Prevalence, risk factors, and outcomes of dysphagia after stroke: a systematic review and meta-analysis.

Background: Dysphagia is a common complication after stroke, which not only brings adverse outcomes but also greatly affects the quality of life of patients. At present, there is no systematic review or meta-analysis to comprehensively evaluate the epidemiological characteristics of post-stroke dysphagia (PSD). A systematic review of the prevalence, risk factors, and prognosis of PSD is essential. Methods: Through 31 December 2022, a comprehensive literature search was performed for observational studies related to PSD. Five databases were retrieved. Random-effects models were used to estimate the pooled prevalence, odds ratio (OR), and 95% CIs. Results: A total of 34 studies were included, and the results showed that the overall prevalence of PSD was 46.6% (95% CI, 0.405-0.528). The prevalence of dysphagia in ischemic stroke and hemorrhagic stroke was 43.6% (95% CI 0.370-0.501) and 58.8% (95% CI 0.519-0.654), respectively. The prevalence of PSD in Africa was 49.4% (95% CI, 0.196-0.792), in Asia was 40.1% (95% CI, 0.348-0.454), in Europe was 45.8% (95% CI, 0.327-0.590), in North America was 44.3% (95% CI, 0.370-0.517), in South America was 57.5% (95% CI, 0.441-0.708), and in Oceania was 64.1% (95%CI, 0.558, 0.724). In risk factor analysis, hypertension, previous stroke, and atrial fibrillation were significantly associated with the occurrence of PSD, pooled OR = 1.179 [(95% CI, 1.002-1.386), p < 0.05], pooled OR = 1.514 [(95% CI, 1.204-1.905), p < 0.001], and pooled OR = 1.980 [(95% CI, 1.580-2.481), p < 0.001]. In outcome studies, the prevalence of aphasia and dysarthria in PSD was 35.6% (95% CI, 0.213-0.499) and 54.5% (95% CI, 0.293-0.798), respectively. The prevalence of respiratory tract infection was 27.1% (95%CI, -0.038-0.579), and the prevalence of pneumonitis was 32.1% (95% CI, 0.224-0.418). Persistence of dysphagia at discharge and at 1 month was 74.5% (95% CI, 0.621-0.869) and 50.9% (95% CI, 0.142-0.876), respectively. Mortality rates for PSD patients during admission and discharge at 1 month, 3 months, and 1 year were 11.8% (95% CI, 0.083-0.152), 26.5% (95% CI, 0.170-0.359), 25.7% (95% CI, 0.19-0.324), and 31.3% (95% CI, 0.256-0.369), respectively. Conclusion: This study found that the overall prevalence of PSD was 46.6%. Prevalence is most influenced by the diagnosis method. Hypertension, history of stroke, atrial fibrillation, patient age, and stroke severity were risk factors significantly associated with PSD. The prevalence of aphasia, dysarthria, respiratory tract infection, and pneumonitis in PSD patients is 2-4 times that of patients without PSD.Systematic review registration: www.crd.york.ac.uk/PROSPERO, PROSPERO, CRD42021252967.

Association between complete blood count-derived inflammatory markers and the risk of frailty and mortality in middle-aged and older adults.

Objective: This study aimed to evaluate the association between six complete blood count (CBC)-derived inflammatory markers [neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV)] and the risk of frailty and mortality. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality was identified using the National Death Index until December 31, 2019. Multiple logistic regression analysis was conducted to evaluate the association between six CBC-derived inflammatory markers and frailty. The Cox regression model assessed the association between six CBC-derived inflammatory markers and mortality in frail populations. Restricted cubic spline (RCS) was used to visualize the association of the six CBC-derived inflammatory markers with mortality risk. The predictive value of CBC-derived inflammatory markers for mortality was further assessed using a random survival forest (RSF) approach. Results: This study analyzed data from a total of 16,705 middle-aged and older participants. Among them, 6,503 participants were frail, with a mortality rate of 41.47%. Multiple logistic regression analysis showed that NLR, MLR, PLR, SII, SIRI, and PIV were positively associated with frailty risk. The Cox regression model revealed that participants in the highest quartile had a significantly increased risk of death compared to those in the lowest quartile: NLR (HR = 1.73, 95% CI:1.54, 1.94), MLR (HR = 1.71, 95% CI:1.51, 1.93), PLR (HR = 1.28, 95%CI: 1.15, 1.43), SII (HR = 1.50, 95%CI:1.34, 1.68), SIRI (HR = 1.88, CI 95%:1.67, 2.12), PIV (HR = 1.55, 95%CI:1.38, 1.73). Random survival forest (RSF) analyses demonstrated that MLR had the highest predictive value for mortality risk middle-aged and older adult frail participants. Conclusion: The results suggest that CBC-derived inflammatory markers are associated with a higher risk of frailty as well as mortality in the middle and old-aged population of the United States.

