Rhodium-catalyzed synthesis of Si-stereogenic alkoxysilanes and silyl enol ethers via hydrosilylation of carbonyl compounds.

A highly efficient rhodium-catalyzed asymmetric hydrosilylation of aldehydes, ketones, and α,ß-unsaturated ketones with dihydrosilanes is developed, that allows the rapid assembly of a variety of Si-stereogenic alkoxysilanes and silyl enol ethers in good yields and enantioselectivities under mild conditions. The applicability of this methodology was demonstrated by a series of stereospecific transformations to construct diverse Si-stereogenic derivatives.

Improvement of water quality through coordinated multi-trophic level biomanipulations: Application to a subtropical emergency water supply lake.

Artificial emergency water source lakes have been built in most cities in the middle and lower reaches of the Yangtze River, China, to ensure water safety for residents. However, these new ecosystems are prone to algal blooms or other degraded water quality conditions. A newly built water supply lake in the lower reaches of the Yangtze River was selected as a model system to test whether the coordinated manipulation of fish and submerged macrophyte communities could enhance ecosystem function and quality. The coordinated manipulations spanned a five-year period, aiming to enhance both top-down and bottom-up control of phytoplankton. As a result of these manipulations, the catch per unit effort of small-bodied zooplanktivorous fishes decreased by >95 % from year two and remained low. The coverage and biomass of submerged macrophytes increased year by year. Water transparency increased from 1.07 to 3.33 m. Total phosphorus and total nitrogen showed a decreasing trend (not significant though). The annual mean biomass of Cyanophyta, Chlorophyta and Bacillariophyta decreased from 2.99 to 0.03 mg/L, 3.90 to 0.16 mg/L, and 3.50 to 0.3 mg/L, respectively. The biomass of phytoplankton in different groups decreased in all four seasons. The annual mean biomass of Cladocera and Copepoda remained low. The biomass of Cladocera and Copepoda decreased in summer, fall, and winter. The Ecosystem Health Index - increased from 15.9 to 32.0. The pros and cons of the various top-down and bottom-up control measures employed are discussed. This research presents a valuable case study on the enhancement of ecosystem structure and function in newly constructed emergency water supply lakes and offers insights into the restoration of other subtropical shallow lakes.

Prognostic prediction and immune infiltration analysis based on lysosome and senescence state identifies MMP12 as a novel therapy target in gastric cancer.

BACKGROUND AND AIMS: As humans undergo the aging process, they become more vulnerable to various types of cancers, including gastric cancer (GC), which is frequently associated with aging. The senescent phenotype is closely linked to lysosomes, but research on the combined impact of senescence and lysosomes on GC prognosis is scarce. METHODS: To construct and validate a prognostic model for gastric cancer (GC), we obtained gene expression and clinical data of GC patients from Cancer Genome Atlas (TCGA) databases. We employed Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression for model construction and ConsensusClusterPlus R package for generating cluster heatmaps. The model's predictive ability was evaluated through Kaplan-Meier survival analysis and ROC curve analysis. Our analysis included an assessment of the senescence and lysosome state using expression profiles and immune infiltration analysis through CIBERSORT methods. Finally, we validated potential gene targets through cellular experiments. RESULTS: "In this research, we discovered two subtypes of gastric cancer (GC), Cluster 1 and Cluster 2. These subtypes are characterized by the presence of lysosomes and senescence, and we have identified distinct molecular features unique to each subtype. We observed that Cluster 2 had a lower survival prognosis compared to Cluster 1. Additionally, we have developed a risk prediction model that takes into consideration the presence of lysosomes and senescence. Patients in the high-risk group, as predicted by our model, experienced shorter survival times. Further analysis included immune infiltration, immune checkpoint, and chemotherapy evaluation of GC patients. We have displayed the frequency of mutations and copy number variations (CNVs) in visual formats. Our cellular experiments demonstrated that the MMP12 gene serves as a protective factor in GC cells." CONCLUSIONS: In conclusion, we have clarified the extensive relationship between lysosomes and senescence in GC and developed a risk signature to forecast the prognosis of GC patients. MMP12 could be a promising protective factor for GC patients and might present a novel concept for anticipating the efficacy of targeted therapies and immunotherapies in GC patients.

