Dynamic changes in lysosome-related pathways in APP/PS1 mice with aging.

Senile plaque, composed of amyloid ß protein (Aß) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aß aggregates exert age-dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age-gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of ß-amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age-dependent Aß deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age-dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age-dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age-gradient changes in the autophagy-lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

Comprehensive bioremediation effect of phosphorus-mineralized bacterium Enterobacter sp. PMB-5 on cadmium contaminated soil-crop system.

Phosphate-mineralizing bacteria (PMBs) have been widely studied by inducing phosphate heavy metal precipitation, but current researches neglect to study their effects on soil-microbe-crop systems on cadmium (Cd) contaminated. Based on this, a strain PMB, Enterobacter sp. PMB-5, was inoculated into Cd contaminated pots to detect soil characteristics, Cd occurrence forms, soil biological activities, plant physiological and biochemical indicators. The results showed that the inoculation of strain PMB-5 significantly increased the available phosphorus content (85.97%-138.64%), Cd-residual fraction (11.04%-29.73%), soil enzyme activities (31.94%-304.63%), plant biomass (6.10%-59.81%), while decreased the state of Cd-HOAc (11.50%-31.17%) and plant bioconcentration factor (23.76%-44.24%). These findings indicated that strain PMB-5 could perform the function of phosphorus solubilization to realize the immobilization of Cd in the complex soil environment. Moreover, SEM-EDS, FTIR, XPS, and XRD analysis revealed that strain PMB-5 does not significantly alter the soil morphology, structure, elemental distribution, and chemical composition, which suggested that remediation of Cd contamination using strain PMB-5 would not further burden the soil. This research implies that PMB-5 could be a safe and effective bioinoculant for remediating Cd-contaminated soils, contributing to the sustainable management of soil health in contaminated environments.

The 'whole landscape' of research on systemic sclerosis over the past 73 years.

OBJECTIVE: This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry. METHODS: Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots. RESULTS: From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020-2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations. CONCLUSION: In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.

Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer.

BACKGROUND: Colorectal cancer is a common malignant tumor in China, and its incidence in the elderly is increasing annually. Inflammatory bowel disease is a group of chronic non-specific intestinal inflammatory diseases, including ulcerative colitis and Crohn's disease. AIM: To assess the effect of screening colonoscopy frequency on colorectal cancer mortality. METHODS: We included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December 2022. Surgical indicators, oncological indicators, and survival rates were compared between the groups. The results of 104 patients who met the above criteria were extracted from the database (laparoscopic colectomy group = 63, open colectomy group = 41), and there were no statistically significant differences in the baseline data or follow-up time between the two groups. RESULTS: Intraoperative blood loss, time to first ambulation, and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy group. The differences in overall mortality, tumor-related mortality, and recurrence rates between the two groups were not statistically significant, and survival analysis showed that the differences in the cumulative overall survival, tumor-related survival, and cumulative recurrence-free rates between the two groups were not statistically significant. CONCLUSION: In elderly patients with colorectal cancer, laparoscopic colectomy has better short-term outcomes than open colectomy, and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

Differential Expression of KIF18B in Gastric Cancer and Its Role in Chemotherapy Sensitivity.

Gastric cancer (GC) is a main cause of cancer death in the world, and improving the chemotherapy sensitivity can enhance the chemotherapy efficacy of GC. The study objective is to explore the differential KIF18B expression in GC and its effect on GC chemotherapy sensitivity. The KIF18B expression in GC tissues and adjacent normal tissues was analyzed by real-time quantitative polymerase chain reaction. The relationship between differential KIF18B expression and different clinicopathological features was detected. It was found that KIF18B was highly expressed in GC tissues, and KIF18B expression was differential in patients with different clinicopathological features. The upregulation of KIF18B has a positive correlation with the poor therapeutic effect and high KIF18 was associated with lower 3-year overall survival and disease-free survival. The KIF18B-downregulated NCI-N87 cells were constructed and tested by cell counting kit-8 assay and colony formation. Cell migration and invasion were detected by Transwell assay. The xenograft tumor model was established to observe the effect of KIF18B on the efficacy of chemotherapy. The upregulation of KIF18B reduced the chemotherapy sensitivity of GC cells and enhanced their proliferation, migration, and invasion. Silencing KIF18B inhibited tumor growth and promoted chemotherapy efficacy in vivo. In summary, KIF18B inhibitor may have a potential function for improving the efficacy of chemotherapy in GC.

