CLCuMuV subverts the processing of hydroxyproline-rich systemin to suppress tobacco defenses against insect vectors.

The interactions of insect vector-virus-plant have important ecological and evolutionary implications. The constant struggle of plants against viruses and insect vectors has driven the evolution of multiple defense strategies in the host as well as counter-defense strategies in the viruses and insect vectors. Cotton leaf curl Multan virus (CLCuMuV) is a major causal agent of cotton leaf curl disease in Asia and is exclusively transmitted by the whitefly Bemisia tabaci. Here, we report that plants infected with CLCuMuV and its betasatellite, cotton leaf curl Multan betasatellite (CLCuMuB) enhance the performance of B. tabaci vector, and ßC1 encoded by CLCuMuB plays an important role in begomovirus-whitefly-tobacco tripartite interactions. We showed that CLCuMuB ßC1 suppresses the jasmonic acid signaling pathway by interacting with the subtilisin-like protease 1.7 (NtSBT1.7) protein, thereby enhancing whitefly performance on tobacco plants. Further studies revealed that in the wild type plants, NtSBT1.7 could process tobacco preprohydroxyproline-rich systemin B (NtpreproHypSysB). After CLCuMuB infection, CLCuMuB ßC1 could interfere with the processing of NtpreproHypSysB by NtSBT1.7, thereby impairing plant defenses against whitefly. These results contribute to our understanding of the tripartite interactions among virus, plant, and whitefly, thus offering ecological insights into the spread of vector insect populations and the prevalence of viral diseases.

Viral strategies to antagonize the host antiviral innate immunity: an indispensable research direction for emerging virus-host interactions.

The public's health is gravely at risk due to the current global outbreak of emerging viruses, specifically SARS-CoV-2 and MPXV. Recent studies have shown that SARS-CoV-2 mutants (such as Omicron) exhibit a higher capability to antagonize the host innate immunity, increasing their human adaptability and transmissibility. Furthermore, current studies on the strategies for MPXV to antagonize the host innate immunity are still in the initial stages. These multiple threats from emerging viruses make it urgent to study emerging virus-host interactions, especially the viral antagonism of host antiviral innate immunity. Given this, we selected several representative viruses that significantly threatened human public health and interpreted the multiple strategies for these viruses to antagonize the host antiviral innate immunity, hoping to provide ideas for molecular mechanism research that emerging viruses antagonize the host antiviral innate immunity and accelerate the research progress. The IAV, SARS-CoV-2, SARS-CoV, MERS-CoV, EBOV, DENV, ZIKV, and HIV are some of the typical viruses. Studies have shown that viruses could antagonize the host antiviral innate immunity by directly or indirectly blocking antiviral innate immune signaling pathways. Proviral host factors, host restriction factors, and ncRNAs (microRNAs, lncRNAs, circRNAs, and vtRNAs) are essential in indirectly blocking antiviral innate immune signaling pathways. Furthermore, via controlling apoptosis, ER stress, stress granule formation, and metabolic pathways, viruses may antagonize it. These regulatory mechanisms include transcriptional regulation, post-translational regulation, preventing complex formation, impeding nuclear translocation, cleavage, degradation, and epigenetic regulation.

Curcumin protects against cadmium-induced germ cell death in the testis of rats.

