersheds, global warming trends continue to pose a greater threat to carbon sequestration in watersheds. Our findings carry important implications for tackling potential ecological threats in mid- to high-latitude watersheds in the Northern Hemisphere and assisting policymakers in creating carbon sequestration plans, as well as for reducing climate change.

Impact of ultrasound-guided high-intensity focused ultrasound for the treatment of uterine fibroids on ovarian reserve and quality of life: a single-center prospective cohort study.

BACKGROUND: We aimed to evaluate changes in ovarian reserve and quality of life in women treated with ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids. METHODS: In this single-center prospective study, a total of 69 patients with uterine fibroids treated with USgHIFU from October 2018 to November 2021 were enrolled. Fibroid volume, anti-Müllerian hormone (AMH) levels, uterine fibroid symptom scores, and uterine fibroid symptoms and quality of life (UFS-QOL) questionnaire scores before and 1, 3, and 6 months after USgHIFU treatment were analyzed. Correlations between AMH levels and age, fibroid type, and fibroid location were assessed. RESULTS: Data from 54 of the 69 patients included in the present study were analyzed. The UFS-QOL scores at baseline and at 1 month and 6 months after USgHIFU treatment were 70 (50.75-87.50), 57 (44.75-80.00), and 52 (40.75-69.00) points, respectively (p < 0.001). The rate of fibroid volume reduction increased significantly at the 3-month follow-up compared with the 1-month follow-up (p < 0.001), and no significant change was observed between the 3-month and 6-month follow-ups (p > 0.99). The median AMH levels before and at 1, 3 and 6 months after treatment were 1.22 (0.16-3.28) ng/ml, 1.12 (0.18-2.52) ng/ml, 1.15 (0.19-2.08) ng/ml and 1.18 (0.36-2.43) ng/ml, respectively (p = 0.2). Multivariate linear regression analyses revealed that age was independently associated with AMH levels. CONCLUSIONS: USgHIFU treatment for uterine fibroids can significantly improve quality of life with minimal adverse effects on ovarian function.

DDX19A promotes gastric cancer cell proliferation and migration by activating the PI3K/AKT pathway.

BACKGROUND: DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role in gastric cancer remains unclear. The present study aimed to explore the role and underlying mechanism of DDX19A in the development of gastric cancer. METHODS: The expression of DDX19A in gastric cancer and paracancerous tissues was evaluated through quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The biological functions of DDX19A in gastric cancer were determined using CCK8, plate colony-forming, and Transwell migration assays. The specific mechanism of DDX19A in gastric cancer cells was studied using western blotting, RNA-binding protein immunoprecipitation, mRNA half-life detection, and nuclear and cytoplasmic RNA isolation. RESULTS: DDX19A was highly expressed in gastric cancer and positively associated with malignant clinicopathological features and poor prognosis. Additionally, DDX19A promoted gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition phenotypes. Mechanistically, DDX19A activated the PI3K/AKT pathway by upregulating phosphatidylinositol-3-kinase (PIK3CA) expression. Furthermore, DDX19A interacted with PIK3CA mRNA, stabilized it, and facilitated its export from the nucleus. CONCLUSIONS: Our study reveals a novel mechanism whereby DDX19A promotes the proliferation and migration of gastric cancer cells by enhancing the stability and nuclear export of PIK3CA mRNA, thereby activating the PI3K/AKT pathway.

Screening and identification of reactive metabolic compounds of Cortex Periplocae based on glutathione capture-mass spectrometry.

As a traditional Chinese medicine (TCM), Cortex Periplocae (CP) has a wide range of pharmacological effects, as well as toxic side effects. The main toxic components of it are cardiac glycosides, which tend to cause cardiotoxicity. Currently, it has also been reported in studies to cause hepatotoxicity, but it is not clear whether the hepatotoxicity is related to the toxicity caused by the reactive metabolites. This study aims to investigate the target components of CP that generate reactive metabolic toxicity. The fluorescent probe method was used to detect glutathione (GSH)-trapped reactive metabolites in a co-incubation system of CP extract with rat liver microsomes. Identification of GSH conjugates was performed by LC-MS/MS and that of the possible precursor components that produce reactive metabolites was conducted by UPLC-Q-TOF/MS. Cell viability assays were performed on HepG2 and L02 cells to determine the cytotoxicity of the target components. The findings of our study demonstrate that the extract derived from CP has the ability to generate metabolites that exhaust the intracellular GSH levels, resulting in the formation of GSH conjugates and subsequent cytotoxic effects. Through the utilization of the UPLC-Q-TOF/MS technique, we were able to accurately determine the molecular weight of the precursor compound in CP to be 355.1023. The primary evidence to determining the GSH conjugetes relies on the appearance of characteristic product ions resulting from central neutral loss (CNL) scanning of 129 Da and product scanning of m/z 660 in the positive MS/MS spectrum. Through analysis, it was ultimately ascertained that the presence of chlorogenic acid (CGA) and its isomers, namely neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA), could lead to the production of GSH conjugates, resulting in cytotoxicity at elevated levels. Taking these findings into consideration, the underlying cause for the potential hepatotoxicity of CP was initially determined.

