Investigation into enhanced performance of toluene and Hg0 stimulative abatement over Cr-Mn oxides co-modified columnar activated coke.

In this study, a string of Cr-Mn co-modified activated coke catalysts (XCryMn1-y/AC) were prepared to investigate toluene and Hg0 removal performance. Multifarious characterizations including XRD, TEM, SEM, in situ DRIFTS, BET, XPS and H2-TPR showed that 4%Cr0.5Mn0.5/AC had excellent physicochemical properties and exhibited the best toluene and Hg0 removal efficiency at 200℃. By varying the experimental gas components and conditions, it was found that too large weight hourly space velocity would reduce the removal efficiency of toluene and Hg0. Although O2 promoted the abatement of toluene and Hg0, the inhibitory role of H2O and SO2 offset the promoting effect of O2 to some extent. Toluene significantly inhibited Hg0 removal, resulting from that toluene was present at concentrations orders of magnitude greater than mercury's or the catalyst was more prone to adsorb toluene, while Hg0 almost exerted non-existent influence on toluene elimination. The mechanistic analysis showed that the forms of toluene and Hg0 removal included both adsorption and oxidation, where the high-valent metal cations and oxygen vacancy clusters promoted the redox cycle of Cr3+ + Mn3+/Mn4+ ↔ Cr6+ + Mn2+, which facilitated the conversion and replenishment of reactive oxygen species in the oxidation process, and even the CrMn1.5O4 spinel structure could provide a larger catalytic interface, thus enhancing the adsorption/oxidation of toluene and Hg0. Therefore, its excellent physicochemical properties make it a cost-effective potential industrial catalyst with outstanding synergistic toluene and Hg0 removal performance and preeminent resistance to H2O and SO2.

Apoptosis and cuproptosis Co-activated Copper-based metal-organic frameworks for cancer therapy.

Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a significant global health challenge, with limited therapeutic options for patients with KRAS-mutated tumors. Herein, a copper-based metal-organic framework (Cu-MOF) was applied as a novel cuproptosis-mediated nanoplatform for lung cancer therapy. Cu-MOF would disassemble and liberate copper ions under the acidic microenvironment of lysosomes of cancer cells, initiating a cascade of cellular events. The released copper ions catalyzes the Fenton reaction, generating hydroxyl radicals that induce oxidative damage, leading to cytoskeletal disruption and activation of caspase-3, ultimately triggering apoptosis. Simultaneously, with the mediation of the key regulatory factor FDX1, we found that the copper ions binding to the mitochondrial protein DLAT could result in the loss of iron-sulfur cluster proteins and aggregation of lipoylated proteins, which culminated in proteotoxic stress-induced cuproptosis. The pronounced anti-tumor effects of Cu-MOF with apoptosis and cuproptosis were confirmed both in vitro and in vivo experiments. Such dual induction of apoptosis and cuproptosis by Cu-MOF presents a promising therapeutic strategy for NSCLC, particularly for KRAS-mutated tumors, and expands potential applications of Cu-based nanomateirals for other cancers.

A systematic review and meta-analysis:comparing the efficacy of the Ilizarov technique alone with lengthening over a nail for lower extremity bone defects.

