The time sensitive and dose-responsive association between parental corporal punishment and sleep disturbances in preschoolers: A prospective cohort study.

BACKGROUND: To examine whether parental corporal punishment is associated with increased risk of concurrent and later sleep disturbances among preschoolers, and whether the association is time-sensitive or dose-responsive. METHODS: This 3-year prospective cohort study used data from the Shanghai Children's Health, Education and Lifestyle Evaluation, Preschool(SCHEDULE-P). Participants were newly enrolled preschoolers in November 2016(wave 1) and followed up in April 2018(wave 2) and April 2019(wave 3). Parents reported the children's corporal punishment experiences and sleep disturbances at each wave survey. Children's risk of sleep disturbances in relation to corporal punishment was examined using logistic regression, adjusting for children's age, gender, emotional/behavioral problems, family annual income, and maternal educational level. RESULTS: The participants of 19,668 children included 9436(47.98 %) females, with a mean age of 3.73(SD = 0.29) years at wave 1. Exposure to corporal punishment was associated with increased odds of concurrent sleep disturbances at wave 1, 2, and 3 (aOR,1.57; 95 % CI, 1.40-1.75; P < .001; aOR,1.60; 95 % CI, 1.43-1.80; P < .001; aOR,1.74; 95 % CI, 1.54-1.95; P < .001), respectively. Exposure to corporal punishment at any wave of preschool was associated with increased odds of sleep disturbances at wave 3, and the risks were greater for proximal and accumulative corporal punishment exposure. CONCLUSION: There is a time-sensitive and dose-responsive association between corporal punishment and sleep disturbance among preschoolers, with greater risk of sleep disturbances for proximal and accumulative exposure of corporal punishment. Promoting positive parenting strategies and avoiding corporal punishment can be a promising strategy to prevent and intervene sleep disturbances in preschoolers.

The genomes of Dahlia pinnata, Cosmos bipinnatus, and Bidens alba in tribe Coreopsideae provide insights into polyploid evolution and inulin biosynthesis.

BACKGROUND: The Coreopsideae tribe, a subset of the Asteraceae family, encompasses economically vital genera like Dahlia, Cosmos, and Bidens, which are widely employed in medicine, horticulture, ecology, and food applications. Nevertheless, the lack of reference genomes hinders evolutionary and biological investigations in this tribe. RESULTS: Here, we present 3 haplotype-resolved chromosome-level reference genomes of the tribe Coreopsideae, including 2 popular flowering plants (Dahlia pinnata and Cosmos bipinnatus) and 1 invasive weed plant (Bidens alba), with assembled genome sizes 3.93 G, 1.02 G, and 1.87 G, respectively. We found that Gypsy transposable elements contribute mostly to the larger genome size of D. pinnata, and multiple chromosome rearrangements have occurred in tribe Coreopsideae. Besides the shared whole-genome duplication (WGD-2) in the Heliantheae alliance, our analyses showed that D. pinnata and B. alba each underwent an independent recent WGD-3 event: in D. pinnata, it is more likely to be a self-WGD, while in B. alba, it is from the hybridization of 2 ancestor species. Further, we identified key genes in the inulin metabolic pathway and found that the pseudogenization of 1-FEH1 and 1-FEH2 genes in D. pinnata and the deletion of 3 key residues of 1-FFT proteins in C. bipinnatus and B. alba may probably explain why D. pinnata produces much more inulin than the other 2 plants. CONCLUSIONS: Collectively, the genomic resources for the Coreopsideae tribe will promote phylogenomics in Asteraceae plants, facilitate ornamental molecular breeding improvements and inulin production, and help prevent invasive weeds.

Photoinduced decarboxylative germylation of α-fluoroacrylic acids: access to germylated monofluoroalkenes.

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

Enhanced stiffness in peri-cancerous tissue: a marker of poor prognosis in papillary thyroid carcinoma with lymph node metastasis.

