Trio preserves motor synapses and prolongs motor ability during aging.

The decline of motor ability is a hallmark feature of aging and is accompanied by degeneration of motor synaptic terminals. Consistent with this, Drosophila motor synapses undergo characteristic age-dependent structural fragmentation co-incident with diminishing motor ability. Here, we show that motor synapse levels of Trio, an evolutionarily conserved guanine nucleotide exchange factor (GEF), decline with age. We demonstrate that increasing Trio expression in adult Drosophila can abrogate age-dependent synaptic structural fragmentation, postpone the decline of motor ability, and maintain the capacity of motor synapses to sustain high-intensity neurotransmitter release. This preservative activity is conserved in transgenic human Trio, requires Trio Rac GEF function, and can also ameliorate synapse degeneration induced by depletion of miniature neurotransmission. Our results support a paradigm where the structural dissolution of motor synapses precedes and promotes motor behavioral diminishment and where intervening in this process can postpone the decline of motor function during aging.

Marcytoglobosins A and B, Cytochalasans from a Marine Sponge Associated Chaetomium globosum 162105 Fungus.

Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity. Among them, compounds 3-8 displayed antibacterial effects against Staphylococcus epidermidis, Bacillus thuringiensis, Pseudomonas syringae pv. Actinidiae, Vibrio alginolyticus, and Edwardsiella piscicida with minimum inhibitory concentration (MIC) values ranging from 10 to 25 µg/mL.

Complex Spatial Illumination Scheme Optimization of Backscattering Mueller Matrix Polarimetry for Tissue Imaging and Biosensing.

Polarization imaging and sensing techniques have shown great potential for biomedical and clinical applications. As a novel optical biosensing technology, Mueller matrix polarimetry can provide abundant microstructural information of tissue samples. However, polarimetric aberrations, which lead to inaccurate characterization of polarization properties, can be induced by uneven biomedical sample surfaces while measuring Mueller matrices with complex spatial illuminations. In this study, we analyze the detailed features of complex spatial illumination-induced aberrations by measuring the backscattering Mueller matrices of experimental phantom and tissue samples. We obtain the aberrations under different spatial illumination schemes in Mueller matrix imaging. Furthermore, we give the corresponding suggestions for selecting appropriate illumination schemes to extract specific polarization properties, and then provide strategies to alleviate polarimetric aberrations by adjusting the incident and detection angles in Mueller matrix imaging. The optimized scheme gives critical criteria for the spatial illumination scheme selection of non-collinear backscattering Mueller matrix measurements, which can be helpful for the further development of quantitative tissue polarimetric imaging and biosensing.

Synthesis and Biological Evaluation of New Dihydrofuro[3,2-b]piperidine Derivatives as Potent α-Glucosidase Inhibitors.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 µM) and 28 (IC50 = 0.5 µM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure-activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors.

Microtubule interacting and trafficking domain containing 1 deficiency leads to poor survival via tissue factor-mediated coagulation in bladder cancer.

BACKGROUND: Patients with cancer are at an increased risk of developing a hypercoagulative phenotype and venous thromboembolism. However, no clinical trial has yet confirmed that anticoagulant therapy improves cancer prognosis, and the mechanism underlying hypercoagulation in patients with bladder cancer is not well understood. OBJECTIVES: We hypothesized that the prognostic genes affect tumor progression via tumor-mediated coagulation. METHODS: We detected the most significant prognostic genes of bladder cancer with The Cancer Genome Atlas dataset and validated them in 2 Gene Expression Omnibus datasets and 1 ArrayExpress dataset. Immunohistochemical tests were performed on a cohort of 80 individuals to further examine the prognostic genes. For the most reliable prognostic gene, its influence on coagulation was evaluated with gene knockdown followed by next-generation sequencing and cellular and animal experiments. RESULTS: Depletion of microtubule interacting and trafficking domain containing 1 (MITD1), a major prognostic gene of bladder cancer, significantly increased the tissue factor (TF) expression. MITD1 deficiency led to cytokinesis arrest, which, in turn, promoted the TF expression via unfolded protein response and c-Jun. The knockdown of IRE1, an essential kinase of unfolded protein response or the inactivation of c-Jun using c-Jun N-terminal kinase inhibitors weakened MITD1 deficiency- or dithiothreitol-induced TF upregulation. Cells lacking MITD1 promoted coagulation and metastasis in the experimental metastasis assay. CONCLUSION: Our findings suggest the novel role of tumor prognostic genes upon the development of hypercoagulative phenotype and venous thromboembolism, thereby underlining the importance of anticoagulant therapy and shedding light on the therapeutic value of targeting MITD1 in bladder cancer.

Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge Dysidea arenaria.