PURPOSE: The task faced by surgeons becomes significantly more challenging when they encounter lower extremity bone defects due to a variety of causes requiring lengthening. The most discussed and successful approach is the Illizarov technique, or lengthening over a nail (LON):distraction osteogenesis is also widely performed with monoliteral external fixators and intramedullarylengthening nails have increasingly been used in the last decade. METHODS: The data were collected from PubMed, Cochrane Library, Embase, and the Web of Science for all available studies comparing the outcomes of Ilizarov technique alone and LON technique (from January 1, 1997, to November 30, 2023). The outcomes of interest encompassed the external fixation index (EFI) (month/cm), mean duration of follow-up (MFT) (month), length gained (LG) (cm), consolidation index (CIx) (month/cm), and bone healing index (BHI) (month/cm).Complications include pin tract infection rate (PTI), axial deviation rate (AD), occurrence of intramedullary infection (II), delayed consolidation rate (DC), as well as data categorized into three levels of problems, obstacles, and sequelae based on the severity of complications.Two reviewers independently assessed each study for quality and extracted data. The case-control or respective cohort studies were evaluated using the Newcastle-Ottawa scale (NOS) to determine their techniqueological rigor.The Cochrane Collaboration's risk assessment tool was employed to perform quality evaluations for randomized controlled trials. RESULTS: This review included thirteen studies comprising a total of 629 patients.The external fixation index (month/cm) was significantly smaller in the LON technique compared to the Ilizarov technique alone [Mean Difference(MD) = -29.59, 95% CI -39.68--19.49, P < 0.00001].In terms of the mean follow-up time(month) (MD = -0.92, 95% CI -3.49-1.65, P = 0.57), length gained (cm) (MD = -0.87, 95%CI -2.80-1.07, P = 0.38), consolidation index (month/cm) (MD = 0.66, 95% CI -3.44-4.77, P = 0.75), and bone healing index (month/cm) (MD = -3.33, 95% CI -13.07-6.41, P = 0.5), there were no significant differences observed. The LON technique exhibited a lower incidence of axial deviation [Odds Ratio(OR) = 0.06, 95%CI 0.03-0.16, P < 0.00001] and pin tract infection (OR = 0.30, 95%CI 0.18-0.50, P < 0.00001) compared to the Ilizarov technique alone.The remaining complications, such as intramedullary infection rate (OR = 0.93, 95%CI 0.42-2.06, P = 0.85) and delayed consolidation rate(OR = 0.61, 95%CI 0.20-1.86, P = 0.38), did not exhibit statistically significant differences.Our findings demonstrated that the LON technique results in lower incidences of problems (38.5%vs.58.6%) and sequelae (16.6% vs.30.9%) when compared to the Ilizarov technique alone. However, the rates of obstacles (32.4% vs.32.3%) were comparable between the two methods. CONCLUSIONS: Our findings indicate that patients treated with the LON technique experienced significantly shorter external fixation durations and a lower incidence of complications (e.g., pin tract infections and axial deviation) compared to those treated with the Ilizarov technique alone. Other outcome metrics showed no significant differences between the two techniques. However, the LON technique offers substantial benefits, including reduced external fixation times and increased comfort, which enhance patient compliance. In conclusion, the LON technique is a safe, reliable, and effective method for treating tibial and femoral defects.

Distributed Drive Electric Vehicle Handling Stability Coordination Control Framework Based on Adaptive Model Predictive Control.

Distributed drive electric vehicles improve steering response and enhance overall vehicle stability by independently controlling each motor. This paper introduces a control framework based on Adaptive Model Predictive Control (AMPC) for coordinating handling stability, consisting of three layers: the dynamic supervision layer, online optimization layer, and low-level control layer. The dynamic supervision layer considers the yaw rate and maneuverability limits when establishing the ß-ß˙ phase plane stability boundary and designs variable weight factors based on this stability boundary. The online optimization layer constructs the target weight-adaptive AMPC strategy, which can adjust the control weights for maneuverability and lateral stability in real time based on the variable weight factors provided by the dynamic supervision layer. The low-level control layer precisely allocates the driver's requested driving force and additional yaw moment by using torque distribution error and tire utilization as the cost function. Finally, experiments are conducted on a Simulink-CarSim co-simulation platform to assess the performance of AMPC. Simulation results show that, compared to the traditional MPC strategy, this control strategy not only enhances maneuverability under normal conditions but also improves lateral stability control under extreme conditions.

A cuproptosis-related lncRNAs signature predicts prognosis and reveals pivotal interactions between immune cells in colon cancer.

Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA-cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan-Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5-ACKR1, CCL2-ACKR1, and CCL5-CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

Correlation of spinal cord compression angle and increased signal intensity on MRI in patients with ossification of posterior longitudinal ligament.

We retrospectively investigated the correlation between the spinal cord compression angle and increased signal intensity (ISI) in 118 patients with ossification of the posterior longitudinal ligament (OPLL). Patients were analyzed based on the presence and shape of ISI on magnetic resonance imaging. Various indicators, including the spinal cord compression angle, were measured through imaging examinations. Spearman's correlation and logistic regression were used for analyses. Significant positive correlations were observed between the ISI grade and the spinal cord compression angle, maximum spinal canal occupying rate, cervical range of motion, and segmental range of motion. The spinal cord compression ratio and Japanese Orthopaedic Association (JOA) score were negatively correlated with the ISI grade. Regression analysis revealed that the spinal cord compression angle and JOA scores were independent factors that significantly influenced ISI grade. The odds ratio of ISI was 3.858 (95% confidence interval: 0.974-15.278) when comparing the highest and lowest quartiles of the spinal cord compression angle. Patients with a spinal cord compression angle > 35° had more severe imaging manifestations. Thus, a spinal cord compression angle > 35° could serve as a significant indicator of OPLL severity, and greater attention should be focused on treating patients with larger spinal cord compression angles.