Tree shrews as a new animal model for systemic sclerosis research.

Objective: Systemic sclerosis (SSc) is a chronic systemic disease characterized by immune dysregulation and fibrosis for which there is no effective treatment. Animal models are crucial for advancing SSc research. Tree shrews are genetically, anatomically, and immunologically closer to humans than rodents. Thus, the tree shrew model provides a unique opportunity for translational research in SSc. Methods: In this study, a SSc tree shrew model was constructed by subcutaneous injection of different doses of bleomycin (BLM) for 21 days. We assessed the degree of inflammation and fibrosis in the skin and internal organs, and antibodies in serum. Furthermore, RNA sequencing and a series of bioinformatics analyses were performed to analyze the transcriptome changes, hub genes and immune infiltration in the skin tissues of BLM induced SSc tree shrew models. Multiple sequence alignment was utilized to analyze the conservation of selected target genes across multiple species. Results: Subcutaneous injection of BLM successfully induced a SSc model in tree shrew. This model exhibited inflammation and fibrosis in skin and lung, and some developed esophageal fibrosis and secrum autoantibodies including antinuclear antibodies and anti-scleroderma-70 antibody. Using RNA sequencing, we compiled skin transcriptome profiles in SSc tree shrew models. 90 differentially expressed genes (DEGs) were identified, which were mainly enriched in the PPAR signaling pathway, tyrosine metabolic pathway, p53 signaling pathway, ECM receptor interaction and glutathione metabolism, all of which are closely associated with SSc. Immune infiltration analysis identified 20 different types of immune cells infiltrating the skin of the BLM-induced SSc tree shrew models and correlations between those immune cells. By constructing a protein-protein interaction (PPI) network, we identified 10 hub genes that were significantly highly expressed in the skin of the SSc models compared to controls. Furthermore, these genes were confirmed to be highly conserved in tree shrews, humans and mice. Conclusion: This study for the first time comfirmed that tree shrew model of SSc can be used as a novel and promising experimental animal model to study the pathogenesis and translational research in SSc.

Strong, tough and anisotropic bioinspired hydrogels.

Soft materials are widely used in tissue engineering, soft robots, wearable electronics, etc. However, it remains a challenge to fabricate soft materials, such as hydrogels, with both high strength and toughness that are comparable to biological tissues. Inspired by the anisotropic structure of biological tissues, a novel solvent-exchange-assisted wet-stretching strategy is proposed to prepare anisotropic polyvinyl alcohol (PVA) hydrogels by tuning the macromolecular chain movement and optimizing the polymer network. The reinforcing and toughening mechanisms are found to be "macromolecule crystallization and nanofibril formation". These hydrogels exhibit excellent mechanical properties, such as extremely high fracture stress (12.8 ± 0.7 MPa) and fracture strain (1719 ± 77%), excellent modulus (4.51 ± 0.76 MPa), high work of fracture (134.47 ± 9.29 MJ m-3), and fracture toughness (305.04 kJ m-2) compared with other strong hydrogels and even natural tendons. In addition, excellent conductivity, strain sensing capability, water retention, freezing resistance, swelling resistance, and biocompatibility can also be achieved. This work provides a new and effective method to fabricate multifunctional anisotropic hydrogels with high tunable strength and toughness with potential applications in the fields of regenerative medicine, flexible sensors, and soft robotics.

Loco-regional radiotherapy in de novo metastatic nasopharyngeal carcinoma with chemotherapy and immunotherapy: A real-world retrospective study from two cancer centers.