Introduction: Cadmium (Cd) has been shown to disrupt the reproductive system. In this study, we evaluated the protective effects of Curcumin (Cur) against Cd-induced reproductive toxicity. Methods: Exploring the role of Cur in Cd-treated rat models. Results: The study demonstrated that Cd treatment impaired the seminiferous epithelium, leading to increased apoptosis of germ cells. Interestingly, pretreatment with Cur ameliorated the histological damage and decreased the germ cell apoptosis induced by Cd. Furthermore, after Cd exposure, B-cell lymphoma-2 expression was significantly decreased while Bax expression was increased. Pretreatment of rats with Cur protected against germ cell apoptosis by improving the expression of B-cell lymphoma-2 and reducing Bax. Additionally, Cd treatment increased reactive oxygen species, resulting in a decrease in antioxidant enzymes. However, pretreatment of rats with Cur followed by Cd administration led to a substantial decrease in reactive oxygen species levels and increased activities of antioxidant enzymes. Ultrastructural investigations revealed that damage to the mitochondrial structure was significantly ameliorated by Cur pretreatment in Cd-treated rats. Notably, Cur significantly activated the peroxisome proliferator-activated receptor gamma coactivator 1a/Sirtuins-3 signaling pathway. Conclusions: Overall, our data suggest that Cd induces germ cell apoptosis through mitochondrial-induced oxidative stress, but Cur pretreatment offers strong protection against Cd-induced reproductive toxicity.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Overcoming oxygen inhibition in UV photolithography for the fabrication of low-loss polymer waveguides.

Perfluorinated acrylate polymer materials exhibit low absorption loss at 1310 and 1550 nm, but molecular oxygen inhibits their photocuring. We propose a novel, to our knowledge, UV photolithography method incorporating a pre-exposure process for fabricating low-loss perfluorinated acrylate polymer waveguides. During the pre-exposure process, a partially cured thin layer forms on the core layer, effectively overcoming oxygen inhibition in subsequent lithography. Furthermore, the functional group contents of the polymerized materials were characterized by a Raman spectrometer to analyze the development reaction under the pre-exposure layer. Utilizing this improved method, we fabricated a straight waveguide with a length of 21 cm. The experiments showed that the propagation losses are 0.14 dB/cm at 1310 nm and 0.51 dB/cm at 1550 nm. The inter-channel cross talk for a core pitch of 250 µm was measured as low as -49 dB at 1310 nm. Error-free NRZ data transmission over this waveguide at 25 Gb/s was achieved, showcasing the potential in optical interconnect and communication applications.

Genome-wide analysis of bZIP transcription factors and their expression patterns in response to methyl jasmonate and low-temperature stresses in Platycodon grandiflorus.

Background: Platycodon grandiflorus belongs to the genus Platycodon and has many pharmacological effects, such as expectorant, antitussive, and anti-tumor properties. Among transcription factor families peculiar to eukaryotes, the basic leucine zipper (bZIP) family is one of the most important, which exists widely in plants and participates in many biological processes, such as plant growth, development, and stress responses. However, genomic analysis of the bZIP gene family and related stress response genes has not yet been reported in P. grandiflorus. Methods: P. grandiflorus bZIP (PgbZIP) genes were first identified here, and the phylogenetic relationships and conserved motifs in the PgbZIPs were also performed. Meanwhile, gene structures, conserved domains, and the possible protein subcellular localizations of these PgbZIPs were characterized. Most importantly, the cis-regulatory elements and expression patterns of selected genes exposed to two different stresses were analyzed to provide further information on PgbZIPs potential biological roles in P. grandiflorus upon exposure to environmental stresses. Conclusions: Forty-six PgbZIPs were identified in P. grandiflorus and divided into nine groups, as displayed in the phylogenetic tree. The results of the chromosomal location and the collinearity analysis showed that forty-six PgbZIP genes were distributed on eight chromosomes, with one tandem duplication event and eleven segmental duplication events identified. Most PgbZIPs in the same phylogenetic group have similar conserved motifs, domains, and gene structures. There are cis-regulatory elements related to the methyl jasmonate (MeJA) response, low-temperature response, abscisic acid response, auxin response, and gibberellin response. Ten PgbZIP genes were selected to study their expression patterns upon exposure to low-temperature and MeJA treatments, and all ten genes responded to these stresses. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that the expression levels of most PgbZIPs decreased significantly within 6 h and then gradually increased to normal or above normal levels over the 90 h following MeJA treatment. The expression levels of all PgbZIPs were significantly reduced after 3 h of the low-temperature treatment. These results reveal the characteristics of the PgbZIP family genes and provide valuable information for improving P. grandiflorus's ability to cope with environmental stresses during growth and development.