Catalytic Asymmetric Construction of C- and Si-Stereogenic Silacyclopentanes via Hydrosilylation of Arylmethylenecyclopropanes.

Silacycles have exhibited significant potential for application in the fields of medicinal chemistry, agrochemistry, and materials science. Accordingly, the development of effective methods for synthesizing these compounds has attracted increasing attention. Here, we report an efficient Cu-catalyzed enantioselective hydrosilylation of arylmethylenecyclopropanes with hydrosilanes, that allows the rapid assembly of various enantioenriched carbon- and silicon-stereogenic silacyclopentanes in good yields with excellent enantioselectivities and diastereoselectivities under mild conditions. Further stereospecific transformation of the Si-H bond on the chiral silicon center expands the diversity of these C- and Si-stereogenic silacyclopentanes.

Promising therapy for neuroendocrine prostate cancer: current status and future directions.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of castration-resistant prostate cancer. It is characterized by low or no expression of the androgen receptor (AR), activation of AR-independent signaling, and increased neuroendocrine phenotype. Most of NEPC is induced by treatment of androgen deprivation therapy and androgen receptor pathway inhibitors (ARPIs). Currently, the treatment of NEPC follows the treatment strategy for small-cell lung cancer, lacking effective drugs and specific treatment options. This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (zeste homolog 2 inhibitors, lysine-specific demethylase 1 inhibitors), aurora kinase A inhibitors, poly-ADP-ribose polymerase inhibitors, delta-like ligand 3 targeted therapies, a combination of immunotherapies, etc. Other promising targets and future directions are also discussed in this review. These novel targets and therapies may provide new opportunities for the treatment of NEPC.

This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (EZH2 inhibitors, LSD-1 inhibitors), AURKA inhibitors, PARP inhibitors, and DLL3 targeted therapies, and combination of immunotherapies, etc. These novel targets and therapies may provide new opportunities in the treatment of NEPC.

Efficacy and survival outcome of allogeneic stem-cell transplantation in multiple myeloma: meta-analysis in the recent 10 years.

Introduction: Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM. Methods: We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT in MM patients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted meta-analysis in the NDMM/frontline setting and RRMM/salvage setting independently. Results: The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively. Discussion: Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/ frontline setting. Conclusion: Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients.

Clinicopathological features of two cases of ETV6-NTRK3 rearranged papillary thyroid carcinoma: a case report.

Rearrangements involving the neurotrophic-tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2, and NTRK3) have been identified as drivers in a wide variety of human cancers. However, the association between NTRK rearranged thyroid carcinoma and clinicopathological characteristics has not yet been established. In our study, we retrospectively reviewed medical records of thyroid cancer patients and identified 2 cases with NTRK rearrangement, no additional molecular alterations were observed in either of these cases. The fusion of the rearrangement in both cases was ETV6(E4)::NTRK3(E14). By analyzing the clinicopathological features of these two cases, we found that both were characterized by multiple tumor nodules, invasive growth, and central lymph node metastases, indicating the follicular subtype of papillary thyroid carcinoma. Immunohistochemical staining profiles showed CD56-, CK19+, Galectin-3+, HBME1+. These clinicopathological features suggest the possibility of ETV6-NTRK3 rearranged thyroid carcinoma and highlight the importance of performing gene fusion testing by FISH or NGS for these patients.

Global trends and projections of colorectal, esophageal and stomach cancer burden among youth associated with diet: A analysis of 204 countries and territories from 1990 to 2019 and until 2040.