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.

Ablation of Shank1 Protects against 6-OHDA-induced Cytotoxicity via PRDX3-mediated Inhibition of ER Stress in SN4741 Cells.

BACKGROUND: Postsynaptic density (PSD) is an electron-dense structure that contains various scaffolding and signaling proteins. Shank1 is a master regulator of the synaptic scaffold located at glutamatergic synapses, and has been proposed to be involved in multiple neurological disorders. METHODS: In this study, we investigated the role of shank1 in an in vitro Parkinson's disease (PD) model mimicked by 6-OHDA treatment in neuronal SN4741 cells. The expression of related molecules was detected by western blot and immunostaining. RESULTS: We found that 6-OHDA significantly increased the mRNA and protein levels of shank1 in SN4741 cells, but the subcellular distribution was not altered. Knockdown of shank1 via small interfering RNA (siRNA) protected against 6-OHDA treatment, as evidenced by reduced lactate dehydrogenase (LDH) release and decreased apoptosis. The results of RT-PCR and western blot showed that knockdown of shank1 markedly inhibited the activation of endoplasmic reticulum (ER) stress associated factors after 6-OHDA exposure. In addition, the downregulation of shank1 obviously increased the expression of PRDX3, which was accompanied by the preservation of mitochondrial function. Mechanically, downregulation of PRDX3 via siRNA partially prevented the shank1 knockdowninduced protection against 6-OHDA in SN4741 cells. CONCLUSION: In summary, the present study has provided the first evidence that the knockdown of shank1 protects against 6-OHDA-induced ER stress and mitochondrial dysfunction through activating the PRDX3 pathway.

Mesenchymal stem cells-derived extracellular vesicle-incorporated H19 attenuates cardiac remodeling in rats with heart failure.

Cardiac remodeling is manifested by hypertrophy and apoptosis of cardiomyocytes, resulting in the progression of cardiovascular diseases. Long noncoding RNAs (lncRNAs) serve as modifiers of cardiac remodeling. In this study, we aimed to explore the molecular mechanism of H19 shuttled by mesenchymal stem cells (MSC)-derived extracellular vesicles (EV) in cardiac remodeling upon heart failure (HF). Using the GEO database, H19, microRNA (miR)-29b-3p, and CDC42 were screened out as differentially expressed biomolecules in HF. H19 and CDC42 were elevated, and miR-29b-3p was decreased after MSC-EV treatment in rats subjected to ligation of the coronary artery. MSC-EV alleviated myocardial injury in rats with HF. H19 downregulation exacerbated myocardial injury, while miR-29b-3p inhibitor alleviated myocardial injury. By contrast, CDC42 downregulation aggravated the myocardial injury again. PI3K/AKT pathway was activated by MSC-EV. These findings provide insights into how H19 shuttled by EV mitigates cardiac remodeling through a competitive endogenous RNA network regarding miR-29b-3p and CDC42.

Source apportionment and source-specific risk assessment of bioavailable metals in river sediments of an anthropogenically influenced watershed in China.

Integrated source analysis and risk assessment of metals facilitate the development of targeted risk management strategies. However, previous studies usually addressed total concentration rather than bioavailability, and consequently overestimated metal risk, especially natural source-related risk. In this study, a source-specific risk assessment was conducted by integrating the source analysis of bioavailable metals in surface sediments. Moreover, risk assessment was performed using two bioavailability-based indices: the total availability risk index (TARI) and a modified index of mean probable effect concentration quotients (mPEC-Q). A representative river watershed in eastern China was selected as the study area. Findings revealed that the total concentrations of Pb, Cu, Zn, Cr, and Ni in the sediments were 1.4-2.2 times higher than the local soil background values. Using a modified community bureau of reference (BCR) sequential extraction procedure, the dominant fraction for Pb, Cu, Zn, and Cr in the studied area was found to be the residual fraction, constituting 53.63-62.44% of the total concentrations. This suggested that a significant portion of the metals potentially originated from natural sources. Nevertheless, the concentration enrichment ratio (CER) indicated that anthropogenic sources contributed significantly, accounting for 67.84-87.68% of bioavailable metals. The positive matrix factorization (PMF) model further identified three different sources of bioavailable metals, with a descending concentration contribution sequence of industrial sources (37.61%), mixed traffic and natural sources (33.17%), and agricultural sources (29.22%). Both the TARI and mPEC-Q index values indicated that the bioavailable metals generally posed a moderate risk, and Ni was the priority pollutant. Industrial sources contributed the most to the total risk, although the contribution from TARI-based assessment (37.27%) was lower than that from the mPEC-Q assessment (46.43%). This study provides an example of the consideration of metal bioavailability in the context of source-specific risk assessments to develop more reasonable management strategies.