Molecular Mechanism of Yangshen Maidong Decoction in the Treatment of Chronic Heart Failure based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Chronic heart failure (CHF) is a complex multifactorial clinical syndrome leading to abnormal cardiac structure and function. The severe form of this ailment is characterized by high disability, high mortality, and morbidity. Worldwide, 2-17% of patients die at first admission, of which 17-45% die within 1 year of admission and >50% within 5 years. Yangshen Maidong Decoction (YSMDD) is frequently used to treat the deficiency and pain of the heart. The specific mechanism of action of YSMDD in treating CHF, however, remains unclear. Therefore, a network pharmacology-based strategy combined with molecular docking and molecular dynamics simulations was employed to investigate the potential molecular mechanism of YSMDD against CHF. The effective components and their targets of YSMDD and related targets of CHF were predicted and screened based on the public database. The network pharmacology was used to explore the potential targets and possible pathways that involved in YSMDD treated CHF. Molecular docking and molecular dynamics simulations were performed to elucidate the binding affinity between the YSMDD and CHF targets. Screen results, 10 main active ingredients, and 6 key targets were acquired through network pharmacology analysis. Pathway enrichment analysis showed that intersectional targets associated pathways were enriched in the Prostate cancer pathway, Hepatitis B pathway, and C-type lectin receptor signaling pathways. Molecular docking and molecular dynamics simulations analysis suggested 5 critical active ingredients have high binding affinity to the 5 key targets. This research shows the multiple active components and molecular mechanisms of YSMDD in the treatment of CHF and offers resources and suggestions for future studies.

Breviscapine ameliorates autophagy by activating the JAK2/STAT5/BCL2 pathway in a transient cerebral ischemia rat model.

Breviscapine (Bre), an extract from Erigeron breviscapus, has been widely used to treat cerebral ischemia but the mechanisms of its neuroprotective effects need to be clarified. The present study investigated whether Bre could alleviate excessive autophagy induced by cerebral ischemia in the rat middle cerebral artery occlusion (MCAO) ischemia model via activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5)/B-cell lymphoma 2 (BCL2) pathway. Rats were randomly divided into 5 groups, i.e. Sham group, MCAO+saline group, MCAO+Bre group, MCAO+DMSO (Dimethyl sulfoxide) group, and MCAO+Bre+AG490 (Tyrphostin AG490, the inhibitor of STAT5) group. The model was established and neuroprotection was evaluated by determining infarct volumes and conducting neurological behavioral tests. Autophagy levels in the infarct penumbra were detected using transmission electron microscopy and Western blotting. The expression of proteins in the JAK2/STAT5/BCL2 pathway was tested by Western blotting. Compared to the MCAO+saline group, the infarct volumes in the MCAO+Bre group were significantly reduced and neurological behavior improved. Breviscapine administration also significantly increased p-JAK2, p-STAT5, and BCL2 expression but decreased autolysosome numbers; it also downregulated Beclin-1 expression and the LC3II/LCI ratio. The JAK2 inhibitor AG490 reversed these effects. These findings indicate that breviscapine can improve neural recovery following ischemia through alleviating excessive autophagy and activation of the JAK2/STAT5/BCL2 axis.

Clinical evaluation of continuous irrigation with Bikerui combined with negative pressure closed drainage and platelet-rich plasma technique for treatment of stage III-IV pressure ulcer.