BACKGROUND: Immunochemotherapy has become the first-line treatment for initial diagnosed metastatic nasopharyngeal carcinoma (mNPC). Loco-regional radiotherapy combined with systemic chemotherapy significantly improves the survival. However, the safety and efficacy of loco-regional radiotherapy combined with immunochemotherapy remained unknown. METHODS: Patients with de novo mNPC who received immunochemotherapy followed by loco-regional radiotherapy were included from two cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. RESULTS: From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median follow-up was 28 months (range 14-47 months). No one died. One-year, 2-year, and 3-year PFS rate was 93.8%, 58.4% and 50.1%, respectively. Radiotherapy-related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%). CONCLUSIONS: Loco-regional radiotherapy provided a promising efficacy with modest toxicity for patients with mNPC who received immunochemotherapy.

TIM22 and TIM29 inhibit HBV replication by up-regulating SRSF1 expression.

Hepatitis B virus (HBV) infection is a serious global health problem. After the viruses infect the human body, the host can respond to the virus infection by coordinating various cellular responses, in which mitochondria play an important role. Evidence has shown that mitochondrial proteins are involved in host antiviral responses. In this study, we found that the overexpression of TIM22 and TIM29, the members of the inner membrane translocase TIM22 complex, significantly reduced the level of intracellular HBV DNA and RNA and secreted HBV surface antigens and E antigen. The effects of TIM22 and TIM29 on HBV replication and transcription is attributed to the reduction of core promoter activity mediated by the increased expression of SRSF1 which acts as a suppressor of HBV replication. This study provides new evidence for the critical role of mitochondria in the resistance of HBV infection and new targets for the development of treatment against HBV infection.

Exploring the potential mechanism of Heng-Gu-Gu-Shang-Yu-He-Ji therapy for osteoporosis based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Heng-Gu-Gu-Shang-Yu-He-Ji (Osteoking, OK) is a well-known formula for fracture therapy. In clinic, OK is effective in treating fractures while alleviating osteoporosis (OP) symptoms. However, active components of OK and the associated molecular mechanisms remain not fully elucidated. AIM OF THE STUDY: This study aims to systematically evaluate the anti-osteoporosis efficacy of OK and for the first time combine network pharmacology with high-throughput whole gene transcriptome sequencing to study its underlying mechanism. MATERIALS AND METHODS: In this study, the osteoporosis model was established by the castration of both ovaries. The level of serum bone turnover factor was detected by enzyme-linked immunosorbent assay. Micro-CT and HE staining were used to observe the changes of bone histopathology, and nano-indentation technique was used to detect the biomechanical properties of rat bone. The main active Chemical components of OK were identified using UPLC-DAD. Efficacy verification and mechanism exploration were conducted by network pharmacology, molecular docking, whole gene transcriptomics and in vivo experiments. RESULTS: In our study, OK significantly improved bone microarchitecture and bone biomechanical parameters in OVX rats, reduced osteoclast indexes such as C-telopeptide of type I collage (CTX-I) and increased Osteoprotegerin (OPG)/Receptor activator of NF-κB ligand (RANKL) levels. Mechanistically, PI3K/AKT pathway was a common pathway for genome enrichment analysis (KEGG) of both network pharmacology and RNA-seq studies. G protein-ß-like protein (GßL), Ribosomal-protein S6 kinase homolog 2 (S6K2), and Phosphoinositide 3-kinase (PI3K) appeared differentially expression in the PI3K-AKT signaling pathway. These results were also confirmed by qRT-PCR and immunohistochemistry. CONCLUSIONS: OK may be used to treat osteoporosis, at least partly by activating PI3K/AKT/mTORC1 signaling pathway.

Comparative study of female pelvic floor among undeformed high-resolution thin-sectional anatomical (visible human) images and MRI and ultrasound images.

