Immobilization and Catalytic Conversion of Polysulfide by In-Situ Generated Nickel in Hollow Carbon Fibers for High-Rate Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are considered promising energy-storage systems because of their high theoretical energy density, low cost, and eco-friendliness. However, problems such as the shuttle effect can result in the loss of active materials, poor cyclability, and rapid capacity degradation. The utilization of a structural configuration that enhances electrochemical performance via dual adsorption-catalysis strategies can overcome the limitations of Li-S batteries. In this study, an integrated interlayer structure, in which hollow carbon fibers (HCFs) were modified with in-situ-generated Ni nanoparticles, was prepared by scalable one-step carbonization. Highly hierarchically porous HCFs act as the carbon skeleton and provide a continuous three-dimensional conductive network that enhances ion/electron diffusion. Ni nanoparticles with superior anchoring and catalytic abilities can prevent the shuttle effect and increase the conversion rate, thereby promoting the electrochemical performance. This synergistic effect resulted in a high capacity retention of 582 mAh g-1 at 1 C after 100 cycles, providing an excellent rate capability of up to 3 C. The novel structure, wherein Ni nanoparticles are embedded in cotton-tissue-derived HCFs, provides a new avenue for enhancing electrochemical performance at high C rates. This results in a low-cost, sustainable, and high-performance hybrid material for the development of practical Li-S batteries.

Soy protein isolate ameliorate gel properties by regulating the non-covalent interaction between epigallocatechin-3-gallate and myofibrillar protein.

This study primarily investigated the improvement of high-dose Epigallocatechin-3-Gallate (EGCG)-induced deterioration of MP gel by soy protein isolate (SPI) addition. The results showed that EGCG could interact with MP, SPI, and HSPI (heated), indicating the competitive ability of SPI/HSPI against EGCG with MP. EGCG was encapsulated by SPI/HSPI with high encapsulation efficiency and antioxidation, with antioxidant activities of 78.5% âˆ¼ 79.2%. FTIR and molecular docking results revealed that MP, SPI, and HSPI interacted with EGCG through hydrogen bonding and hydrophobic interactions. SPI/HSPI competed with MP for EGCG, leading to the restoration of MHC and Actin bands, alleviating the aggregation caused by EGCG and oxidation. Additionally, SPI/HSPI-E significantly reduced the high cooking loss (23.71 and 26.65%) and gel strength (13.60 and 17.02%) induced by EGCG. Hence, SPI competed with MP for EGCG binding site to ameliorate MP gel properties, thereby alleviating the detrimental changes in MP caused by high-dose EGCG and oxidation.

Electrostatic-Field-Induced Collapse of Nanobubbles in Nanochannels.

The adsorbed nanobubbles inside the nanochannels can cause fluid transport blockages, which will obviously degrade the nanodevice performance and reduce the lifetime. However, due to small-scale effects, the removal of nanobubbles is a huge challenge at the nanoscale. Herein, molecular dynamics simulations are carried out to study the effect of the electrostatic field on underwater nitrogen nanobubbles confined in nanochannels. It is found that the nanobubbles will collapse under an appropriate electrostatic field, thereby unblocking the transport of water in the nanochannels. The formation of ordered water structures induced by electrostatic fields plays an important role in the removal of nanobubbles from the nanochannels. Our findings provide a convenient, controllable, and remote way to address the blockage problem of nanobubbles in nanochannels, which may have potential applications in improving the performance of fuel cells.

[Treatment of hypoxia-induced ED in high-altitude areas by transcutaneous low-frequency electrical stimulation based on the parameters obtained from visualized precision electrophysiological diagnosis].