BACKGROUND: The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Notably, there is evidence suggesting an association between tissue stiffness and the aggressiveness of the disease. We therefore aimed to explore the effect of tissue stiffness on LNM-related invasiveness in PTC patients. METHOD: A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on their pathological results. The effects of interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell) on the LNM-related recurrence rate and mortality in each patient with PTC subgroup were analyzed. The activation of cancer-associated fibroblasts (CAFs) and extracellular matrix component type 1 collagen (COL-I) in the lesion were compared and analyzed across different subgroups. The underlying biological basis of differences in each subgroup was identified using RNA sequencing (RNA-seq) data. RESULTS: The Eshell value and Eshell/E in the LNM group were significantly higher than those in the non-LNM group of patients with PTC (Eshell: 72.72 ±â€…5.63 vs 66.05 ±â€…4.46; Eshell/E: 1.20 ±â€…1.72 vs 1.09 ±â€…1.10, P < .001). When Eshell/E > 1.412 and LNM were both present, the recurrence rate and mortality were significantly increased compared to those of group of patients with LNM (91.67% and 7.29%, respectively). The CAF activation and COL-I content in the Eshell/E+ group were significantly higher than those in the Eshell/E- group (all P < .001), and the RNA-seq results revealed significant extracellular matrix (ECM) remodeling in the LNM-Eshell/E+ group. CONCLUSIONS: Stiff peri-cancerous tissue induced CAF activation, COL-I deposition, and ECM remodeling, resulting in a poor prognosis for PTC patients with LNM.

CACIMAR: cross-species analysis of cell identities, markers, regulations, and interactions using single-cell RNA sequencing data.

Transcriptomic analysis across species is increasingly used to reveal conserved gene regulations which implicate crucial regulators. Cross-species analysis of single-cell RNA sequencing (scRNA-seq) data provides new opportunities to identify the cellular and molecular conservations, especially for cell types and cell type-specific gene regulations. However, few methods have been developed to analyze cross-species scRNA-seq data to uncover both molecular and cellular conservations. Here, we built a tool called CACIMAR, which can perform cross-species analysis of cell identities, markers, regulations, and interactions using scRNA-seq profiles. Based on the weighted sum models of the conserved features, we developed different conservation scores to measure the conservation of cell types, regulatory networks, and intercellular interactions. Using publicly available scRNA-seq data on retinal regeneration in mice, zebrafish, and chick, we demonstrated four main functions of CACIMAR. First, CACIMAR allows to identify conserved cell types even in evolutionarily distant species. Second, the tool facilitates the identification of evolutionarily conserved or species-specific marker genes. Third, CACIMAR enables the identification of conserved intracellular regulations, including cell type-specific regulatory subnetworks and regulators. Lastly, CACIMAR provides a unique feature for identifying conserved intercellular interactions. Overall, CACIMAR facilitates the identification of evolutionarily conserved cell types, marker genes, intracellular regulations, and intercellular interactions, providing insights into the cellular and molecular mechanisms of species evolution.

The Effect of Human Umbilical Cord Mesenchymal Stem Cell on Premature Ovarian Cell Senilism Through miR-10a.

Objective: To investigate the potential protective impact of miR-10a-modified HUMSCs-derived exosomes on both premature ovarian failure and the functionality of ovarian granulosa cells in a POF model. Methods: KGN cells were co-cultured with cisplatin-diaminedichloroplatinum (II) (10 µM) for 24 h to establish an in vitro POF model. The cells were distributed into three distinct groups: the control group, the POF group, and the POF + HUCMSC group. The plasmid sh-NC, sh-miR-10 a and miR-10 a mimic were transfected into KGN cells. After co-cultured with HUCMSC-EVs for 48 h, they were divided into HUCMSC group, sh-miR-10 a-HUMSCs-exosomes group and miR-10 a-HUMSCs-exosomes group. Flow cytometry was adopted to assess the impact of HUMSCs surface immune antigens and miR-10a-HUCMSCs-exosomes on KGN cell apoptosis. Additionally, the evaluation of cell proliferation was carried out through CCK-8 and EDU assays. Western blot analysis was utilized to detect the Caspase-3, Bax, and Bcl-2 proteins levels. Furthermore, the levels of TNF-α, IL-6, IL-10, MDA, SOD, and CAT were quantified using ELISA. Results: Compared with the Control group, the POF group inhibited the growth of ovarian granulosa cells (P<0.01), reduced the number of EDU cells (P<0.01), and increased the protein expression of Caspase-3 (P<0.05) and Bax (P<0.01). HUMSCs treatment significantly down-regulated the expression of IL-6, TNF-α and MDA, while up-regulating the expression of IL-10, SOD and CAT (P<0.01); the overexpression of miR-10a promoted cell growth, besides, the introduction of miR-10a-HUMSCs-derived exosomes led to an elevation in the proliferation rate of OGCs affected by POF and concurrently suppressed the apoptosis rate. Conclusion: HUMSCs-derived exosomes modified by miR-10a have protective effects on premature ovarian failure and ovarian granulosa cell function in POF model.