Daytime napping and the incidence of Parkinson's disease: a prospective cohort study with Mendelian randomization.

BACKGROUND: The causal relationship between daytime napping and the risk of Parkinson's disease (PD) remains unclear, with prospective studies providing limited evidence. This study investigated the association between daytime napping frequency and duration and PD incidence and explored the causality relationship between this association by conducting Mendelian randomization (MR) analysis. METHODS: This prospective cohort study included 393,302 participants, and accelerometer-measured daytime napping data were available only for 78,141 individuals. Cox proportional hazards regression was used to estimate the association between the daytime napping frequency and duration and the PD risk. The role of the systemic immune-inflammation index (SII) in the association between daytime napping frequency and PD risk was assessed through mediation analyses. Moreover, the causal association between the daytime napping frequency and the PD risk was preliminarily explored by conducting two-sample MR analyses. RESULTS: The median follow-up duration was 12.18 years. The participants who reported napping sometimes or usually exhibited a significantly higher PD risk than those who never/rarely napped during the day [sometimes: hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.03-1.23; usually: HR, 1.33; 95% CI, 1.14-1.55], and SII played a mediating role in this association. However, the MR analyses did not indicate that the daytime napping frequency and PD risk were significantly associated. The participants napping for over 1 h exhibited a significantly elevated PD risk (HR, 1.54; 95% CI, 1.11-2.16). Moreover, no significant interaction was identified between napping frequency or duration and genetic susceptibility to PD (P for interaction > 0.05). CONCLUSIONS: In this study, increased daytime napping frequency and duration were associated with an increased PD risk, but no causal relationship was observed between napping frequency and PD risk in the MR analysis. Larger GWAS-based cohort studies and MR studies are warranted to explore potential causal relationships.

Electroacupuncture remodels gut microbiota and metabolites in mice with perioperative neurocognitive impairment.

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100ß, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.

High-density vertical sidewall MoS2 transistors through T-shape vertical lamination.

Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2 transistors within a small vertical footprint, corresponding to a device density over 108 cm-2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.

Predicting and refining acid modifications of biochar based on machine learning and bibliometric analysis: Specific surface area, average pore size, and total pore volume.

Acid-modified biochar is a modified biochar material with convenient preparation, high specific surface area, and rich pore structure. It has great potential for application in the heavy metal remediation, soil amendments, and carrying catalysts. Specific surface area (SSA), average pore size (APS), and total pore volume (TPV) are the key properties that determine its adsorption capacity, reactivity, and water holding capacity, and an intensive study of these properties is essential to optimize the performance of biochar. But the complex interactions among the preparation conditions obstruct finding the optimal modification strategy. This study collected dataset through bibliometric analysis and used four typical machine learning models to predict the SSA, APS, and TPV of acid-modified biochar. The results showed that the extreme gradient boosting (XGB) was optimal for the test results (SSA R2 = 0.92, APS R2 = 0.87, TPV R2 = 0.96). The model interpretation revealed that the modification conditions were the major factors affecting SSA and TPV, and the pyrolysis conditions were the major factors affecting APS. Based on the XGB model, the modification conditions of biochar were optimized, which revealed the ideal preparation conditions for producing the optimal biochar (SSA = 727.02 m2/g, APS = 5.34 nm, TPV = 0.68 cm3/g). Moreover, the biochar produced under specific conditions verified the generalization ability of the XGB model (R2 = 0.99, RMSE = 12.355). This study provides guidance for optimizing the preparation strategy of acid-modified biochar and promotes its potentiality for industrial application.

STX16 exon 5-7 deletion in a patient with pseudohypoparathyroidism type 1B.

OBJECTIVES: Pseudohypoparathyroidism (PHP) comprises a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone (PTH) resistance. PHP type 1B (PHP1B) is caused by heterozygous maternal deletions within GNAS or STX16. STX16 exon 2-6 deletion is commonly observed in autosomal dominant (AD)-PHP1B, while sporadic PHP1B commonly results from methylation abnormalities of maternal differentially methylated regions and remains unclear at the molecular level. CASE PRESENTATION: A 39-year-old male patient with PHP1B, who had his first seizure at 15 years of age, presented to our hospital. The methylation-specific multiplex ligation-dependent probe amplification results showed a half-reduced copy number of STX16 exon 5-7 and loss of methylation at GNAS exon A/B. His mother also had a half-reduced copy number of STX16 exon 5-7 but with normal methylation of GNAS. His father has a normal copy number of STX16 and normal methylation of GNAS. CONCLUSIONS: For the recognition and early diagnosis of this kind of disease, here we report the clinical symptoms, auxiliary examinations, genetic testing characteristics, and treatment of the patient.