OBJECTIVE: To investigate the effects of visualized precision electrophysiological diagnosis and transcutaneous low-frequency electrical stimulation (TES) on hypoxia-induced ED in high-altitude areas. METHODS: This study included 152 ED patients from high-altitude hypoxic areas treated by TES based on the parameters obtained from visualized precision electrophysiological diagnosis. We followed up the patients for 1 to 3 months and compared their IIEF-5 scores, nocturnal penile tumescence and rigidity (NPTR) and infrared thermal metabolic technology (TMT)-based temperature of the whole body and diseased parts before and after treatment. RESULTS: All the patients successfully completed 1 to 3 courses of TES. There were no statistically significant differences in the IIEF-5 scores (P<0.05) and penile tip optimal erection rigidity and duration (P<0.01) of the patients before and after treatment. TMT images indicated a temperature change of >1.5 ℃ in the penis and bilateral inguinal regions after treatment, suggesting the effectiveness of electrical stimulation. No recurrence was observed during the follow-up. CONCLUSION: TES based on the parameters obtained from visualized precision electrophysiological diagnosis has a definite effect on hypoxia-induced ED by enhancing oxygen supply to the penile corpus cavernosum and improving its function and structure.

Philadelphia chromosome-like acute lymphoblastic leukemia with concomitant rearrangements of CRLF2 and ABL1: a pediatric case report.

BACKGROUND: BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. CASE PRESENTATION: We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. CONCLUSIONS: Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.

Network Pharmacology and Molecular Docking Integrated with Molecular Dynamics Simulations Investigate the Pharmacological Mechanism of Yinchenhao Decoction in the Treatment of Non-alcoholic Fatty Liver Disease.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health and economic burden globally. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that has been validated to exert therapeutic effects on NAFLD. OBJECT: The current study aimed to explore the pharmacological mechanisms of YCHD on NAFLD and further identify the potential active compounds acting on the main targets. METHODS: Compounds in YCHD were screened and collected from TCMSP and published studies, and their corresponding targets were obtained from the SWISS and SEA databases. NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The "compound- intersection target" network was constructed to recognize the key compounds. Moreover, a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed to enrich the functional information of the intersection targets. Then, molecular docking was used to identify the most promising compounds and targets. Finally, molecular dynamics (MD) simulations were performed to verify the binding affinity of the most potential compounds with the key targets. RESULTS: A total of 53 compounds and 556 corresponding drug targets were collected. Moreover, 2684 NAFLD-related targets were obtained, and 201 intersection targets were identified. Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic process, and regulation of MAP kinase activity, were closely related to the treatment of NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway, and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking showed that quercetin and isorhamnetin were the potential active compounds, while AKT1, IL1B, and PPARG were the most promising targets. MD simulations further verified that the binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49 kcal/mol) was due to their lowest binding free energy. CONCLUSION: This study demonstrated that YCHD exerts therapeutic effects for the treatment of NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological research on the potential mechanisms of YCHD in NAFLD.

A new species of Cincticostella Allen, 1971 (Ephemeroptera, Ephemerellidae) from Yunnan, China and establishment of a new species complex.

Cincticostellajianchuan sp. nov. from Dali Bai Autonomous Prefecture, Yunnan Province, China, is described based on chorionic structure, nymph, and winged stages. The new species is closely related to C.fusca (Kang & Yang, 1995), but it can be distinguished in the male imago stage by its mesonotum and penes morphology, coloration, and the forking point of the stem of MA+Rs on the forewing; in the nymph stage, it can be distinguished by the length of the posterolateral projections of abdominal segment IX and the setation of the abdominal terga. Compared to other congeners, nymphs and male imagoes of the new species and C.fusca share several morphological characteristics, such as a larger body, mesothorax with medially notched anterolateral projections, forefemur without a subapical band of transverse spines of the nymphs, the area between C, Sc and R1 of the forewings distinctly pigmented, and an apical sclerite on the ventral face of the penes of the male imagoes, supporting the proposition of a new species complex, the jianchuan complex. The systematics of Cincticostella and related genera are discussed briefly.

Differential diagnosis value of sympathetic skin response and cutaneous silent period on early-stage multiple system atrophy and Parkinson disease.