Knowledge mapping of disease-modifying therapy (DMT) in multiple sclerosis (MS): A bibliometrics analysis.

Background: Multiple sclerosis (MS) is a heterogeneous autoimmune disease, with a rapidly evolving body of literature on disease-modifying therapy (DMT) that urgently needs to be synthesized and regularized. Methods: The original material used for the analysis was obtained from the Web of Science Core Collection (WoSCC) in the Science Citation Index Expanded Edition (SCI-E). The data material was accessed through VOSviewer, Citespace, R package "Bibliometrix", and Scimago Graphica for data analysis and visualization. Among them, the clustering algorithm based on the Largest Likelihood Ratio (LLR) and the burst citation algorithm is the key. Results: As of November 6th, 2022, 4142 publications related to emerging disease-modifying therapies (e-DMT) for MS, 6521 publications related to traditional disease-modifying therapies (t-DMT) for MS, and 1793 publications in cross-cutting disease-modifying therapies (I-DMT) for MS were included in the analysis, respectively. Publications related to DMT in MS were analyzed descriptively (for three subjects: country, institution, and author) and predictively (for two subjects: keywords and references) separately according to three sections: e-DMT, t-DMT, and I-DMT. Topics that still have relevant reference output as of 2022 include the safety of Coronavirus disease 2019 (COVID-19) mRNA vaccination, therapeutic inertia (TI), cladribine tablets, autologous hematopoietic stem cell transplantation (aHSCT), progressive multiple sclerosis, and pediatric multiple sclerosis. Conclusion: The future research focus for MS DMT is the combination trial or cross-trial of various treatment methods to improve the development of individualized treatment plans for MS patients. The exact contents of the research frontiers are included but not limited to ocrelizumab, fingolimod and other monoclonal antibodies, fumaric acid ester, cladribine tablet, aHSCT, and other interventions of randomized controlled trials (RCTs); the impact of mRNA COVID-19 vaccination on MS patients; TI, patient adherence, and other medical management issues; and continued exploration of biomarkers for more accurate disease classification based on the existing clinical indication classification.

Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-ß1-NF-κB-MMP9 axis.

Background: Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-ß1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-ß1 hastens the invasive outgrowth of TNBC cells at the molecular level. Methods: LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively. Results: Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-κB (NF-κB). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-ß activated kinase 1 (TAK1) were required for the activation of NF-κB through Iκß kinase kinase (IKKα/ß) phosphorylation. Conclusion: Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-ß1-TRAF4-TAK1-IKKα/ß-Iκßα-NF-κB-MMP9, is crucial for TNBC cell invasiveness.

Haploidentical Hematopoietic Stem Cell Transplantation for Paediatric Patients with X-linked Lymphoproliferative Syndrome.

The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival.

The genomes of seven economic Caesalpinioideae trees provide insights into polyploidization history and secondary metabolite biosynthesis.