BACKGROUND: Unhealthy diets significantly contribute to stomach, colorectal and esophageal cancer burden globally. Western diets high in processed and red meats promote carcinogenesis in these gastrointestinal cancers. However, adolescent and young adult (AYA) patients' unique needs regarding these cancers have been neglected. METHODS: Data from the 2019 Global Burden of Disease study was used to quantify stomach, colorectal and esophageal cancer burden among AYAs from 1990 to 2040 across 204 countries. Correlations between the burden of these cancers and the Socio-demographic Index were examined. RESULTS: High SDI locations experienced the largest reduction in cancer DALY rate change from 1990 to 2019 (-22% [-12 to -33]), compared to a small increase in low-middle SDI regions. Middle SDI areas saw the largest reduction in DALY rate change from 1990 to 2019 (-62% [-32 to -75]), compared to a small decrease in low-middle SDI locations (-9% [-27 to 10]) in esophageal cancer. From 1990-2019, stomach cancer deaths and DALYs declined across all SDI regions, with the largest reductions in high SDI locations (-61% [-57 to -69]) and smallest in low-middle SDI areas (-25% [-13 to -34]). Colorectal cancer deaths and DALYs rose across all SDI regions except high SDI locations, which showed a slight decrease. CONCLUSION: This study demonstrates the evolving global burden of stomach, colorectal and esophageal cancers among AYAs. The highest burden was in high-middle and high SDI regions, underscoring the need to prioritize initiatives targeting these gastrointestinal malignancies in youth.

Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol.

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.

The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia. However, the role of the miR-15a/16-1 cluster in neurotrauma is poorly explored. Here, we report that genetic deletion of the miR-15a/16-1 cluster facilitated the recovery of sensorimotor and cognitive functions, alleviated white matter/gray matter lesions, reduced cerebral glial cell activation, and inhibited infiltration of peripheral blood immune cells to brain parenchyma in a murine model of TBI when compared with WT controls. Moreover, intranasal delivery of the miR-15a/16-1 antagomir provided similar brain-protective effects conferred by genetic deletion of the miR-15a/16-1 cluster after experimental TBI, as evidenced by showing improved sensorimotor and cognitive outcomes, better white/gray matter integrity, and less inflammatory responses than the control antagomir-treated mice after brain trauma. miR-15a/16-1 genetic deficiency and miR-15a/16-1 antagomir also significantly suppressed inflammatory mediators in posttrauma brains. These results suggest miR-15a/16-1 as a potential therapeutic target for TBI.

Limit state equation and failure pressure prediction model of pipeline with complex loading.

Assessing failure pressure is critical in determining pipeline integrity. Current research primarily concerns the buckling performance of pressurized pipelines subjected to a bending load or axial compression force, with some also looking at the failure pressure of corroded pipelines. However, there is currently a lack of limit state models for pressurized pipelines with bending moments and axial forces. In this study, based on the unified yield criterion, we propose a limit state equation for steel pipes under various loads. The most common operating loads on buried pipelines are bending moment, internal pressure, and axial force. The proposed limit state equation for intact pipelines is based on a three-dimensional pipeline stress model with complex load coupling. Using failure data, we investigate the applicability of various yield criteria in assessing the failure pressure of pipelines with complex loads. We show that the evaluation model can be effectively used as a theoretical solution for assessing the failure pressure in such circumstances and for selecting appropriate yield criteria based on load condition differences.

Engineering non-conventional yeast Rhodotorula toruloides for ergothioneine production.