PURPOSE: Early differentiation between Parkinson's disease (PD) and Multiple system atrophy (MSA), particularly the parkinsonian subtypes (MSA-P), is challenging due to similar clinical symptoms. We aimed to evaluate Sympathetic skin response (SSR) and Cutaneous silent period (CSP) parameters in patients with MSA-P and PD to identify possible biomarkers that could distinguish the two groups of patients in early stage. METHODS: 22 individuals with early-stage MSA-P, 29 with early-stage PD, and 28 healthy controls were recruited from Guangdong Provincial People's Hospital. Demographic data was collected for all participants. Their SSR and CSP were evaluated using clinical electromyography equipment. Data were compared between different groups. The diagnostic accuracy of SSR and CSP parameters was calculated using the ROC curve. Logistic regression was used to produce an integration model to enhance diagnostic utility. RESULTS: Foot amplitude, CSP end latency and duration distinguished MSA-P from PD with the area under the curve (AUC) 0.770, 0.806, and 0.776, respectively. Foot and hand SSR amplitude distinguished PD from HC with the AUC 0.871 and 0.768, respectively. Foot SSR amplitude, hand SSR amplitude, and CSP end latency distinguished MSA-P from HC with the AUC 0.964, 0.872, and 0.812, respectively. The combination of SSR and CSP parameters differentiation between MSA-P and PD, PD and HC with the AUC 0.829 and 0.879, respectively. CONCLUSIONS: Analysis of SSR and CSP parameters showed excellent diagnostic accuracy in discriminating patients with early-stage MSA-P from HC and good diagnostic accuracy in discriminating patients with MSA-P from PD with early stages.

An Organic Molecular Mimetic Metal-Free Heterogeneous Catalyst for Electrocatalytic Alkyne Semihydrogenation.

The direct construction of metal-free catalysts on conductive substrates for electrocatalytic organic hydrogenation reactions is significant but still unexplored. Here, learning from the homogeneous molecular catalysts, an organic molecular mimetic metal-free heterogeneous catalyst is designed and constructed in situ on a graphite flake electrode via a mild electrochemical oxidation‒reduction relay strategy. The as-prepared -COOH- and -OH-functionalized metal-free catalyst exhibits an electrocatalytic alkyne semihydrogenation performance with a 72% Faradaic efficiency, 99% selectivity and 96% yield of the alkene product, which is comparable to that of noble metal catalysts. The removal of these oxygen-containing groups leads to negligible activity. The experimental and calculation results reveal that the origin of the high activity can be assigned to the -COOH and -OH groups on graphite. A flow electrolytic cell delivers ten grams of hydrogenated products with 81% Faradaic efficiency. This metal-free catalyst is also suitable for gas-phase acetylene semihydrogenation and other electrocatalytic hydrogenation reactions.

Enhancing the Antitumor Efficacy of Oncolytic Adenovirus Through Sonodynamic Therapy-Augmented Virus Replication.

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.

A propensity-score-matched comparison of standard and extended pelvic lymph node dissection in robot-assisted laparoscopic radical cystectomy.

To compare the difference in perioperative outcomes between standard pelvic lymph node dissection (sPLND) and extended pelvic lymph node dissection (ePLND) in robot-assisted radical cystectomy (RARC) and evaluate the survival outcomes. The clinical data were retrospectively collected from patients who underwent RARC between January 2016 and December 2020 in Nanjing Drum Hospital. The patients were divided into sPLND and ePLND group according to the extent of pelvic lymph node dissection. Finally, 80 pairs of patients obtained for two groups by propensity score matching (PSM) and their perioperative and survival outcomes were analyzed. The median number of dissected lymph nodes (LN) after PSM was 13 in sPLND group and 16 in ePLND group (P = 0.004). Perioperative complications were similar between 2 groups. After PSM, ePLND improved 5-year RFS and OS in all patients (85.74 vs. 61.94%, P = 0.004; 82.80 vs. 67.50%, P = 0.033), patients with ≥ T3 disease (73.66 vs. 23.86%; P = 0.007; 68.20 vs. 36.20%; P = 0.032) and patients with LN metastasis (67.70 vs. 7.33%; P = 0.004; 60.60 vs. 16.67%; P = 0.045) compared to sPLND. Extended PLND significantly increased lymph node yield without increasing complication and improved RFS and OS compared to sPLND.