Altered dynamic functional connectivity of nucleus accumbens subregions in major depressive disorder: the interactive effect of childhood trauma and diagnosis.

Major depressive disorder (MDD) with childhood trauma represents a heterogeneous clinical subtype of depression. Previous research has observed alterations in the reward circuitry centered around the nucleus accumbens (NAc) in MDD patients. However, limited investigations have focused on aberrant functional connectivity (FC) within NAc subregions among MDD with childhood trauma. Thus, this study adopts analyses of both static FC (sFC) and dynamic FC (dFC) to examine neurobiological changes in MDD with childhood trauma. The bilateral nucleus accumbens shell (NAc-shell) and nucleus accumbens core (NAc-core) were selected as the seeds. Four participant groups were included: MDD with childhood trauma (n = 48), MDD without childhood trauma (n = 30), healthy controls (HCs) with childhood trauma (n = 57), and HCs without childhood trauma (n = 46). Our findings revealed both abnormal sFC and dFC between NAc-shell and NAc-core and regions including the middle occipital gyrus (MOG), anterior cingulate cortex, and inferior frontal gyrus in MDD with childhood trauma. Furthermore, a significant correlation was identified between the dFC of the left NAc-shell and the right MOG in relation to childhood trauma. Additionally, abnormal dFC moderated the link between childhood abuse and depression severity. These outcomes shed light on the neurobiological underpinnings of MDD with childhood trauma.

Effects of different exercise regimens on prognosis of patients with chronic obstructive pulmonary disease: a systematic reviews and meta-analysis.

INTRODUCTION: Skeletal muscle dysfunction is a significant factor contributing to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Although exercise training is often recommended to enhance patient outcomes, there continues to be ongoing debate regarding its exact effects. OBJECTIVE: The aim of this study is to evaluate the effectiveness of endurance exercise, strength training and combined exercise on cardiorespiratory fitness (including maximal oxygen uptake, maximal minute ventilation, and the 6-minute walk test), strength of lower limbs (measured by leg press), and quality of life (using the COPD Assessment Test) in patients with COPD. By conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), our objective is to provide tailored training methods and intensity recommendations for patients with COPD in order to improve their quality of life. METHODS: The meta-analysis included 10 randomized controlled trials (RCTs) of exercise rehabilitation programs involving 180 patients with COPD that were retrieved from electronic databases (PubMed, Cochrane Library, and Embase). Two reviewers independently assessed the topical relevance, trial quality, and extracted data for the meta-analysis. RESULTS: Meta-analysis showed that primary outcomes representing exercise endurance were elevated under different exercise interventions compared to pre-test, such as maximal oxygen uptake (VO2max (ml/kg/min)) [SMD = 0.40, 95% CI (0.15, 0.64)] and the 6-min walk test (6MWT) [MD = 33.90, 95% CI (25.25, 42.55)], and primary outcomes representing strength also increased, such as leg press (1RM) [MD = 24.59, 95% CI (16.08, 33.11)], while secondary outcomes such as assessments of life such as the COPD Assessment Test (CAT) recovered [MD = 2.51, 95% CI (2.01, 3.00)], with all differences being statistically significant (p < 0.05). However, Maximum minute ventilation (VEmax (L)) [MD = 0.91, 95%CI (3.61, 5.43)] was not statistically significant (p > 0.05) when compared with the post-test data. The sensitivity test data were stable, and the results were reliable. We subgrouped the data from different types of exercise interventions and found that different types of exercise affected the experimental results. CONCLUSION: Exercise interventions have a positive effect on the treatment of patients with COPD, significantly improving functional capacity, aerobic capacity, and exercise tolerance, but they should be individualized and developed according to the patient's condition to achieve the best therapeutic effect.