BACKGROUND: Ergothioneine (EGT) is a distinctive sulfur-containing histidine derivative, which has been recognized as a high-value antioxidant and cytoprotectant, and has a wide range of applications in food, medical, and cosmetic fields. Currently, microbial fermentation is a promising method to produce EGT as its advantages of green environmental protection, mild fermentation condition, and low production cost. However, due to the low-efficiency biosynthetic process in numerous cell factories, it is still a challenge to realize the industrial biopreparation of EGT. The non-conventional yeast Rhodotorula toruloides is considered as a potential candidate for EGT production, thanks to its safety for animals and natural ability to synthesize EGT. Nevertheless, its synthesis efficiency of EGT deserves further improvement. RESULTS: In this study, out of five target wild-type R. toruloides strains, R. toruloides 2.1389 (RT1389) was found to accumulate the highest EGT production, which could reach 79.0 mg/L at the shake flask level on the 7th day. To achieve iterative genome editing in strain RT1389, CRISPR-assisted Cre recombination (CACR) method was established. Based on it, an EGT-overproducing strain RT1389-2 was constructed by integrating an additional copy of EGT biosynthetic core genes RtEGT1 and RtEGT2 into the genome, the EGT titer of which was 1.5-fold increase over RT1389. As the supply of S-adenosylmethionine was identified as a key factor determining EGT production in strain RT1389, subsequently, a series of gene modifications including S-adenosylmethionine rebalancing were integrated into the strain RT1389-2, and the resulting mutants were rapidly screened according to their EGT production titers with a high-throughput screening method based on ergothionase. As a result, an engineered strain named as RT1389-3 was selected with a production titer of 267.4 mg/L EGT after 168 h in a 50 mL modified fermentation medium. CONCLUSIONS: This study characterized the EGT production capacity of these engineered strains, and demonstrated that CACR and high-throughput screening method allowed rapid engineering of R. toruloides mutants with improved EGT production. Furthermore, this study provided an engineered RT1389-3 strain with remarkable EGT production performance, which had potential industrial application prospects.

Application of Carbon Nanoparticles in Transoral Endoscopic Thyroidectomy Vestibular Approach for Unilateral Papillary Thyroid Cancer.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied technology. Carbon nanoparticles (CNs) are novel lymph node tracers that have been widely used in China to help remove central lymph nodes (CLNs) and protect the parathyroid glands (PGs) in open thyroid cancer surgery. This study is to evaluate the effectiveness and safety of CNs in TOETVA. MATERIALS AND METHODS: A total of 158 patients who underwent TOETVA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The participants were divided into a CNs group (n=88) and a control group (n=70), based on whether they received a intraoperative injection of CNs or not. Meanwhile, the CNs group were additionally divided into 2 subgroups, leakage subgroup (n=26) and standard subgroup (n=62). The 2 groups and subgroups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: All common metrics had no significant differences were found between the CNs group and the control group ( P >0.05). The standard subgroup of CNs group had advantage over the control group on PGs identification (59/62 vs. 59/70 for superior PG, 56/62 vs. 52/70 for inferior PG, P <0.05). Moreover, the standard subgroup harvested more CLNs than the control group (8.97±2.96 vs. 7.47±2.93, P <0.05). More operation time was spent on the leakage subgroup of CNs group than the control group (160.00±17.61 vs. 140.00±13.32, P <0.05). Meanwhile, the leakage subgroup had disadvantage on intraoperative hemorrhage (26.15±10.80 vs. 21.21±7.09, P <0.05) and hospital durations (4.96±0.72 vs. 4.57±0.69, P <0.05). Furthermore, the leakage group identified fewer inferior PG than the control group (7/26 vs. 52/70, P <0.05). Contrary to the standard subgroup, the CLNs of the leakage subgroup was also unsatisfactory compared with the control group (4.96±1.84 vs. 7.47±2.93, P <0.05). CONCLUSIONS: The application of CNs suspension tracing technology has a definite effect in TOETVA. It can improve the thoroughness of lymph node dissection in the central region and enhance recognition of the PG. However, refined extracapsular anatomy is indispensable to prevent CN leakage. Leaked CNs will also be counterproductive to the operation.

A multifunctional Ag NPs/guar gum hydrogel as versatile platform for catalysts, antibacterial agents, and construction of oil-water separation interfaces.