Duplex Fluorinated and Atomic Layer Deposition-Derived ZrO2 Coatings Improve the Corrosion Resistance and Mechanical Properties of Mg-2Zn-0.46Y-0.5Nd (wt.%) Alloy Plates and Screws.

This study investigated the corrosion resistance and mechanical properties of Mg-2Zn-0.46Y-0.5Nd (wt.%) alloy plates and screws with fluorinated coatings and atomic layer deposition (ALD)-derived zirconia (ZrO2) coatings in vitro under physiological stress conditions. Synthetic polyurethane hemimandible replicas were split and fixed as the following three groups of magnesium alloy plates and screws: no additional surface coating treatment (Group A), with fluorinated coatings (Group B), and with duplex fluorinated and ALD-derived 100 nm ZrO2 coatings (Group C). A circulating stress of 1-10 N was applied to the distal bone segment, and a 4-week simulated body fluid immersion test was employed to study the remaining material volume and the mechanical properties of the different groups. Compared with Group A and Group B, the degradation rate of magnesium alloy plates and screws' head regions was significantly slowed down under the protection of duplex MgF2/ZrO2 coatings (p < 0.01). There was no significant difference in the degradation rate of the screw shaft region between groups (p = 0.077). In contrast to fluoride coatings, duplex MgF2/ZrO2 coatings maintained the mechanical strength of magnesium alloy plates and screws after a 14 day in vitro SBF immersion test. We conclude that duplex MgF2/ZrO2 coatings exhibited a certain protective effect on the Mg alloy plates and screws under physiological stress conditions.

Exendin-4, a glucagon-like peptide-1 receptor agonist, alleviates muscular dysfunction and wasting in a streptozotocin-induced diabetic mouse model compared to metformin.

Diabetic muscular atrophy is becoming a fast-growing problem worldwide, including sarcopenia, which is associated with substantial mortality and morbidity risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been marketed and suggested to exert protective effects on not only glycemic control but also diabetic complications in diabetic patients. In this study, we investigated the therapeutic use of GLP-1RAs exendin-4, compared to antidiabetic drug metformin, for the intervention of muscular dysfunction during diabetic conditions using a streptozotocin (STZ)-induced diabetic mouse model. The results showed that both exendin-4 and metformin could effectively alleviate hyperglycemia in diabetic mice, and also counteract diabetes-induced muscle weight loss, weaker grip, and changes in muscle fiber cross-sectional area distribution. Unexpectedly, exendin-4, but not metformin, enhanced the increased kidney weight and histological change in diabetic mice. Taken together, these findings suggest that both exendin-4 and metformin could effectively improve the diabetic hyperglycemia and muscular dysfunction; but exendin-4 may aggravate the nephropathy in STZ-induced diabetic mice.

Gender and age related brain structural and functional alterations in children with autism spectrum disorder.