Exploring the rules of related parameters in acupuncture for post-stroke dysphagia based on data mining.

Background: Post-stroke dysphagia (PSD) affects the efficacy and safety of swallowing, causing serious complications. Acupuncture is a promising and cost-effective treatment for PSD; however, as the number of randomized controlled trials increases, scientific analysis of the parameters and acupoint prescription is required. Therefore, this study aimed to explore the effects of acupuncture on parameters related to post-stroke dysphagia (PSD). Methods: We searched the Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature, and Chongqing VIP Database for randomized controlled trials of acupuncture for PSD in the last 15 years and relevant parameters were analyzed using data mining techniques. Results: In total, 3,205 records were identified, of which 3,507 patients with PSD were included in 39 studies. The comprehensive analysis demonstrated that the closest parameter combinations of acupuncture on PSD were 0.25 mm × 40 mm needle size, 30 min retention time, five treatments per week, and a 4-week total course of treatment. Additionally, the gallbladder and nontraditional meridians, crossing points, and head and neck sites are the most commonly used acupoint parameters. The core acupoints identified were GB20, RN23, EX-HN14, Gongxue, MS6, SJ17, EX-HN12, EX-HN13, and the commonly used combination of EX-HN12, EX-HN13, GB20, and RN23. Conclusion: This study analyzed the patterns of PSD-related needling and acupoint parameters to provide evidence-based guidelines for clinical acupuncturists in treating PSD, potentially benefitting affected patients.

[Effects of Biochar-loaded Ammonia Nitrogen on Soil Carbon Emissions, Enzyme Activity, and Microbial Communities].

The form of soil nitrogen input significantly affects soil CO2 emission. As a new form of nitrogen input, biochar-loaded ammonia nitrogen not only reduces the input of chemical nitrogen fertilizer in farmland but also reduces the cost of environmental treatment. It is of great significance to promote the zero growth of national chemical fertilizer, the prevention and control of farmland non-point source pollution, and the realization of the national goal of "carbon peak" and "carbon neutralization." Through an indoor culture experiment, the effects of different nitrogen input forms on soil carbon emission, enzyme activity, and microbial community were studied through four treatments:no fertilization (CK), single application of chemical nitrogen fertilizer (CF), biochar combined application of chemical nitrogen fertilizer (BF), and biochar-loaded ammonia nitrogen (BN). The results showed that compared with that in CF, BF significantly increased cumulative carbon emissions (66.24 %), whereas BN had no significant difference. It is worth noting that the cumulative carbon emissions were significantly reduced by 35.28 % compared with that in BF and BN. Compared with those in CF and BF, the activities of ß-glucosidase, peroxidase, and polyphenol oxidase treated with BN significantly increased by 20.25 % and 5.20 %, respectively. Compared with that in CF, the BF treatment increased microbial community richness and community diversity, whereas the BN treatment decreased microbial community richness. Compared with that in BF, the relative abundance of Proteobacteria decreased by 11.16 %, and the relative abundance of Actinobacteria and Bacteroidota increased by 8.12 % and 5.83 %, respectively, in which xylosidase activity was the most important soil factor affecting microbial community structure. The relative abundance of Chloroflexi was significantly correlated with cellobiose hydrolase activity, and the relative abundance of Gemmatimonadetes was significantly correlated with ß-glucosidase activity. There was a very significant correlation between the relative abundance of Proteobacteria and cumulative carbon emissions. To summarize, compared with those under biochar combined with chemical nitrogen fertilizer, biochar loaded with ammonia nitrogen significantly reduced cumulative carbon emissions, and its emission reduction effect was better. The results of this study will be beneficial to the landing of the national "double carbon strategy," the healthy development of the biological natural gas industry, the construction of the national green cultivation circular agriculture system, and the realization of the national zero growth strategy of chemical fertilizer.

Effects of Fermented Navel Orange Pulp on Growth Performance, Carcass Characteristics, Meat Quality, Meat Nutritional Value, and Serum Biochemical Indicators of Finishing Tibetan Pigs.