Salidroside derivative SHPL-49 attenuates glutamate excitotoxicity in acute ischemic stroke via promoting NR2A-CAMKâ ¡α-Akt /CREB pathway.

BACKGROUND: Ischemic stroke is a significant cause of death and disability with a limited treatment time window. The reduction of early glutamate excitotoxicity using neuroprotective agents targeting N-methyl-d-aspartic acid (NMDA) receptors have attracted recent research attention. SHPL-49, a structurally modified derivative of salidroside, was synthesized by our team. Previous studies have confirmed the neuroprotective efficacy of SHPL-49 in rats with ischemic stroke. However, the underlying mechanisms need to be clarified. METHODS: We conducted in vivo experiments using the permanent middle cerebral artery occlusion rat model to investigate the role of SHPL-49 in glutamate release at different time points and treatment durations. Glutamate transporters and receptor proteins and neural survival proteins in the brain were also examined at the same time points. In vitro, primary neurons and the coculture system of primary neurons-astrocytes were subjected to oxygen-glucose deprivation and glutamate injury. Proteomics and parallel reaction monitoring analyses were performed to identify potential therapeutic targets of SHPL-49, which were further confirmed through in vitro experiments on the inhibition and mutation of the target. RESULTS: SHPL-49 significantly reduced glutamate release caused by hypoxia-ischemia. One therapeutic pathway of SHPL-49 was promoting the expression of glutamate transporter-1 to increase glutamate reuptake and further reduce the occurrence of subsequent neurotoxicity. In addition, we explored the therapeutic targets of SHPL-49 and its regulatory effects on glutamate receptors for the first time. SHPL-49 enhanced neuroprotection by activating the NMDA subunit NR2A, which upregulated the cyclic-AMP response binding protein (CREB) neural survival pathway and Akt phosphorylation. Since calcium/calmodulin-dependent kinase IIα (CaMKIIα) is necessary for synaptic transmission of NMDA receptors, we explored the interaction between CaMKIIα and SHPL-49, which protected CaMKIIα from hypoxia-ischemia-induced autophosphorylation damage. CONCLUSION: Overall, SHPL-49 enhanced neuronal survival and attenuated acute ischemic stroke by promoting the NR2A-CAMKⅡα-Akt/CREB pathway. Our study provides the first evidence demonstrating that the neuroprotective effect of SHPL-49 is achieved by promoting the NR2A subunit to extend the treatment time window, making it a promising drug for ischemic stroke.

An Integrated Approach Using Network Pharmacology and Experimental Validation to Reveal the Therapeutic Mechanism of Weifuchun in Treating Gastric Cancer.

Gastric cancer (GC) is a prevalent malignancy affecting the gastrointestinal tract. Weifuchun (WFC), a Chinese herbal prescription comprising red ginseng, Isodon amethystoides, and Fructus aurantii, is widely used in China for various chronic stomach disorders. However, its therapeutic role and mechanisms in treating GC remain unexplored. In a randomized, controlled, single-blind trial involving postoperative stages II and III GC patients, we compared adjuvant chemotherapy plus WFC (chemo plus WFC group) to adjuvant chemotherapy alone (chemo group) over 6 months. We assessed recurrence and metastasis rates and used systematic pharmacology to predict WFC's active components, screen target genes, and construct network interaction maps, were validated through in vitro experiments. The combined therapy significantly reduced 2-year recurrence and metastasis rates. We identified 67 active ingredients, 211 drug target proteins, 1539 disease targets, 105 shared targets, and 188 signaling pathways associated with WFC. WFC impacted cell apoptosis, proliferation, and the inflammatory response, with top tumor-related signaling pathways involving 5'-adenosine monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinase, nuclear factor kappa-B (NFKB), and apoptosis. In vitro, WFC inhibited proliferation and migration while inducing apoptosis in GC cells, reduced VEGFA, TNFa, and IL6 expressions. Immunocytochemistry showed increased p-AMPK staining, and molecular analysis revealed decreased NFKB and phosphorylation of extracellular-regulated protein kinase 1/2 (ERK1/2) levels, increased p-AMPK and BAX protein levels in WFC-treated cells, effects reversed by Compound C. WFC's antitumor effects involve AMPK-dependent ERK1/2 and NFKB pathways, regulating proliferation, migration, and apoptosis in GC cells.

Design and decoration of copper nanoparticles into lignosulfonate-starch bionanocomposite: Characterization and evaluation of its therapeutic properties on burn wound.