The Caesalpinioideae subfamily contains many well-known trees that are important for economic sustainability and human health, but a lack of genomic resources has hindered their breeding and utilization. Here, we present chromosome-level reference genomes for the two food and industrial trees Gleditsia sinensis (921 Mb) and Biancaea sappan (872 Mb), the three shade and ornamental trees Albizia julibrissin (705 Mb), Delonix regia (580 Mb), and Acacia confusa (566 Mb), and the two pioneer and hedgerow trees Leucaena leucocephala (1338 Mb) and Mimosa bimucronata (641 Mb). Phylogenetic inference shows that the mimosoid clade has a much higher evolutionary rate than the other clades of Caesalpinioideae. Macrosynteny comparison suggests that the fusion and breakage of an unstable chromosome are responsible for the difference in basic chromosome number (13 or 14) for Caesalpinioideae. After an ancient whole-genome duplication (WGD) shared by all Caesalpinioideae species (CWGD, ∼72.0 million years ago [MYA]), there were two recent successive WGD events, LWGD-1 (16.2-19.5 MYA) and LWGD-2 (7.1-9.5 MYA), in L. leucocephala. Thereafter, ∼40% gene loss and genome-size contraction have occurred during the diploidization process in L. leucocephala. To investigate secondary metabolites, we identified all gene copies involved in mimosine metabolism in these species and found that the abundance of mimosine biosynthesis genes in L. leucocephala largely explains its high mimosine production. We also identified the set of all potential genes involved in triterpenoid saponin biosynthesis in G. sinensis, which is more complete than that based on previous transcriptome-derived unigenes. Our results and genomic resources will facilitate biological studies of Caesalpinioideae and promote the utilization of valuable secondary metabolites.

Discovery of Potent, Selective, and Orally Available IRE1α Inhibitors Demonstrating Comparable PD Modulation to IRE1 Knockdown in a Multiple Myeloma Model.

The lack of selective and safe in vivo IRE1α tool molecules has limited the evaluation of IRE1α as a viable target to treat multiple myeloma. Focus on improving the physicochemical properties of a literature compound by decreasing lipophilicity, molecular weight, and basicity allowed the discovery of a novel series with a favorable in vitro safety profile and good oral exposure. These efforts culminated in the identification of a potent and selective in vivo tool compound, G-5758, that was well tolerated following multiday oral administration of doses up to 500 mg/kg. G-5758 demonstrated comparable pharmacodynamic effects to induced IRE1 knockdown as measured by XBP1s levels in a multiple myeloma model (KMS-11).

Elevated CO2 exacerbates the risk of methylmercury exposure in consuming aquatic products: Evidence from a complex paddy wetland ecosystem.

Elevated CO2 levels and methylmercury (MeHg) pollution are important environmental issues faced across the globe. However, the impact of elevated CO2 on MeHg production and its biological utilization remains to be fully understood, particularly in realistic complex systems with biotic interactions. Here, a complete paddy wetland microcosm, namely, the rice-fish-snail co-culture system, was constructed to investigate the impacts of elevated CO2 (600 ppm) on MeHg formation, bioaccumulation, and possible health risks, in multiple environmental and biological media. The results revealed that elevated CO2 significantly increased MeHg concentrations in the overlying water, periphyton, snails and fish, by 135.5%, 66.9%, 45.5%, and 52.1%, respectively. A high MeHg concentration in periphyton, the main diet of snails and fish, was the key factor influencing the enhanced MeHg in aquatic products. Furthermore, elevated CO2 alleviated the carbon limitation in the overlying water and proliferated green algae, with subsequent changes in physico-chemical properties and nutrient concentrations in the overlying water. More algal-derived organic matter promoted an enriched abundance of Archaea-hgcA and Deltaproteobacteria-hgcA genes. This consequently increased the MeHg in the overlying water and food chain. However, MeHg concentrations in rice and soil did not increase under elevated CO2, nor did hgcA gene abundance in soil. The results reveal that elevated CO2 exacerbated the risk of MeHg intake from aquatic products in paddy wetland, indicating an intensified MeHg threat under future elevated CO2 levels.

Design, synthesis and evaluation of novel prostate-specific membrane antigen-targeted aryl [18F]fluorosulfate PET tracers.

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.

Experimental and theoretical studies on the compatibility of DNTF and typical hydrocarbon polymer binders.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

Caffeine: a potential mechanism for anti-obesity.