Telemedicine network latency management system in 5G telesurgery: a feasibility and effectiveness study.

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.

Effects of ulinastatin therapy in deep vein thrombosis prevention after brain tumor surgery: A single-center randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common neurosurgical complication after brain tumor resection, and its prophylaxis has been widely studied. There are no effective drugs in the clinical management of venous thromboembolism, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas. AIM: To explore whether ulinastatin (UTI) can prevent VTE after brain tumor resection. METHODS: The present research included patients who underwent brain tumor resection. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were the incidence of VTE, coagulation function, pulmonary emboli, liver function, renal function, and drug-related adverse effects. RESULTS: A total of 405 patients were evaluated between January 2019 and December 2021, and 361 of these were initially enrolled in the study to form intention-to-treat, which was given UTI (n = 180) or placebo (n = 181) treatment in a random manner. There were no statistically significant differences in baseline clinical data between the two groups. The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group. UTI can improve coagulation dysfunction, pulmonary emboli, liver function, and renal function. No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea, vomiting, hospital stays, or hospitalization costs. The incidence of allergies was higher in the UTI group than in the placebo group. CONCLUSION: The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.

Correlation between physical activity and adolescent idiopathic scoliosis: a systematic review.

BACKGROUND: The multifactorial aetiology of scoliosis is well known. Physical activity is considered both a treatment and causative factor for idiopathic scoliosis; however, evidence for a causal relationship between physical activity levels and idiopathic scoliosis in adolescents is conflicting. Therefore, we aimed to summarise the current evidence regarding the association between adolescent idiopathic scoliosis and physical activity and further to assess whether the relationship is dose dependent. METHODS: PubMed, Cochrane, Scopus, and Web of Science databases were searched from 1991 to July 2022 using the following main keywords: adolescent idiopathic scoliosis, physical activity, and risk factors, supplemented with manual searches, secondary citations, and reference searches. The quality of the included literature was evaluated using the Scale for Reporting Observational Studies in Enhanced Epidemiology guidelines. RESULTS: Eight studies were included in this review, of which six reported an association between adolescent idiopathic scoliosis and physical activity levels and two reported no association. One British study reported reduced physical function early in life as a new risk factor for scoliosis onset. CONCLUSIONS: Physical activity is strongly associated with adolescent idiopathic scoliosis. Physical activity should be encouraged as it plays an important role in the prevention of adolescent idiopathic scoliosis. Further research is needed to determine the dose-dependent relationship between physical activity and prevention of adolescent idiopathic scoliosis.

A prediction model of risk factors of poor wound healing after craniocerebral surgery.

Objective: To explore the independent risk factors of poor wound healing after craniocerebral surgery, and to generate a risk prediction model. Methods: A single-center retrospective observational analysis of 160 patients who underwent craniocerebral surgery in The 904th Hospital of the Joint Logistics Support Force of the PLA from February 2018 to February 2021 was carried out. Patients were divided into Group-A (n=70) and Group-B (n=90) according to postoperative wound healing outcome. Logistic regression was used to analyze the independent risk factors, and a nomogram prediction model was constructed using R software. The receiver operating characteristic (ROC) curve was used to test the predictive ability of the model, and the fitting effect was verified by Hosmer Lemeshow. Results: The duration of operation, surgical site infection, diabetes mellitus, and the time of intubation in Group-B were significantly lower than Group-A (P<0.05). Serum albumin (ALB) and hemoglobin (HGB) in Group-B were significantly higher than those in Group-A (P<0.05). Logistic regression analysis showed that long operation duration, surgical site infection, duration of drainage tube, ALB <35g/L, and abnormal HGB were independent risk factors for poor wound healing (P<0.05). The area under the ROC curve (AUC) predicted by the model was 0.932, 95%CI (0.862~1.000). The Hosmer-Lemeshow goodness of fit test showed that the expected probability calculated by the model matched the actual probability (P>0.05). Conclusions: Long operation duration, surgical site infection, duration of drainage tube, ALB <35g/L, and abnormal HGB were risk factors for poor wound healing. The nomograph model based on these factors showed good discrimination, calibration, and clinical effectiveness in predicting poor wound healing.

New Monoterpene Glycoside Paeoniflorin Derivatives as NO and IL-1ß Inhibitors: Synthesis and Biological Evaluation.