In this report, eco-friendly synthesis for the production of copper nanoparticles by employing the sodium lignosulfonate (NaLS) mixed starch composite (NaLS-Starch/Cu NPs). NaLS-Starch mixed hydrogel has notable reducing and stabilizing potential for preparation of Cu nanoparticles. Characterization of NaLS-Starch/Cu NPs bionanocomposite was subjected to analysis of spectroscopic and microscopic techniques, including FE-SEM, TEM, EDS-elemental mapping, particle size distribution, XRD and ICP. TEM images displayed the spherical structured NaLS-Starch/Cu NPs, averaging 5-10 nm size. NaLS-Starch/Cu NPs were applied to cure the induced burn wounds in 60 Wistar rats. A group was considered as control group. The animals were treated with basal, tetracycline 3 % and NaLS-Starch/Cu NPs 3 % for 30 days and the treatment efficacy was determined according to the burn wound area reduction and molecular and histological characteristics. Taken together, these results support therapeutic use of NaLS-Starch/Cu NPs as potent ointment that may be proposed for burn wound healing. NaLS-Starch/Cu NPs ointment increased the levels of platelet-derived growth factors (PDGF) and fibroblast growth factor (bFGF). The mean wound surface, in all groups treated by NaLS-Starch/Cu NPs was larger than control group.

Mechanism and origin of enantioselectivity for organocatalyzed asymmetric heteroannulation of alkynes in the construction of axially chiral C2-arylquinoline.

Axially chiral C2-arylquinoline has been successfully constructed via asymmetric heteroannulation of alkynes catalyzed by chiral phosphoric acid with high yield and high enantioselectivity. Inspired by this intriguing work, theoretical calculations have been carried out, and the detailed reaction mechanism has been elaborated, in which the whole reaction can be divided into steps including hydrogen transfer, C-N bonding, annulation reaction and the final dehydration processes. The initial hydrogen-transfer reaction has two possible pathways, while the subsequent C-N bonding process has eight possible pathways. Then, after the annulation reaction and the final dehydration processes, the major product and byproduct were formed. QTAIM and IGMH analyses were used to illustrate the role of weak intermolecular interactions in the catalytic process, and the distortion/interaction and EDA analyses provided a deeper understanding of the origin of enantioselectivity. The calculated results are consistent with the experimental results. This work would provide valuable insights into asymmetric reactions catalyzed by chiral phosphoric acid.

Data-independent acquisition in metaproteomics.

INTRODUCTION: Metaproteomics offers insights into the function of complex microbial communities, while it is also capable of revealing microbe-microbe and host-microbe interactions. Data-independent acquisition (DIA) mass spectrometry is an emerging technology, which holds great potential to achieve deep and accurate metaproteomics with higher reproducibility yet still facing a series of challenges due to the inherent complexity of metaproteomics and DIA data. AREAS COVERED: This review offers an overview of the DIA metaproteomics approaches, covering aspects such as database construction, search strategy, and data analysis tools. Several cases of current DIA metaproteomics studies are presented to illustrate the procedures. Important ongoing challenges are also highlighted. Future perspectives of DIA methods for metaproteomics analysis are further discussed. Cited references are searched through and collected from Google Scholar and PubMed. EXPERT OPINION: Considering the inherent complexity of DIA metaproteomics data, data analysis strategies specifically designed for interpretation are imperative. From this point of view, we anticipate that deep learning methods and de novo sequencing methods will become more prevalent in the future, potentially improving protein coverage in metaproteomics. Moreover, the advancement of metaproteomics also depends on the development of sample preparation methods, data analysis strategies, etc. These factors are key to unlocking the full potential of metaproteomics.

Predicting complication risks after sleeve lobectomy for non-small cell lung cancer.

Background: Sleeve lobectomy is a challenging procedure with a high risk of postoperative complications. To facilitate surgical decision-making and optimize perioperative treatment, we developed risk stratification models to quantify the probability of postoperative complications after sleeve lobectomy. Methods: We retrospectively analyzed the clinical features of 691 non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy between July 2016 and December 2019. Logistic regression models were trained and validated in the cohort to predict overall complications, major complications, and specific minor complications. The impact of specific complications in prognostic stratification was explored via the Kaplan-Meier method. Results: Of 691 included patients, 232 (33.5%) developed complications, including 35 (5.1%) and 197 (28.5%) patients with major and minor complications, respectively. The models showed robust discrimination, yielding an area under the receiver operating characteristic (ROC) curve (AUC) of 0.853 [95% confidence interval (CI): 0.705-0.885] for predicting overall postoperative complication risk and 0.751 (95% CI: 0.727-0.762) specifically for major complication risks. Models predicting minor complications also achieved good performance, with AUCs ranging from 0.78 to 0.89. Survival analyses revealed a significant association between postoperative complications and poor prognosis. Conclusions: Risk stratification models could accurately predict the probability and severity of complications in NSCLC patients following sleeve lobectomy, which may inform clinical decision-making for future patients.