Introduction: As a catastrophic complication of bedridden and elderly patients, pressure ulcer usually continuously affects patients' health and quality of life, so the daily care of wounds is attached great importance in clinic. Aim: This work investigated the effect of Bikerui disinfectant + vacuum sealing drainage (VSD) + platelet-rich plasma (PRP) therapy on patients with stage III ~ IV pressure sore. Material and methods: In this work, 110 patients with pressure ulcer (PU) treated in our hospital were enrolled and were randomly divided into an experimental group (Exp group) and a control group (Ctrl group) by a blind selection method, with 55 cases in each group. Patients in the Ctrl group received surgical debridement + VSD for treatment, while those in the Exp group were treated with Bikerui disinfectant + VSD + PRP. Inflammatory response (IR) score, PU healing (PUH) score, healing time, dressing change frequency (DCF), dressing interval time (DIT), and scar recovery (SR) score of patients in different groups were compared. Results: The results revealed that the positive rate of bacterial culture in wound secretions in the Exp group was greatly lower than that in the Ctrl group 1 or 2 weeks after treatment (p < 0.05). The IR score in the Exp group was much lower at week 1 and 2 after treatment (p < 0.05). The total effective rate (TER) in the Exp group was obviously higher than that in the Ctrl group (94.55% vs. 76.36%). Conclusions: The results suggested that Bikerui disinfectant + VSD + PRP therapy could effectively improve the inflammatory degree of PU patients, promote the wound repair and scar recovery of patients, and greatly improve the clinical efficacy of PU patients.

Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes.

Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia-reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.

Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

Genome-wide identification analysis in wild-type Solanum pinnatisectum reveals some genes defending against Phytophthora infestans.

Solanum pinnatisectum exhibits strong resistance to late blight caused by Phytophthora infestans but only an incomplete genome assembly based on short Illumina reads has been published. In this study, we generated the first chromosome-level draft genome for the wild-type potato species S. pinnatisectum in China using Oxford Nanopore technology sequencing and Hi-C technology. The high-quality assembled genome size is 664 Mb with a scaffold N50 value of 49.17 Mb, of which 65.87% was occupied by repetitive sequences, and predominant long terminal repeats (42.51% of the entire genome). The genome of S. pinnatisectum was predicted to contain 34,245 genes, of which 99.34% were functionally annotated. Moreover, 303 NBS-coding disease resistance (R) genes were predicted in the S. pinnatisectum genome to investigate the potential mechanisms of resistance to late blight disease. The high-quality chromosome-level reference genome of S. pinnatisectum is expected to provide potential valuable resources for intensively and effectively investigating molecular breeding and genetic research in the future.

Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

Steering and cloaking of hyperbolic polaritons at deep-subwavelength scales.

Polaritons are well-established carriers of light, electrical signals, and even heat at the nanoscale in the setting of on-chip devices. However, the goal of achieving practical polaritonic manipulation over small distances deeply below the light diffraction limit remains elusive. Here, we implement nanoscale polaritonic in-plane steering and cloaking in a low-loss atomically layered van der Waals (vdW) insulator, α-MoO3, comprising building blocks of customizable stacked and assembled structures. Each block contributes specific characteristics that allow us to steer polaritons along the desired trajectories. Our results introduce a natural materials-based approach for the comprehensive manipulation of nanoscale optical fields, advancing research in the vdW polaritonics domain and on-chip nanophotonic circuits.

Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35-762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway.

PURPOSE: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. METHODS: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. RESULTS: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1ß (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN. AntagomiR-1297 increased PTEN expression and suppressed PI3K and AKT phosphorylation (all p < 0.001). CONCLUSIONS: AntagomiR-1297 can mitigate renal fibrosis, renal inflammation, apoptosis, and oxidative stress levels through the PTEN/PI3K/AKT pathway.

Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Discovery of palmatine derivatives as potent neuroprotective agents.

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.

Reasons, Efficacy and Safety of Switching to Dolutegravir-Based Regimens Among Virologically Suppressed PLWH: A Retrospective Cohort Study of 96 Weeks.

Purpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG. Methods: PLWH's basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA <50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96. Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/µL (IQR 420.5-758) to 642 cells/µL (IQR 466.5-854) at week 96 (p<0.0001). An improvement was observed in liver function (ALT: p<0.0001; AST: p<0.0001) and fasting glucose (p<0.0001). However, there was an elevation in creatinine (Cr) (p<0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p<0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen. Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.