The frequently encountered wastewater contaminations, including soluble aromatic compound and dye pollutants, pathogenic bacteria, and insoluble oils, have resulted in significant environmental and human health issues. It poses a challenge to utilize identical materials for the treatment of complex wastewater. Herein, in this research, multifunctional Ag NPs/guar gum hybrid hydrogels were fabricated using a facile in situ reduction and self-crosslinking method for efficient remediation of complex wastewater. The Ag NPs/guar gum hybrid hydrogel showed remarkable remodeling, adhesive, and self-healing characteristics, which was favorable for its versatile applications. The combination of Ag NPs with the guar gum skeleton endowed the hybrid hydrogel with exceptional catalytic activity for reducing aromatic compounds and dye pollutants, as well as remarkable antibacterial efficacy against pathogenic bacteria. In addition, the Ag NPs/guar gum hybrid hydrogel could be employed to coat a variety of substrates, including cotton fabrics and stainless steel meshes. The hydrogel coated cotton fabrics and meshes presented superhydrophilicity/underwater superoleophobicity, excellent antifouling capacity, and outstanding recyclability, which could be successfully applied for efficient separation of oil-water mixtures. The findings of this work provide a feasible and cost-effective approach for the remediation of intricate wastewater.

The Brachypodium distachyon DREB transcription factor BdDREB-39 confers oxidative stress tolerance in transgenic tobacco.

Key message BdDREB-39 is a DREB/CBF transcription factor, localized in the nucleus with transactivation activity, and BdDREB-39-overexpressing transgenic yeasts and tobacco enhanced the tolerance to oxidative stress.Abstract The DREB/CBF transcription factors are generally recognized to play an important factor in plant growth, development and response to various abiotic stresses. However, the mechanism of DREB/CBFs in oxidative stress response is largely unknown. This study isolated a DREB/CBF gene BdDREB-39 from Brachypodium distachyon (B. distachyon). Multiple sequence alignment and phylogenetic analysis showed that BdDREB-39 was closely related to the DREB proteins of oats, barley, wheat and rye and therefore its study can provide a reference for the excavation and genetic improvement of BdDREB-39 or its homologs in its closely related species. The transcript levels of BdDREB-39 were significantly up-regulated under H2O2 stress. BdDREB-39 was localised in the nucleus and functioned as a transcriptional activator. Overexpression of BdDREB-39 enhanced H2O2 tolerance in yeast. Transgenic tobaccos with BdDREB-39 had higher germination rates, longer root, better growth status, lesser reactive oxygen species (ROS) and malondialdehyde (MDA), and higher superoxide dismutase (SOD) and peroxidase (POD) activities than wild type (WT). The expression levels of ROS-related and stress-related genes were improved by BdDREB-39. In summary, these results revealed that BdDREB-39 can improve the viability of tobacco by regulating the expression of ROS and stress-related genes, allowing transgenic tobacco to accumulate lower levels of ROS and reducing the damage caused by ROS to cells. The BdDREB-39 gene has the potential for developing plant varieties tolerant to stress.

[Inhibition of Autophagy Augments the Anticancer Activity of KPT-330 in Mantle Cell Lymphoma Cells].