From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Genetic Dissection of Major Rice QTLs for Strong Culms and Fine Mapping of qWS5 for Breeding Application in Transplanted System.

BACKGROUND: Rice is one of the major staples that feeds about one half of the global populations, and it is important to identify the genetic loci for the traits related to yield improvement. Lodging will cause severe yield loss when it happens, and stem diameter has been characterized as an important trait for lodging resistance. However, most QTLs for stem diameter have not been finely dissected due to their sensitivity to environmental fluctuation. RESULT: In this study, we performed QTL analysis for stem diameter using populations derived from Nipponbare (NIP) and strong culm variety YYP1, and confirmed the single and combined effect of three major QTLs by recombinant inbred lines (RILs). Based on the QTL location, we found that qWS5 is a novel QTL not well characterized before. To finely dissect the novel locus, several recombinant heterogeneous inbred families (HIFs) were selected from the RILs for linkage analysis and their derived nearly isogenic lines (NILs) were subjected to detailed trait investigation throughout different years. The HIF-NILs strategy confined the QTL to about 380 kb region supported by repeated genotype and phenotype data, and it lays the foundation for QTL cloning in the future. In addition, introgression of the QTL to an elite japonica variety SD785 was performed by successive backcrossing, and it confirmed the value of qWS5 in increasing stem diameter and other agronomic traits during rice breeding. CONCLUSIONS: We prove that qWS5 is a novel QTL with relatively stable effect for stem diameter and the QTL can be finely mapped to small region by the HIF-NILs strategy. The result will facilitate the improvement of rice lodging resistance by molecular marker assisted selection breeding.

Role of TRPC6 in apoptosis of skeletal muscle ischemia/reperfusion injury.

BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.

Spatio-Temporal Joint Optimization-Based Trajectory Planning Method for Autonomous Vehicles in Complex Urban Environments.

Providing safe, smooth, and efficient trajectories for autonomous vehicles has long been a question of great interest in the field of autopiloting. In dynamic and ever-changing urban environments, safe and efficient trajectory planning is fundamental to achieving autonomous driving. Nevertheless, the complexity of environments with multiple constraints poses challenges for trajectory planning. It is possible that behavior planners may not successfully obtain collision-free trajectories in complex urban environments. Herein, this paper introduces spatio-temporal joint optimization-based trajectory planning (SJOTP) with multi-constraints for complex urban environments. The behavior planner generates initial trajectory clusters based on the current state of the vehicle, and a topology-guided hybrid A* algorithm applied to an inflated map is utilized to address the risk of collisions between the initial trajectories and static obstacles. Taking into consideration obstacles, road surface adhesion coefficients, and vehicle dynamics constraints, multi-constraint multi-objective coordinated trajectory planning is conducted, using both differential-flatness vehicle models and point-mass vehicle models. Taking into consideration longitudinal and lateral coupling in trajectory optimization, a spatio-temporal joint optimization solver is used to obtain the optimal trajectory. The simulation verification was conducted on a multi-agent simulation platform. The results demonstrate that this methodology can obtain optimal trajectories safely and efficiently in complex urban environments.

Glioma-Stem-Cell-Derived Exosomes Remodeled Glioma-Associated Macrophage via NEAT1/miR-125a/STAT3 Pathway.

Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma.

Memantine alleviates cognitive impairment and hippocampal morphology injury in a mouse model of chronic alcohol exposure.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.

Surgical resection due to poor outcome of the immunotherapy of a relapsed mediastinal liposarcoma: a case report.

The feasibility of surgery after immunotherapy for mediastinal liposarcoma remains uncertain. Besides, the case of immunotherapy for liposarcoma is still lacking. We report a case of recurrence after resection of a left mediastinal liposarcoma. After recurrence, one course of pembrolizumab plus anlotinib hydrochloride showed no tumor shrinkage, and genetic testing showed CDK4 amplification and PD-L1 TPS <1%; therefore, the plan was changed to one course of pembrolizumab plus palbociclib, but the tumor still did not shrink. Thus, second tumor resection was performed. In addition, the postoperative pathology was still well-differentiated liposarcoma. The significance of immunotherapy in liposarcoma still needs to be further explored. In the absence of surgical contraindications, secondary surgery might be feasible.