In order to cope with the limited supply of feed for global animal production, there is a pressing need to explore alternative feed resources. Orange pulp, a by-product of agriculture and industry, has shown potential to positively or neutrally impact pig productive performance when included in their diet. However, there is a lack of research on the effects of fermented navel orange pulp (FNOP) on pig growth and productive performance. This study aimed to investigate the effects of FNOP as a dry matter substitute on pig's growth performance, carcass characteristics, meat quality, meat nutritional value, and serum biochemical indicators. The experiment involved 128 finishing Tibetan pigs, divided into four feed treatment groups, with varying levels (0%, 5%, 10% and 15%) of FNOP replacing dry matter in the basal diet. The results indicate that substituting 5% to 15% FNOP had no adverse effects on pig growth performance. However, at a 15% substitution rate, there was a decrease in serum growth hormone and IGF-1 levels, along with an increase in the feed-to-gain ratio. A 10% FNOP replacement notably increased the loin-eye muscle area of pigs. Additionally, 5% and 10% FNOP substitutions reduced the drip loss of pork. The study also found that substituting 5% to 15% FNOP increased unsaturated fatty acids and umami nucleotide contents in pork and raised serum total protein and uric acid (nucleotide-metabolism-related product) levels. These findings suggest that moderate FNOP substitution might improve meat quality, nutritional value, and maintain growth and productive performance in Tibetan pigs by improving protein synthesis and nucleotide metabolism, while also reducing feed costs. The optimal substitution ratio identified was 10%.

Effects of virtual reality-based rehabilitation on cognitive function and mood in multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a disabling neurological disease that causes cognitive impairment and mental problems that occur in all MS phenotypes but are most common in patients with secondary progressive MS. Various degrees of cognitive impairment and mental health concerns are common among patients with MS (PwMS). Virtual reality (VR)-based rehabilitation is an innovative approach aimed at enhancing cognitive function and mood in PwMS. This study aims to perform a meta-analysis to assess the effects of VR-based rehabilitation on cognitive function and mood in PwMS. METHODS: Using PubMed, Embase, the Cochrane Library, Web of Science, and the Physiotherapy Evidence Database (PEDro), a thorough database search was performed to identify randomized controlled trials (RCTs) examining the effects of VR on PwMS. Trials published until October 31, 2023, that satisfied our predetermined inclusion and exclusion criteria were included. Data were extracted, literature was examined, and the methodological quality of the included trials was assessed. StataSE version 16 was used for the meta-analysis. RESULTS: Our meta-analysis included 461 patients from 10 RCTs. PRIMARY OUTCOMES: The Montreal Cognitive Assessment (MoCA) (weighted mean difference [WMD]=1.93, 95 % confidence interval [CI]=0.51-3.36, P = 0.008, I² = 75.4 %) the Spatial Recall Test (SPART) (WMD=3.57, 95 % CI=1.65-5.50, P < 0.001, I² = 0 %), immediate recall (standard mean difference [SMD]=0.37, 95 % CI=0.10-0.64, P = 0.007, I² = 0 %) and delayed recall ([SMD]=0.30, 95 % CI=0.06-0.54, P = 0.013, I² = 35.4 %) showed improvements in comparison to the control group in terms of global cognitive function immediate recall, delayed recall, and visuospatial abilities. SECONDARY OUTCOMES: Compared to the control group, anxiety improved (standard mean difference [SMD]=0.36, 95 % CI=0.10-0.62, P = 0.007, I² = 43.1 %). However, there were no significant differences in processing speed, attention, working memory or depression. CONCLUSIONS: This systematic review provides valuable evidence for improving cognitive function and mood in PwMS through VR-based rehabilitation. In the future, VR-based rehabilitation may be a potential method to treat cognitive function and emotional symptoms of MS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO; identifier: CRD42023474467.

USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of Usp8 (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation. However, mice with heterozygous deletion of Usp8 in IECs display normal phenotype and become resistant to azoxymethane/dextran sodium sulfate-induced colorectal tumorigenesis. Mechanistically, USP8 interacts with and deubiquitinates glutathione peroxidase 4 (GPX4), leading to GPX4 stabilization. Thus, USP8 inhibition destabilizes GPX4 and sensitizes cancer cells to ferroptosis in vitro. Notably, USP8 inhibition in combination with ferroptosis inducers retards tumor growth and enhances CD8+ T cell infiltration, which potentiates tumor response to anti-PD-1 immunotherapy in vivo. These findings uncover that USP8 counteracts ferroptosis by stabilizing GPX4 and highlight targeting USP8 as a potential therapeutic strategy to boost ferroptosis for enhancing cancer immunotherapy.

Insulin eye drops improve corneal wound healing in STZ-induced diabetic mice by regulating corneal inflammation and neuropeptide release.

INTRODUCTION: In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds. METHODS: A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1ß, ß3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury. RESULTS: Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining. CONCLUSIONS: Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies.