OBJECTIVE: To investigate the influence of novel CRM1 inhibitor KPT-330 on the autophagy of mantle cell lymphoma (MCL) cells, and effect of KPT-330 on the prolifiration of MCL cells in the presence or absence of autophagy inhibitor. METHODS: CCK-8 assay was used to detect the effect of KPT-330 on MCL cell lines Z-138， Jeko-1， Granta-519， Rec-1. The effect of KPT-330 on autophagy features were determined by detecting acidic vesicular organelles (AVO) by MDC staining under fluorescence microscope and detecting protein expression of LC3B-II assessed by Western blot. Further combined application of lysosomal inhibitor Chloroquine (CQ) was used to observe its effect on the increase of LC3B-Ⅱ caused by KPT-330. CalcuSyn 2.0 software was used to detected the Combination index (CI) of KPT-330 combined with CQ. RESULTS: The proliferation of MCL cell lines （Z-138, Jeko-1, Grant-519, Rec-1） could be inhibited by KPT-330 in a dose-dependent manner (r =0.930, 0.946, 0.691, 0.968 respectively). The number of acidic vesicular organelles (AVO) and the expression of LC3B-II were increased in KPT-330 treated Jeko-1 and Granta-519 cells in a dose-dependent manner (r Jeko-1=0.993, r Granta-519=0.971). LC3B-II protein amounts still increased upon KPT-330 treatment with the existence of lysosomal inhibitor CQ in Jeko-1 and Granta-519 cells, which was higher than CQ or KPT-330 single drug group. The combination of KPT-330 and CQ produced the synergistic effects on cells proliferation inhibition with CalcuSyn 2.0 analysis. CONCLUSION: KPT-330 can inhibit MCL cell proliferation and induce autophagy. KPT-330 combined with autophagy inhibitor CQ could produce synergistic anti MCL effects, providing experimental basis for clinical combination therapy.

The down-regulation of GADD45B leads to a conversion of cellular oxidative phosphorylation to glycolysis and promotes the progression of bladder cancer.

Background: The predominant feature of cancer cells during the process of carcinogenesis is the inclination towards glycolytic metabolism rather than mitochondrial oxidative phosphorylation. Nevertheless, there is a scarcity of research investigating the correlation between bladder cancer and mitochondrial energy metabolism. Methods: A qPCR array comprising 90 genes associated with mitochondrial oxidative phosphorylation was employed to discern metabolic disparities between three sets of bladder cancer tissue and adjacent normal tissue. Wound healing and transwell assays were utilized to assess cell migration and invasion capabilities, respectively. Colony formation assays were conducted to ascertain the tumorigenic potential of the cells. The proliferative capacity of the cells was examined through in vitro CCK-8 assays. Additionally, nude mouse models were established to evaluate the impact of bladder tumor cells on in vivo proliferation. The Seahorse XFe96 Analyzer was utilized to quantify mitochondrial oxidative phosphorylation, while the levels of glucose-6-phosphate and pyruvate were assessed to evaluate glycolysis. Results: Examination of qPCR array data demonstrated a noteworthy inhibition of mitochondrial oxidative phosphorylation in bladder cancer tissue, as evidenced by the down-regulation of a majority of genes associated with mitochondrial energy metabolism. Notably, GADD45B may potentially exert a significant influence on bladder cancer development, warranting further investigation. The down-regulation of GADD45B in bladder cancer cells resulted in impaired mitochondrial respiration and elevated levels of glycolysis, thereby enhancing cell migration and invasion. Conversely, up-regulation of GADD45B had the opposite effect. Furthermore, over-expression of GADD45B inhibited tumor proliferation and tumorigenesis in both in vitro and in vivo settings. Conclusion: These findings from our study indicate that the down-regulation of GADD45B promotes the shift of cell mitochondrial oxidative phosphorylation towards glycolysis, thereby facilitating the progression of bladder cancer.

Community-based rehabilitation services implemented by multidisciplinary teams among adults with stroke: a scoping review with a focus on Chinese experience.