SpSIZ1 from hyperaccumulator Sedum plumbizincicola orchestrates SpABI5 to fine-tune cadmium tolerance.

Sedum plumbizincicola is a renowned hyperaccumulator of cadmium (Cd), possesses significant potential for eco-friendly phytoremediation of soil contaminated with Cd. Nevertheless, comprehension of the mechanisms underpinning its Cd stress response remains constrained, primarily due to the absence of a comprehensive genome sequence and an established genetic transformation system. In this study, we successfully identified a novel protein that specifically responds to Cd stress through early comparative iTRAQ proteome and transcriptome analyses under Cd stress conditions. To further investigate its structure, we employed AlphaFold, a powerful tool for protein structure prediction, and found that this newly identified protein shares a similar structure with Arabidopsis AtSIZ1. Therefore, we named it Sedum plumbizincicola SIZ1 (SpSIZ1). Our study revealed that SpSIZ1 plays a crucial role in positively regulating Cd tolerance through its coordination with SpABI5. Overexpression of SpSIZ1 significantly enhanced plant resistance to Cd stress and reduced Cd accumulation. Expression pattern analysis revealed higher levels of SpSIZ1 expression in roots compared to stems and leaves, with up-regulation under Cd stress induction. Importantly, overexpressing SpSIZ1 resulted in lower Cd translocation factors (Tfs) but maintained relatively constant Cd levels in roots under Cd stress, leading to enhanced Cd stress resistance in plants. Protein interaction analysis revealed that SpSIZ1 interacts with SpABI5, and the expression of genes responsive to abscisic acid (ABA) through SpABI5-dependent signaling was significantly up-regulated in SpSIZ1-overexpressing plants with Cd stress treatment. Collectively, our results illustrate that SpSIZ1 interacts with SpABI5, enhancing the expression of ABA downstream stress-related genes through SpABI5, thereby increasing Cd tolerance in plants.

The mutation of CsSUN, an IQD family protein, is responsible for the short and fat fruit (sff) in cucumber (Cucumis sativus L.).

The fruit shape of cucumber is an important agronomic trait, and mining regulatory genes, especially dominant ones, is vital for cucumber breeding. In this study, we identified a short and fat fruit mutant, named sff, from an EMS mutagenized population. Compared to the CCMC (WT), sff (MT) exhibited reduced fruit length and increased dimeter. Segregation analysis revealed that the sff phenotype is controlled by a semi-dominant single gene with dosage effects. Through map-based cloning, the SFF locus was narrowed down to a 52.6 kb interval with two SNPs (G651A and C1072T) in the second and third exons of CsaV3_1G039870, which encodes an IQD family protein, CsSUN. The G651A within the IQ domain of CsSUN was identified as the unique SNP among 114 cucumber accessions, and it was the primary cause of the functional alteration in CsSUN. By generating CsSUN knockout lines in cucumber, we confirmed that CsSUN was responsible for sff mutant phenotype. The CsSUN is localized to the plasma membrane. CsSUN exhibited the highest expression in the fruit with lower expression in sff compared to WT. Histological observations suggest that the sff mutant phenotype is due to increased transverse cell division and inhibited longitudinal cell division. Transcriptome analysis revealed that CsSUN significantly affected the expression of genes related to cell division, expansion, and auxin signal transduction. This study unveils CsSUN's crucial role in shaping cucumber fruit and offers novel insights for cucumber breeding.

Sleep disturbance in rodent models and its sex-specific implications.

Sleep disturbances, encompassing altered sleep physiology or disorders like insomnia and sleep apnea, profoundly impact physiological functions and elevate disease risk. Despite extensive research, the underlying mechanisms and sex-specific differences in sleep disorders remain elusive. While polysomnography serves as a cornerstone for human sleep studies, animal models provide invaluable insights into sleep mechanisms. However, the availability of animal models of sleep disorders is limited, with each model often representing a specific sleep issue or mechanism. Therefore, selecting appropriate animal models for sleep research is critical. Given the significant sex differences in sleep patterns and disorders, incorporating both male and female subjects in studies is essential for uncovering sex-specific mechanisms with clinical relevance. This review provides a comprehensive overview of various rodent models of sleep disturbance, including sleep deprivation, sleep fragmentation, and circadian rhythm dysfunction. We evaluate the advantages and disadvantages of each model and discuss sex differences in sleep and sleep disorders, along with potential mechanisms. We aim to advance our understanding of sleep disorders and facilitate sex-specific interventions.