To explore the effects of age and gender on the brain in children with autism spectrum disorder using magnetic resonance imaging. 185 patients with autism spectrum disorder and 110 typically developing children were enrolled. In terms of gender, boys with autism spectrum disorder had increased gray matter volumes in the insula and superior frontal gyrus and decreased gray matter volumes in the inferior frontal gyrus and thalamus. The brain regions with functional alterations are mainly distributed in the cerebellum, anterior cingulate gyrus, postcentral gyrus, and putamen. Girls with autism spectrum disorder only had increased gray matter volumes in the right cuneus and showed higher amplitude of low-frequency fluctuation in the paracentral lobule, higher regional homogeneity and degree centrality in the calcarine fissure, and greater right frontoparietal network-default mode network connectivity. In terms of age, preschool-aged children with autism spectrum disorder exhibited hypo-connectivity between and within auditory network, somatomotor network, and visual network. School-aged children with autism spectrum disorder showed increased gray matter volumes in the rectus gyrus, superior temporal gyrus, insula, and suboccipital gyrus, as well as increased amplitude of low-frequency fluctuation and regional homogeneity in the calcarine fissure and precentral gyrus and decreased in the cerebellum and anterior cingulate gyrus. The hyper-connectivity between somatomotor network and left frontoparietal network and within visual network was found. It is essential to consider the impact of age and gender on the neurophysiological alterations in autism spectrum disorder children when analyzing changes in brain structure and function.

Human biomonitoring of serum polycyclic aromatic hydrocarbons and oxygenated derivatives by gas chromatography coupled with tandem mass spectrometry.

While polycyclic aromatic hydrocarbons (PAHs) are well-known for their potential carcinogenic and mutagenic effects, the health implications of exposure to oxygenated PAHs (OPAHs), which are significant substitutes with increased persistence and bioaccumulation, are less understood. In this work, we compared the background levels of liquid-liquid, solid-phase, and supported-liquid extraction for the determination of serum PAHs and OPAHs. Liquid-liquid extraction demonstrated minimal background interference and was validated and used for human biomonitoring of PAHs and OPAHs in 240 participants using gas chromatography coupled with tandem mass spectrometry. We observed significant positive correlations between these compounds using Spearman correlation analysis. Furthermore, we investigated the concentration levels and compositions of PAHs and OPAHs among different demographic characteristics, including gender, age, and body mass index. Linear regression analysis demonstrated a weak but significant correlation between total concentrations of PAHs and OPAHs and age and body mass index. A multivariate linear regression analysis was then conducted to examine the association of exposure to individual PAHs and OPAHs with the body mass index. Naphthalene exposure and body mass index showed a statistically significant positive correlation, suggesting that higher levels of naphthalene exposure are associated with higher body mass index values. This study establishes a robust method for biomonitoring PAHs and OPAHs in serum, evaluating the exposure levels of these compounds in healthy adults and highlighting their associations with demographic characteristics.

The structural basis of the activation and inhibition of DSR2 NADase by phage proteins.

DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.

Optimizing processes of care and time to diagnosis in acute aortic dissection patients in a chest pain center by implementing a multidisciplinary cooperative first aid mode - A quality improvement report.

OBJECTIVE: This study aimed to explore the effectiveness of a multidisciplinary cooperative first aid model in the process of establishing a chest pain center specializing in acute aortic dissection (AD). DESIGN: A quality improvement report. METHODS: A total of 142 patients with acute aortic dissection treated before and after the optimization of the chest pain center process in our hospital were included. According to their admission time: the group before the optimization process was designated as the control group (66 cases) and the group after the optimization process was the intervention group (76 cases). The control group received conventional emergency treatment, while the intervention group received treatment through a multidisciplinary cooperative first aid model. The treatment times for both groups were compared: the time from first medical contact(FMC) to completion of an electrocardiogram (ECG), the diagnosis time, and the time spent in the emergency department. RESULTS: The research findings revealed that the intervention group had significantly shorter times for FMC-to-ECG, diagnosis time, and emergency stay compared to the control group (P < 0.001). CONCLUSION: Our findings indicate that by optimizing the multidisciplinary cooperative first aid model and procedures, the treatment of patients has indeed been effectively ensured, achieving safety outcomes. IMPLICATIONS FOR CLINICAL PRACTICE: For chest pain centers, we suggest that to use multidisciplinary cooperative first aid model to get repaid and definite diagnosis of various causes of chest pain. A bedside transthoracic echocardiography is recommended to use in order to identify AD before proceeding with further treatment.