PURPOSE: Using visible human, MRI and ultrasound images, we aim to provide an anatomical basis for the identification and diagnosis of pelvic floor structure and disease by ultrasound imaging. METHODS: One Chinese visible human (CVH) image, one American visible human image, 9 MRI images of normal volunteers, and 40 ultrasound images of normal volunteers or pelvic organ prolapse patients were used. Pelvic organs, pelvic floor muscles, and the connective tissue in CVH, VHP, MRI, and ultrasound images were selected for comparative study. RESULTS: We successfully identified the boundary of the anal sphincter complex, including the subcutaneous, superficial, and deep parts of the external anal sphincter, conjoined longitudinal muscles and internal anal sphincter; the levator ani muscle (LAM), including the internal and external parts of the pubovisceral muscle and the superficial and deep parts of the puborectal muscle; the urethral sphincter complex, including the urethral sphincter proper and the urethral compressor; and the perineal body, the rectoperineal muscle and superficial transverse perineal muscle. CONCLUSIONS: We successfully recognized and studied the location, subdivisions, 2D morphology and spatial relationships of the LAM, anal sphincter complex, urethral sphincter complex and perineal body in ultrasound images, thereby helping sonologists or clinicians accurately identify pelvic floor muscles and supporting structures in ultrasound images.

Gypenoside IX restores Akt/GSK-3ß pathway and alleviates Alzheimer's disease-like neuropathology and cognitive deficits.

The main pathological changes of Alzheimer's disease (AD), a progressive neurodegenerative disorder, include senile plaque (deposited by amyloid beta), neurofibrillary tangle (formed by paired helical filaments composed of hyperphosphorylated tau), and massive loss of neurons. Currently there is a lack of ideal drugs to halt AD progression. Gypenosides (GPs), a kind of natural product, possesses potential therapeutic effects for neurodegenerative diseases, including AD. However, the specific role and mechanism of GPs for AD remain unclear. In the current study, we used staurosporine (STP), an inducer of apoptosis and causing tau hyperphosphorylation, to mimic AD models, and explored the role and mechanism of Gypenoside IX (one of the extracts of Gynostemma, GP for short name in our experiments) in STP treated primary hippocampal neurons and rats. We found STP not only increased apoptosis and tau hyperphosphorylation, but also significantly increased Aß production, resulting in synaptic dysfunction and cognitive decline in mimic AD models by STP. GP was found to rescue apoptosis and cognitive impairments caused by STP treatment. Moreover, GP recovered the decreased synaptic proteins PSD95, Synaptophysin and GluR2, and blocked dendritic spine loss. Interestingly, GP decreased the STP induced tau hyperphosphorylation at different sites including S-199, S-202, T-205, T-231, S-262, S-396, and S-404, and at the same time decreased Aß production through down-regulation of BACE1 and PS1. These effects in STP treated primary hippocampal neurons and rats were accompanied with a restoration of AKT/GSK-3ß signaling axis with GP treatment, supporting that dysregulation of AKT/GSK-3ß pathway might be involved in STP related AD pathogenesis. The results from our research proved that GP might be a potential candidate compound to reduce neuronal damage and prevent the cognitive decline in AD.

The mediating role of sleep quality in the relationship between social support and depressive symptoms in early pregnant women.

OBJECTIVE: To explore the mediating effect of sleep quality between social support and depressive symptoms in pregnant woman at the early pregnancy stage. METHODS: Pittsburgh sleep quality index (PSQI), social support revalued scale (SSRS), and self-rating depression scale (SDS) were used to investigate the sleep quality, social support status and depression of 269 pregnant women in early pregnancy in Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from July 2022 to December 2022. Pearson correlation analyses and Bootstrap were used to test the correlation and mediating effect between variables. RESULTS: The social support scores of pregnant women were inversely proportional to the scores of sleep quality and depression (r = -0.178 and -0.219, P < 0.05). The sleep quality of pregnant woman score was positively correlated with depression symptom score (r = 0.139, P < 0.05). The sleep quality of pregnant women in early pregnancy played a partial mediating role between social support and depressive symptoms, and the mediating effect value was -0.029 (95% CI: -0.057--0.007). CONCLUSION: Social support can affect the occurrence of depression in pregnant woman at the early pregnancy stage, and sleep quality plays a partial mediating role.

SRY-box transcription factor 21 antisense divergent transcript 1: Regulatory roles and clinical significance in neoplastic conditions and Alzheimer's Disease.

SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) is a multifaceted long non-coding RNA (lncRNA) that plays diverse roles in both neoplastic conditions and Alzheimer's disease. Its aberrant expression intricately regulates a wide spectrum of cellular processes, spanning from epithelial-mesenchymal transition (EMT), apoptosis, migration, metastasis, and stemness to drug resistance. SOX21-AS1 achieves these effects through its involvement in the competitive endogenous RNA (ceRNA) network, modulation of downstream genes, and regulation of critical pathways, including PI3K/AKT, Hippo, Wnt/ß-catenin, and ERK signaling. Of significant clinical relevance, SOX21-AS1 expression has shown robust correlations with various clinical-pathological features. Moreover, it has demonstrated promising prognostic and diagnostic potential across a spectrum of tumors, as evidenced by existing literature and TCGA pan-cancer analyses. In Alzheimer's disease, SOX21-AS1 assumes a distinctive role. It influences neuronal viability, apoptosis, and oxidative stress by interacting with miR-107 and miR-132, and affecting the PI3K/AKT and Wnt signaling pathways. This comprehensive review sheds light on the functions of SOX21-AS1 and the regulated mechanisms underpinning its impact on neoplastic conditions and Alzheimer's disease. It underscores the clinical significance of SOX21-AS1 and positions it as a promising therapeutic target in both the oncological and neurodegenerative domains.

Biological control of Magnaporthe oryzae using natively isolated Bacillus subtilis G5 from Oryza officinalis roots.

Rice blast, caused by Magnaporthe oryzae, is a major threat to global rice production causing significant crop losses and impacting grain quality. The annual loss of rice production due to this disease ranges from 10% to 30%. The use of biologically controlled strains, instead of chemical pesticides, to control plant diseases has become a research hotspot. In this study, an antagonistic endophytic bacterial strain was isolated from the roots of Oryza officinalis using the traditional isolation and culture methods. A phylogenetic tree based on 16S RNA and whole-genome sequencing identified isolate G5 as a strain of Bacillus subtilis. This isolate displayed strong antagonistic effects against different physiological strains of M. oryzae. After co-culture in LB medium for 7 days, the inhibition rates of the mycelial growth of four strains of M. oryzae, ZB15, WH97, Guy11, and T-39800E were 98.07 ± 0.0034%, 98.59 ± 0.0051%, 99.16 ± 0.0012%, and 98.69 ± 0.0065%, respectively. Isolate G5 significantly inhibited the formation of conidia of M. oryzae, with an inhibition rate of 97% at an OD600 of 2. Isolate G5 was able to provide 66.81% protection against rice blast under potted conditions. Whole-genome sequencing revealed that the genome size of isolate G5 was 4,065,878 bp, including 4,182 coding genes. Using the anti-SMASH software, 14 secondary metabolite synthesis gene clusters were predicted to encode antifungal substances, such as fengycin, surfactin, and bacilysin. The G5 isolate also contained genes related to plant growth promotion. These findings provide a theoretical basis for expounding the biocontrol mechanisms of this strain and suggest further development of biogenic agents that could effectively inhibit rice blast pathogen growth and reduce crop damage, while being environmentally friendly, conducive to ecological development, and a sustainable alternative to chemical pesticides. This study also enriches the relevant research on endophytes of wild rice, which proves that wild rice is a valuable microbial resource bank.

Cobalt-based conjugated coordination polymers with tunable dimensions for electrochemical sensing of p-nitrophenol.

Using planar π-conjugated 2,5-diamino-1,4-benzenedithiol as organic ligand, Co-based conjugated coordination polymers (CoCCPs) with different morphology were prepared through controlling the injection rate of Co2+. When the injection rate decreases from 1.00 to 0.25 mL min-1, the obtained CoCCPs change from 2D nanosheets to quasi-1D nanorods. It is found that the different-shaped CoCCPs exhibit varying electrochemical sensing performance. The prepared CoCCPs-1 with quasi-1D nanowires and porous network structure possesses larger active area, faster electron transfer and higher accumulation ability. Moreover, the CoCCPs-1 is more active for the oxidation of p-nitrophenol (PNP), and greatly enhances its oxidation signal. Based on the morphology-tuned sensing performance of CoCCPs, a highly-sensitive electrochemical sensor has been developed for PNP, with detection limit of 0.00986 µM (9.86 nM). It was used in the analysis of wastewater samples, and the results is validated by other instrumental method.

