Objective sleep enhancement in Parkinson's disease: A sham-controlled trial of low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex.

INTRODUCTION: Parkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients. METHODS: In this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS. RESULTS: The rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5-2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes. CONCLUSION: Low-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.

Genetic diversity and prevalence of emerging Rickettsiales in Yunnan Province: a large-scale study.

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.

Anti-osteoporosis drugs reduce mortality in cancer patients: A national cohort study of elderly with vertebral fractures.

Introduction: The most prevalent type of fragility fractures is osteoporotic vertebral fractures (OVFs). However, only a few studies have examined the relationship between anti-osteoporosis treatments and malignancy-related mortality following an OVF. The goal of this study is to determine the effect of anti-osteoporosis therapy on mortality in OVF patients with and without cancer. Method: Data from older people over the age of 65 who were hospitalised for OVFs between 1 January 2003 and 31 December 2018 were analysed retrospectively. A total of 6139 persons getting osteoporosis treatment and 28,950 who did not receive treatment were analysed, together with 2 sets of patients, comprising cancer patients (794) and cancer-free patients (5342), using anti-osteoporosis medication or not, in 1:1 propensity score-matched analyses. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: In all, 35,089 patients with OVFs were included in the population; 29,931 people (85.3%) were women, and the mean (standard deviation) age was 78.13 (9.27) years. Overall survival was considerably higher in those undergoing osteoporosis therapy. This was true both for those without cancer (adjusted HR 0.55; 95% CI 0.51-0.59; P<.0001) as well as those with cancer (adjusted HR 0.72; 95% CI 0.62-0.84; P<.0001). Even among cancer patients, those who received anti-osteoporotic drugs had a lower mortality rate than those who did not. Conclusion: Our findings suggest that anti-osteoporosis therapy should be initiated regardless of the presence of cancer in the elderly, as it increases survival following OVFs.

A new machine learning model to predict the prognosis of cardiogenic brain infarction.

Cardiogenic cerebral infarction (CCI) is a disease in which the blood supply to the blood vessels in the brain is insufficient due to atherosclerosis or stenosis of the coronary arteries in the patient's heart, which leads to neurological deficits. To predict the pathogenic factors of cardiogenic cerebral infarction, this paper proposes a machine learning based analytical prediction model. 494 patients with CCI who were hospitalized for the first time were consecutively included in the study between January 2017 and December 2021, and followed up every three months for one year after hospital discharge. Clinical, laboratory and imaging data were collected, and predictors associated with relapse and death in CCI patients at six months and one year after discharge were analyzed using univariate and multivariate logistic regression methods, meanwhile established a new machine learning model based on the enhanced moth-flame optimization (FTSAMFO) and the fuzzy K-nearest neighbor (FKNN), called BITSAMFO-FKNN, which is practiced on the dataset related to patients with CCI. Specifically, this paper proposes the spatial transformation strategy to increase the exploitation capability of moth-flame optimization (MFO) and combines it with the tree seed algorithm (TSA) to increase the search capability of MFO. In the benchmark function experiments FTSAMFO beat 5 classical algorithms and 5 recent variants. In the feature selection experiment, ten times ten-fold cross-validation trials showed that the BITSAMFO-FKNN model proved actual medical importance and efficacy, with an accuracy value of 96.61%, sensitivity value of 0.8947, MCC value of 0.9231, and F-Measure of 0.9444. The results of the trial showed that hemorrhagic conversion and lower LVDD/LVSD were independent risk factors for recurrence and death in patients with CCI. The established BITSAMFO-FKNN method is helpful for CCI prognosis and deserves further clinical validation.

Enhancement of Light Efficiency of Deep-Ultraviolet Light-Emitting Diodes by Encapsulation with a 3D Photonic Crystal Reflecting Layer.

Recently, UVC LEDs, which emit deep ultraviolet light, have found extensive applications across various fields. This study demonstrates the design and implementation of thin films of three-dimensional photonic crystals (3D PhCs) as reflectors to enhance the light output power (LOP) of UVC LEDs. The 3D PhC reflectors were prepared using the self-assembly of silica nanospheres on a UVC LED lead frame substrate via the evaporation-induced method (side) and the gravitational sedimentation method (bottom), respectively. These PhCs with the (111) crystallographic plane were deposited on the side wall and bottom of the UVC LED lead frame, acting as functional materials to reflect UVC light. The LOP of UVC LEDs with 3D PhC reflectors at a driving current of 100 mA reached 19.6 mW. This represented a 30% enhancement compared to commercial UVC LEDs with Au-plated reflectors, due to the UVC light reflection by the photonic band gaps of 3D PhCs in the (111) crystallographic plane. Furthermore, after aging tests at 60 °C and 60% relative humidity for 1000 h, the relative LOP of UVC LEDs with 3D PhC reflectors decreased by 7%, which is better than that of commercial UVC LEDs. Thus, this study offers potential methods for enhancing the light output efficiency of commercial UVC light-emitting devices.

Machine Learning Prediction of Prediabetes in a Young Male Chinese Cohort with 5.8-Year Follow-Up.