Inflammatory pain (IP) is one of the most prevalent and intractable human conditions, and it leads to progressive dysfunction and reduced quality of life. Additionally, IP is incredibly challenging to treat successfully with drugs or surgery. The development of IP is complex and multifactorial, and peripheral and central sensitization may influence chronicity and treatment resistance in IP. Understanding the mechanisms underlying IP is vital for developing novel therapies. Strong evidence suggests that exercise can be a first-line relief for patients with IP during rehabilitation. However, the mechanisms through which exercise improves IP remain unclear. Here, we reviewed the current animal experimental evidence for an exercise intervention in IP and proposed biological mechanisms for the effects of synaptic plasticity in the anterior cingulate cortex, endocannabinoids, spinal dorsal horn excitability balance, immune cell polarization balance, cytokines, and glial cells. This information will contribute to basic science and strengthen the scientific basis for exercise therapy prescriptions for IP in clinical practice.

Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N6-methyladenosine (m6A) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood. Here, we report that METTL3 elevates expression of pro-tumorigenic chemokines including CXCL1, CXCL5, and CCL20, and destabilizes PD-L1 mRNA in an m6A-dependent manner, thereby shaping a non-inflamed TME. Thus, inhibiting METTL3 reprograms a more inflamed TME that renders anti-PD-1 therapy more effective in several murine lung tumor models. Clinically, NSCLC patients who exhibit low-METTL3 expression have a better prognosis when receiving anti-PD-1 therapy. Collectively, our study highlights targeting METTL3 as a promising strategy to improve immunotherapy in NSCLC patients.

3D bioprinting by reinforced bioink based on photocurable interpenetrating networks for cartilage tissue engineering.

Cartilage has a limited ability to repair itself, highlighting the urgent need for suitable materials for cartilage regeneration. Achieving a balance between cell survival environment and hydrogel crosslinking density is crucial for photosensitive cell-laden cartilage repair materials to achieve both high strength and good cell viability. Here, an interpenetrating hydrogel consisted of methacrylate gelatin (GelMA) and glycidyl methacrylate silk fibroin (SG) was introduced. Compared to GelMA hydrogel, GelMA/SG had desired mechanical properties, with achieving up to 5 times of compression modulus and 6 times of compression failure energy. Meanwhile, the chondrocytes inside GelMA/SG exhibited great viability which was over 90 %. GelMA/SG as a bioink had favorable printability for digital light processing (DLP) bioprinting. The mesh DLP-printed scaffolds with high precision were created and GelMA/SG had a better shape retention ability than GelMA. Moreover, GelMA/SG cell-laden scaffolds had high strength while chondrocytes proliferated significantly in vitro culture. They were implanted under the skin of nude mice to evaluate ectopic chondrogenesis in vivo. The GelMA/SG cell-laden scaffolds indicated little deformation and high expression of collagen type II and glycosaminoglycans, which was advantageous for cartilage regeneration. The scaffold and its fabrication strategy provide potential solutions for clinical cartilage repair problems in the future.

Corrigendum: Proteomic profiling reveals the potential mechanisms and regulatory targets of sirtuin 4 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's mouse model.

[This corrects the article DOI: 10.3389/fnins.2022.1035444.].

GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes.

Objective: To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results: Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion: The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.

Tobacco roots increasing diameter and secondary lateral density in response to drought stress.

Exploring the responses of root morphology and its physiological mechanisms under drought stress is significant for further improving water and nutrient absorption in roots. Here, we simulated drought through hydroponics combined with PEG treatments in tobacco to characterize the changes in tobacco root architecture. Our results showed the total root length, first lateral root number, and first lateral root length were significantly reduced upon increasing drought severity, but the average root diameter and secondary lateral root density increased under certain drought conditions. The change of auxin content in roots under drought stress was correlated with the root diameter and second lateral root density responses. Exogenous addition of the auxin analog (NAA) and the auxin transport inhibitor (NPA), as well as DR5:GUS staining experiments further demonstrated that auxin participated in this physiological process. Meanwhile, brassinolide (BR) exhibited a similar trend. Exogenous addition of BR (EBR) and the BR synthesis inhibitor BRZ experiments demonstrated that BR may participate upstream of auxin under drought stress. PEG treatment significantly up-regulated NtBRI1 at 9-24 h, and promoted the up-regulation of NtBSK2 and NtBSK3 at 48 h and 24 h, respectively, these genes may contribute to the change in root morphology under drought stress. This study shows that auxin and BR are involved in the changes in root morphology in tobacco exposed to drought stress. The elucidation of the molecular mechanism at play thus represents a future target for breeding drought-tolerant tobacco varieties.