Efficacy and safety of different Janus kinase inhibitors combined with methotrexate for the treatment of rheumatoid arthritis: a single-center randomized trial.

OBJECTIVE: To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. METHODS: This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. RESULTS: Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. CONCLUSION: The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

Exosomes from adipose-derived mesenchymal stem cells improve liver fibrosis by regulating the miR-20a-5p/TGFBR2 axis to affect the p38 MAPK/NF-κB pathway.

OBJECTIVE: Human adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) are active constituents for treating liver fibrosis. This paper attempted to preliminarily explain the functional mechanism of ADSC-Exos in liver fibrosis through the p38 MAPK/NF-κB pathway. METHODS: The cell models of hepatic fibrosis were established by inducing LX-2 cells with TGF-ß1. Mouse models of liver fibrosis were established by treating mice with CCl4. The in vivo and in vitro models of liver fibrosis were treated with ADSC-Exos. ADSCs were identified by flow cytometry/Alizarin red/oil red O/alcian blue staining. ADSC-Exos were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. LX-2 cell proliferation/viability were evaluated by MTT/BrdU assays. Exosomes were tracked in vivo and body weight changes in mice were monitored. Hepatic pathological changes were observed by HE/Masson staining. α-SMA/collagen I levels in liver tissues were assessed by immunohistochemistry. HA/PIIINP concentrations were measured using the magnetic particle chemiluminescence method. Liver function was assessed using an automatic analyzer. miR-20a-5p level was measured by RT-qPCR. The mRNA levels of fibrosis markers were determined by RT-qPCR, and their protein levels and levels of MAPK/NF-κB pathway-related proteins, as well as TGFBR2 protein level were measured by Western blot. The P65 nuclear expression in mouse liver tissues was quantified by immunofluorescence. RESULTS: ADSC-Exos suppressed TGF-ß1-induced LX-2 cell proliferation and fibrosis and reduced mRNA and protein levels of fibrosis markers in vitro. ADSC-Exos ameliorated liver fibrosis by inhibiting the p38 MAPK/NF-κB pathway activation. ADSC-Exos inhibited activation of the p38 MAPK/NF-κB pathway via regulating the miR-20a-5p/TGFBR2 axis. The in vivo experiment asserted that ADSC-Exos were mainly distributed in the liver, and ADSC-Exos relieved liver fibrosis in mice, which was evidenced by alleviating decreased body weight, reducing collagen and enhancing liver function, and repressed the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis. CONCLUSION: ADSC-Exos attenuated liver fibrosis by suppressing the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis.

Identification of histone deacetylase inhibitors as neutrophil recruitment modulators in zebrafish using a chemical library screen.

Tissue injury-induced neutrophil recruitment is a prerequisite for the initiation and amplification of inflammatory responses. Although multiple proteases and enzymes involved in post-translational modification (PTM) of proteins regulate leukocyte recruitment, an unbiased functional screen of enzymes regulating inflammatory leukocyte recruitment has yet to be undertaken. Here, using a zebrafish tail fin amputation (TFA) model to screen a chemical library consisting of 295 compounds that target proteases and PTM enzymes, we identified multiple histone deacetylase (HDAC) inhibitors that modulate inflammatory neutrophil recruitment. AR-42, a pan-HDAC inhibitor, was shown to inhibit neutrophil recruitment in three different zebrafish sterile tissue injury models: a TFA model, a copper-induced neuromast damage and mechanical otic vesicle injury (MOVI) model, and a sterile murine peritonitis model. RNA sequencing analysis of AR-42-treated fish embryos revealed downregulation of neutrophil-associated cytokines/chemokines, and exogenous supplementation with recombinant human IL-1ß and CXCL8 partially restored the defective neutrophil recruitment in AR-42-treated MOVI model fish embryos. We thus demonstrate that AR-42 non-cell-autonomously modulates neutrophil recruitment by suppressing transcriptional expression of cytokines/chemokines, thereby identifying AR-42 as a promising anti-inflammatory drug for treating sterile tissue injury-associated diseases.