Several monoterpene glycoside compounds were extracted from Paeonia lactiflora Pall. Among them, paeoniflorin, a water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall, exhibits excellent antioxidant pharmacological functions. Initially, Sc(CF3SO3)3 was employed as the catalyst for paeoniflorin's dehydration and rearrangement reactions with alcohols. Subsequently, structural modifications were performed on paeoniflorin through a series of responses, including acetylation, deacetylation, and debenzoylation, ultimately yielding 46 monoterpene glycoside derivatives. The potential inhibitory effects on the pro-inflammatory mediators interleukin-1 beta (IL-1ß) and nitric oxide (NO) were assessed in vitro. The results revealed that compounds 29 and 31 demonstrated notable inhibition of NO production, while eight derivatives (3, 8, 18, 20, 21, 29, 34, and 40) displayed substantial inhibitory effects on the secretion of IL-1ß. Computational research was also undertaken to investigate the binding affinity of the ligands with the target proteins. Interactions between the proteins and substrates were elucidated, and corresponding binding energies were calculated accordingly. The findings of this study could provide valuable insights into the design and development of novel anti-inflammatory agents with enhanced pharmacological properties.

In Situ Toxicity Reduction and Food Safety Assessment of Pak Choi (Brassica campestris L.) in Cadmium-Contaminated Soil by Jointly Using Alkaline Passivators and Organic Fertilizer.

An economical and effective method is still lacking for cadmium (Cd) toxicity reduction and food product safety improvement in soil-vegetable systems. Therefore, this study aimed to reduce the Cd toxicity to pak choi (Brassica campestris L.) by jointly using passivators and organic fertilizer, highlighting food products' safety based on pot experiments. The results showed that compared with the control, organic fertilizer decreased the Cd content in edible parts and the soil's available Cd by 48.4% and 20.9% on average, respectively, due to the 0.15-unit increases in soil pH. Once jointly applied with passivators, the decrements increased by 52.3-72.6% and 32.5-52.6% for the Cd content in edible parts and for the soil's available Cd, respectively, while the pH increment increased by 0.15-0.46 units. Compared with the control, the transport factor of Cd was reduced by 61.9% and 50.9-55.0% when applying organic fertilizer alone and together with the passivators, respectively. The combination treatment of biochar and organic fertilizer performed the best in decreasing the Cd content in the edible parts and the soil's available Cd. The combination treatment of fish bone meal and organic fertilizer induced the greatest increases in soil pH. The grey relational analysis results showed that the combination treatment of biochar and organic fertilizer performed the best in reducing the potential Cd pollution risk, thereby highlighting the vegetable food safety. This study provides a potential economical and effective technology for toxicity reduction and food safety in Cd-polluted soil.

Deep learning techniques for imaging diagnosis of renal cell carcinoma: current and emerging trends.

This study summarizes the latest achievements, challenges, and future research directions in deep learning technologies for the diagnosis of renal cell carcinoma (RCC). This is the first review of deep learning in RCC applications. This review aims to show that deep learning technologies hold great promise in the field of RCC diagnosis, and we look forward to more research results to meet us for the mutual benefit of renal cell carcinoma patients. Medical imaging plays an important role in the early detection of renal cell carcinoma (RCC), as well as in the monitoring and evaluation of RCC during treatment. The most commonly used technologies such as contrast enhanced computed tomography (CECT), ultrasound and magnetic resonance imaging (MRI) are now digitalized, allowing deep learning to be applied to them. Deep learning is one of the fastest growing fields in the direction of medical imaging, with rapidly emerging applications that have changed the traditional medical treatment paradigm. With the help of deep learning-based medical imaging tools, clinicians can diagnose and evaluate renal tumors more accurately and quickly. This paper describes the application of deep learning-based imaging techniques in RCC assessment and provides a comprehensive review.

SIS-Based Electrostatic Spinning High-Safety Lithium-Ion Battery Separators.

As an important component, the properties of separators directly affect the capacity, life, and safety performance of lithium-ion batteries (LIBs). The high thermal stability and safety application value of the thermoplastic elastomer poly(styrene-b-isoprene-b-styrene) block copolymer (SIS) with different block ratios were explored to enhance the thermal stability and mechanical strength of the cross-linked polyacrylonitrile (PAN) membranes by vulcanization cross-linking and heat treatment. Among these membranes, the sample named the S/PAN/SIS-4019 separator was confirmed to be a self-closing separator that can cope with the thermal runaway, attributing to the continued fusion of the SIS soft and hard segments in the cross-linked structure under high-temperature heat treatment. Moreover, the tensile strength of S/PAN/SIS-4019 separator increased to 17.49 MPa, which was better than that of Celgard 2400, PAN, and other inlay separators. Using S/PAN/SIS-4019 as a battery separator, lithium-ion batteries showed a superior electrochemical performance compared to the usage of Celgard 2400. Owing to the stable pore structure and thermally protected self-shutdown mechanism, the overall properties of the obtained cross-linked separator were improved in terms of higher thermal stability, high ionic conductivity, and electrochemical properties.