BACKGROUND: Despite the growing interest in hospital rehabilitation services for communities, studies on existing community-based rehabilitation (CBR) services remain scarce owing to limitations in the development of community health services and regional cultural diversity. As a guaranteed measure for ensuring the quality of rehabilitation services and achieving the desired service outcomes, clear roles and responsibilities in multidisciplinary teams and effective service delivery are particularly important. OBJECTIVE: This scoping review aimed to determine the scope of community stroke rehabilitation programs involving existing multidisciplinary teams and to analyze the implementation content and implementers' functional roles to provide guidance for future CBR programs. METHODS: The scoping review design followed the methodology of the Joanna Briggs Institute and was based on the normative scoping review framework proposed by Arksey and O'Malley. The comprehensive CBR framework was proposed by World Health Organization-guided data charting and analysis. RESULTS: Of the 22,849 identified citations, 74 studies were included, consisting of 6,809 patients with stroke and 49 primary caregivers, most of whom were from China. The most common working mode in CBR programs was a dual approach involving both healthcare professionals in medical institutions and community healthcare professionals. The number of programs in each discipline was in the following descending order: nursing, medical care, rehabilitation, psychology, nutrition, and public health. Among these, multidisciplinary teams comprising medical, nursing, and rehabilitation disciplines were the most common, with a total of 29 programs. Disciplinary members were mainly responsible for implementing their respective disciplinary content, with physicians providing guidance for the programs. More than 82.4% of the studies reported 2-4 intervention strategies. The intervention forms of rehabilitation content were the most diverse, whereas preventive interventions were more homogeneous than others. Physical function and socio-psychological measurements were the most commonly reported outcomes. CONCLUSION: CBR services implemented by multidisciplinary teams can effectively achieve functional and emotional improvement in patients with stroke, and nurses are the most involved in implementation, especially in community settings. The results further emphasize the importance of strengthening the exploration of nurses' maximum potential to implement CBR plans in future practice. TRIAL REGISTRATION: The registration information for this scoping review can be found at osf.io/pv7tg.

Risk of Systemic Inflammatory Response Syndrome Following Preoperative Glucocorticoids Administration in Patients After Percutaneous Nephrolithotomy: A Retrospective Cohort Study.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. METHODS: A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31-4.55, p = 0.005). CONCLUSION: Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL.

Systemic inflammatory response syndrome (SIRS) is a frequent and severe complication in patients underwent percutaneous nephrolithotomy (PCNL), which can be challenging to diagnose early, potentially leading to delayed treatment. Identifying SIRS risk factors and promptly treating high-risk patients is crucial. Glucocorticoids are commonly used to prevent SIRS in clinical practice, and this study aims to investigate whether preoperative glucocorticoid administration is associated with SIRS after PCNL. In total, 1259 patients underwent PCNL and were enrolled in the study. The study utilized both propensity score matching (PSM) analysis and regression analysis to identify risk factors for post-PCNL SIRS. The incidence of SIRS after PCNL was 9.6 % in the study and patients with postoperative SIRS had longer hospital stays and higher hospital costs. After minimizing the potential influence of confounding factors through the use of PSM, we found a significant association between the preoperative use of glucocorticoids and the occurrence of SIRS in patients undergoing PCNL. Based on our analysis, we can conclude that the preoperative administration of glucocorticoids represents an independent risk factor for the development of SIRS in these patients.

Co-augmentation of a transport gene mfsT1 in Mycolicibacterium neoaurum with genome engineering to enhance ergothioneine production.

Ergothioneine (EGT) is a rare thiohistidine derivative with exceptional antioxidant properties. The blood level of EGT is considered highly reliable predictors for cardiovascular diseases and mortality, yet animals lack the ability to synthesize this compound. Free plasmids have been previously used to overexpress genes involved in the EGT biosynthetic pathway of Mycolicibacterium neoaurum. Here, we tentatively introduced a putative transporter gene mfsT1 into high-copy plasmids and sharply increased the ratio of extracellular EGT concentration from 18.7% to 44.9%. Subsequently, an additional copy of egtABCDE, hisG, and mfsT1 was inserted into the genome with a site-specific genomic integration tool of M. neoaurum, leading a 2.7 times increase in EGT production. Co-enhancing the S-adenosyl-L-methionine regeneration pathway, or alternatively, the integration of three copies of egtABCDE, hisG and mfsT1 into the genome further increased the total EGT yield by 16.1% (64.6 mg/L) and 21.7% (67.7 mg/L), respectively. After 168-h cultivation, the highest titer reached 85.9 mg/L in the latter strain with three inserted copies. This study provided a solid foundation for genome engineering to increase the production of EGT in M. neoaurum.