The identification of risk factors for future prediabetes in young men remains largely unexamined. This study enrolled 6247 young ethnic Chinese men with normal fasting plasma glucose at the baseline (FPGbase), and used machine learning (Mach-L) methods to predict prediabetes after 5.8 years. The study seeks to achieve the following: 1. Evaluate whether Mach-L outperformed traditional multiple linear regression (MLR). 2. Identify the most important risk factors. The baseline data included demographic, biochemistry, and lifestyle information. Two models were built, where Model 1 included all variables and Model 2 excluded FPGbase, since it had the most profound effect on prediction. Random forest, stochastic gradient boosting, eXtreme gradient boosting, and elastic net were used, and the model performance was compared using different error metrics. All the Mach-L errors were smaller than those for MLR, thus Mach-L provided the most accurate results. In descending order of importance, the key factors for Model 1 were FPGbase, body fat (BF), creatinine (Cr), thyroid stimulating hormone (TSH), WBC, and age, while those for Model 2 were BF, white blood cell, age, TSH, TG, and LDL-C. We concluded that FPGbase was the most important factor to predict future prediabetes. However, after removing FPGbase, WBC, TSH, BF, HDL-C, and age were the key factors after 5.8 years.

The Antimicrobial Peptide Tilapia Piscidin 4 Induced the Apoptosis of Bladder Cancer Through ERK/SIRT1/PGC-1α Signaling Pathway.

Marine antimicrobial peptides have been demonstrated in numerous studies to possess anti-cancer properties. This research investigation aimed to explore the fundamental molecular mechanisms underlying the antitumor activity of Tilapia piscidin 4 (TP4), an antimicrobial peptide, in human bladder cancer. TP4 exhibited a remarkable inhibitory effect on the proliferation of bladder cancer cells through cell cycle arrest at the G2/M phase. Additionally, TP4 upregulated the expression of cleaved caspase-3, caspase-9, and PARP, leading to the activation of apoptotic pathways in bladder cancer cells. TP4 exhibit a marked rise in mitochondria reactive oxygen species, leading to the subsequent loss of potential for the mitochondrial membrane. Furthermore, the inhibition of mitochondrial oxidative phosphorylation resulted in a decrease in downstream ATP production. Meanwhile, TP4-treated bladder cancer cells showed an increase in Bax and ERK but a decrease in SIRT1, PGC-1α, and Bcl2. ERK activation, SIRT1/PGC-1α-axis, and TP4-induced apoptosis were all significantly reversed by the ERK inhibitor SCH772984. Finally, the inhibitory effect of TP4 on tumor growth has been confirmed in a zebrafish bladder cancer xenotransplantation model. These findings suggest that TP4 may be a potential agents for human bladder cancer through apoptosis induction, ERK activation, and the promotion of SIRT1-mediated signaling pathways.

Mother-reliant or Self-reliant: The germination strategy of seeds in a species-rich alpine meadow is associated with the existence of pericarps.

BACKGROUND AND AIMS: Some plants germinate their seeds enclosed by a pericarp, while others lack the outer packaging. As a maternal tissue, may impart seeds with different germination strategies. Plants in a community with different flowering times may separately disperse and germinate their seeds; therefore, flowering time can be considered as one manifestation of maternal effects on offspring. The mass of the seed is another important factor influencing germination and represents the intrinsic resource of seed that supports the germination. Using seeds from a species-rich alpine meadow located in the Hengduan Mountains of China, a global biodiversity hotspot, we aim to illustrate whether and how the type of seed (with and without a pericarp) modulates the interaction of flowering time and seed mass with germination. METHODS: Seeds were germinated under a generally favorable condition and germination speed (estimated by mean germination time, MGT) was calculated. We quantified the maternal conditions by separation of flowering time for 67 species in the meadow, in which 31 produced seeds with pericarps and 36 yielded seeds without pericarps, respectively. We also weighed one hundred seeds to assess their mass. KEY RESULTS: The MGT varied between the two types of seed. For seeds with pericarps, MGT was associated with flowering time but not with seed mass. Plants with earlier flowering times in the meadow exhibited more rapid seed germination. For seeds without pericarp, the MGT depended on seed mass, with smaller seeds germinating more rapidly than larger seeds. CONCLUSIONS: The distinct responses of germination to flowering time and seed mass observed in seeds with and without pericarp suggest that germination strategies might be mother-reliant for seeds protected by pericarps but self-reliant for those without such protection. This novel finding improves our understanding of seed germination by integrating ecologically mediated maternal conditions and inherent genetic properties.

Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study.

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

SARS-CoV-2 prevalence in wildlife 2020-2022: a worldwide systematic review and meta-analysis.

The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Predictors of Early versus Delayed Neurological Deterioration after Thrombolysis for Ischemic Stroke.

INTRODUCTION: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24-72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs. 0-1 and 3-6 vs. 0-2 and death). RESULTS: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001). CONCLUSION: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days.

Surface profile measurement and parameter analysis of silicon wafers in the upright state.

A novel approach, to the best of our knowledge, is presented for assessing silicon wafer surface profiles using an interferometer and vertically rotatable wafer holder. This approach significantly enhances precision and reduces costs, and outperforms traditional techniques in measurement consistency and accuracy. It effectively reduces sample distortion and positional shifts owing to the removal and reinstallation of the wafers. Using this method, a global backsurface-referenced ideal range of 0.385 µm, warp of 0.193 µm, and other parameters were obtained, demonstrating its practicality in efficiently capturing key surface profile metrics for silicon wafers. This innovation promises substantial improvements in high-volume wafer surface profile testing, overcoming prevalent technological challenges in this industry.

Insomnia-related rodent models in drug discovery.

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia.

Cryo-EM analysis of Pseudomonas phage Pa193 structural components.

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold vertex. We also visualized a large portion of Pa193 ~ 500 Å long tail fibers and resolved the interface between the baseplate and tail fibers. The work presented here provides a framework to support a better understanding of phages as biomedicines for phage therapy and inform engineering opportunities.

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome.

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Targeting epigenetic and post-translational modifications regulating pyroptosis for the treatment of inflammatory diseases.

Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.