Obesity refers to the excessive accumulation of fat caused by a long-term imbalance between energy intake (EI) and energy expenditure (EE). Over recent years, obesity has become a major public health challenge. Caffeine is a natural product that has been demonstrated to exert anti-obesity effects; however, the mechanisms responsible for the effect of caffeine on weight loss have yet to be fully elucidated. Most obesity-related deaths are due to cardiovascular disease. Recent research has demonstrated that caffeine can reduce the risk of death from cardiovascular disease; thus, it can be hypothesized that caffeine may represent a new therapeutic agent for weight loss. In this review, we synthesize data arising from clinical and animal studies over the last decade and discuss the potential mechanisms by which caffeine may induce weight loss, focusing particularly on increasing energy consumption, suppressing appetite, altering lipid metabolism, and influencing the gut microbiota. Finally, we summarize the major challenges associated with caffeine and anti-obesity research and highlight possible directions for future research and development.

A deep learning based multi-model approach for predicting drug-like chemical compound's toxicity.

Ensuring the safety and efficacy of chemical compounds is crucial in small-molecule drug development. In the later stages of drug development, toxic compounds pose a significant challenge, losing valuable resources and time. Early and accurate prediction of compound toxicity using deep learning models offers a promising solution to mitigate these risks during drug discovery. In this study, we present the development of several deep-learning models aimed at evaluating different types of compound toxicity, including acute toxicity, carcinogenicity, hERG_cardiotoxicity (the human ether-a-go-go related gene caused cardiotoxicity), hepatotoxicity, and mutagenicity. To address the inherent variations in data size, label type, and distribution across different types of toxicity, we employed diverse training strategies. Our first approach involved utilizing a graph convolutional network (GCN) regression model to predict acute toxicity, which achieved notable performance with Pearson R 0.76, 0.74, and 0.65 for intraperitoneal, intravenous, and oral administration routes, respectively. Furthermore, we trained multiple GCN binary classification models, each tailored to a specific type of toxicity. These models exhibited high area under the curve (AUC) scores, with an impressive AUC of 0.69, 0.77, 0.88, and 0.79 for predicting carcinogenicity, hERG_cardiotoxicity, mutagenicity, and hepatotoxicity, respectively. Additionally, we have used the approved drug dataset to determine the appropriate threshold value for the prediction score in model usage. We integrated these models into a virtual screening pipeline to assess their effectiveness in identifying potential low-toxicity drug candidates. Our findings indicate that this deep learning approach has the potential to significantly reduce the cost and risk associated with drug development by expediting the selection of compounds with low toxicity profiles. Therefore, the models developed in this study hold promise as critical tools for early drug candidate screening and selection.

Environmental exposure and child health in China.

Chinese children are exposed to broad environmental risks ranging from well-known hazards, such as pesticides and heavy metals, to emerging threats including many new man-made chemicals. Although anecdotal evidence suggests that the exposure levels in Chinese children are substantially higher than those of children in developed countries, a systematic assessment is lacking. Further, while these exposures have been linked to a variety of childhood diseases, such as respiratory, endocrine, neurological, behavioral, and malignant disorders, the magnitude of the associations is often unclear. This review provides a current epidemiologic overview of commonly reported environmental contaminants and their potential impact on children's health in China. We found that despite a large volume of studies on various topics, there is a need for more high-quality research and better-coordinated regional and national data collection. Moreover, prevention of such diseases will depend not only on training of environmental health professionals and enhanced research programs, but also on public education, legislation, and networking.

Multiplex nanozymatic biosensing of Salmonella on a finger-actuated microfluidic chip.

A colorimetric biosensor was elaboratively designed for fast, sensitive and multiplex bacterial detection on a single microfluidic chip using immune magnetic nanobeads for specific bacterial separation, immune gold@platinum palladium nanoparticles for specific bacterial labeling, a finger-actuated mixer for efficient immunoreaction and two coaxial rotatable magnetic fields for magnetic nanobead capture (outer one) and magnet-actuated valve control (inner one). First, preloaded bacteria, nanobeads and nanozymes were mixed through a finger actuator to form nanobead-bacteria-nanozyme conjugates, which were captured by the outer magnetic field. After the inner magnetic field was rotated to successively wash the conjugates and push the H2O2-TMB substrate for resuspending these conjugates, colorless TMB was catalyzed into blue TMBox products, followed by color analysis using ImageJ software for bacterial determination. This simple biosensor enabled multiplex Salmonella detection as low as 9 CFU per sample in 45 min.

Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the digestive tract. Rauwolfia polysaccharide (Rau) has therapeutic effects on colitis in mice, but its mechanism of action needs to be further clarified. In the study, we explored the effect of Rau on the UC cell model induced by Lipopolysaccharide (LPS). METHODS: We constructed a UC cell model by stimulating HT-29 cells with LPS. Dextran sodium sulfate (DSS) was used to induce mice to construct an animal model of UC. Subsequently, we performed Rau administration on the UC cell model. Then, the therapeutic effect of Rau on UC cell model and was validated through methods such as Cell Counting Kit-8 (CCK8), Muse, Quantitative real­time polymerase chain reaction (RT-qPCR), Western blotting, and Enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that Rau can promote the proliferation and inhibit the apoptosis of the HT-29 cells-induced by LPS. Moreover, we observed that Rau can inhibit the expression of NOS2/JAK2/STAT3 in LPS-induced HT-29 cells. To further explore the role of NOS2 in UC progression, we used siRNA technology to knock down NOS2 and search for its mechanism in UC. The results illustrated that NOS2 knockdown can promote proliferation and inhibit the apoptosis of LPS-induced HT-29 cells by JAK2/STAT3 pathway. In addition, in vitro and in vivo experiments, we observed that the activation of the JAK2/STAT3 pathway can inhibit the effect of Rau on DSS-induced UC model. CONCLUSION: In short, Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway. This study provides a theoretical clue for the treatment of UC by Rau.

Effectiveness of Low-frequency Pulse Electrical Stimulation Combined with Dexamethasone in Treating Facial Nerve Paralysis and Its Impact on Facial Nerve Function and Electromyography.

Objective: This study aimed to evaluate the efficacy of adjunct low-frequency pulse electrical stimulation alongside dexamethasone in the treatment of facial nerve paralysis and its subsequent effects on facial nerve function and electromyographic parameters. With the aim of addressing a knowledge gap in the field, this research provides valuable insights into the potential benefits of combining these treatments and their impact on clinical outcomes, facial nerve functionality, and electromyographic dynamics. Methods: A cohort of 66 patients with facial nerve paralysis treated at our institution between April 2018 and November 2021 were randomly assigned to either an observation (n=33) or an experimental group (n=33). The observation group received standard pharmacotherapy, including Western medications and Daqinjiao decoction, along with dexamethasone. The experimental group was administered low-frequency pulse electrical stimulation in addition to the observation group's regimen. Outcomes assessed were clinical efficacy, facial nerve paralysis scoring, facial nerve functional scoring and indices, electromyographic latency, amplitude ratios between affected and unaffected sides, as well as any adverse events. Results: The experimental group demonstrated a significant improvement over the observation group in clinical treatment outcomes, facial nerve paralysis scores, and facial nerve function scores (P < .05 for all). Furthermore, electromyographic analysis revealed shorter latency periods and greater amplitude ratios in the experimental group's facial muscles post-treatment (P < .05). No significant difference was observed in the incidence of adverse reactions between the two groups (P > .05). Conclusion: The integration of low-frequency pulse electrical stimulation with dexamethasone therapy significantly ameliorates the severity of facial nerve paralysis, enhances facial nerve function, and improves electromyographic signals in facial muscles without increasing adverse effects. These findings support the clinical value and safety of this combined treatment approach for facial nerve paralysis, suggesting its suitability for broader clinical application. These results suggest that this combined treatment approach holds promise for broader clinical application, potentially providing a more effective and safer therapeutic option for patients with facial nerve paralysis. Implementing this approach in clinical practice may lead to improved treatment outcomes, better functional recovery, and enhanced quality of life for affected individuals.