Correlation between hearing loss and mild cognitive impairment in the elderly population: Mendelian randomization and cross-sectional study.

Background: Hearing loss and tinnitus have been linked to mild cognitive impairment (MCI); however, the evidence is constrained by ethical and temporal constraints, and few prospective studies have definitively established causation. This study aims to utilize Mendelian randomization (MR) and cross-sectional studies to validate and analyze this association. Methods: This study employs a two-step approach. Initially, the genetic data of the European population from the Genome-wide association studies (GWAS) database is utilized to establish the causal relationship between hearing loss and cognitive impairment through Mendelian randomization using the inverse variance weighted (IVW) method. This is achieved by identifying strongly correlated single nucleotide polymorphisms (SNPs), eliminating linkage disequilibrium, and excluding weak instrumental variables. In the second step, 363 elderly individuals from 10 communities in Qingdao, China are assessed and examined using methods questionnaire survey and pure tone audiology (PTA). Logistic regression and multiple linear regression were used to analyze the risk factors of MCI in the elderly and to calculate the cutoff values. Results: Mendelian randomization studies have shown that hearing loss is a risk factor for MCI in European populations, with a risk ratio of hearing loss to MCI loss of 1. 23. The findings of this cross-sectional study indicate that age, tinnitus, and hearing loss emerged as significant risk factors for MCI in univariate logistic regression analysis. Furthermore, multivariate logistic regression analysis identified hearing loss and tinnitus as potential risk factors for MCI. Consistent results were observed in multiple linear regression analysis, revealing that hearing loss and age significantly influenced the development of MCI. Additionally, a notable finding was that the likelihood of MCI occurrence increased by 9% when the hearing threshold exceeded 20 decibels. Conclusion: This study provides evidence from genomic and epidemiological investigations indicating that hearing loss may serve as a risk factor for cognitive impairment. While our epidemiological study has found both hearing loss and tinnitus as potential risk factors for cognitive decline, additional research is required to establish a causal relationship, particularly given that tinnitus can manifest as a symptom of various underlying medical conditions.

ß-arrestin2 is indispensable for the antidepressant effects of fluoxetine via inhibiting astrocytic pyroptosis in chronic mild stress mouse model for depression.

ß-arrestin2 is a versatile protein for signaling transduction in brain physiology and pathology. Herein, we investigated the involvement of ß-arrestin2 in pharmacological effects of fluoxetine for depression. A chronic mild stress (CMS) model was established using wild-type (WT) and ß-arrestin2-/- mice. Behavioral results demonstrated that CMS mice showed increased immobility time in the tail suspension test and forced swimming test, elevated concentrations of pro-inflammatory factors in peripheral blood, increased expression of pyroptosis-related proteins, and increased co-labeling of glial fibrillary acidic protein and Caspase1 p10 in the hippocampus compared to the CON group. Treatment with fluoxetine (FLX) ameliorated these conditions. However, compared with the ß-arrestin2-/- CMS group, these results of the ß-arrestin2-/- CMS + FLX group showed no significant changes. These results suggested that the above effects of FLX could be eliminated by knocking out ß-arrestin2. Mass spectrometry implying that FLX promoted the binding of ß-arrestin2 to the NLRP2 inflammasome of depressed mice. Subsequently, the results of the cellular experiments suggested that the 5HT2B receptor antagonist may attenuate L-kynurenine + ATP-induced cell pyroptosis by attenuating NLRP2 binding to ß-arrestin2. We further found that the lack of ß-arrestin2 eliminated the anti-pyroptosis effect of fluoxetine. In conclusion, ß-arrestin2 is an essential protein for fluoxetine to alleviate pyroptosis in the hippocampal astrocytes of CMS mice. Mechanistically, we found that the 5-HT2BR-ß-arrestin2-NLRP2 axis is vital for maintaining the antidepressant effects of fluoxetine.

Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances.

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.