RNA-binding protein SYNCRIP contributes to neuropathic pain through stabilising CCR2 expression in primary sensory neurones.

BACKGROUND: Nerve injury-induced changes in gene expression in the dorsal root ganglion (DRG) contribute to the genesis of neuropathic pain. SYNCRIP, an RNA-binding protein, is critical for the stabilisation of gene expression. Whether SYNCRIP participates in nerve injury-induced alterations in DRG gene expression and nociceptive hypersensitivity is unknown. METHODS: The expression and distribution of SYNCRIP in mouse DRG after chronic constriction injury (CCI) of the unilateral sciatic nerve were assessed. Effect of microinjection of Syncrip small interfering RNA into the ipsilateral L3 and L4 DRGs on the CCI-induced upregulation of chemokine (C-C motif) receptor 2 (CCR2) and nociceptive hypersensitivity were examined. Additionally, effects of microinjection of adeno-associated virus 5 expressing full length Syncrip mRNA (AAV5-Syncrip) on basal DRG CCR2 expression and nociceptive thresholds were observed. RESULTS: SYNCRIP is expressed predominantly in DRG neurones, where it co-exists with CCR2. Levels of Syncrip mRNA and SYNCRIP protein in injured DRG increased time-dependently on days 3-14 after CCI. Blocking this increase through microinjection of Syncrip small interfering RNA into injured DRG attenuated CCI-induced upregulation of DRG CCR2 and development and maintenance of nociceptive hypersensitivities. Mimicking this increase through DRG microinjection of AAV5-Syncrip elevated CCR2 expression in microinjected DRGs, enhanced the responses to mechanical, heat, and cold stimuli, and induced ongoing pain in naive mice. Mechanistically, SYNCRIP bound to 3-UTR of Ccr2 mRNA and stabilised its expression in DRG neurones. CONCLUSIONS: SYNCRIP contributes to the induction and maintenance of neuropathic pain likely through stabilising expression of CCR2 in injured DRG. SYNCRIP may be a potential target for treating this disorder.

Effects of home-based telemedicine and mHealth interventions on blood pressure in stroke patients: a systematic evaluation and meta-analysis of randomized controlled trials.

BACKGROUND: Stroke is a common cerebrovascular disease. Elevated blood pressure is the most significant manageable factor for both initial and recurrent strokes. Despite the potential benefits of telemedicine and mobile health technology (mHealth) in managing blood pressure among stroke patients, there remains skepticism. OBJECTIVES: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the effectiveness of telemedicine and mHealth interventions in managing blood pressure in stroke patients. METHODS: We identified randomized controlled trials (RCTs) evaluating telemedicine and mHealth technology interventions for blood pressure in patients with stroke or transient ischemic attack (TIA) from the inception date of each database up to January 2, 2024 by systematic searches of the PubMed, EMBASE, Web of Science, and Cochrane Library databases. The Cochrane Risk of Bias tool (ROB 2.0) was used to evaluate study quality. Sources of heterogeneity were explored through Meta-regression, subgroup analyses, sensitivity analyses and publication bias assessment. Meta-analysis was performed using R 4.2.2 statistical software. RESULTS: A total of 13 randomized controlled trials with 3803 participants were included. The meta-analysis found that telemedicine and mHealth improved control of both systolic [MD = -4.37, 95 % CI (-5.50, -3.24), I2 = 43 %, P<0.00001] and diastolic blood pressures [MD = -1.72, 95 % CI (-2.45, -0.98), I2 = 0 %, P<0.00001] in stroke patients compared to the conventional care group. Stroke patients who received telemedicine and mHealth interventions showed improved medication adherence than usual care [SMD=0.52, 95 % CI (0.03, 1.00), I2 = 90 %, P<0.00001]. Meta-regression and subgroup analyses identified several key factors influencing systolic and diastolic blood pressure control in stroke patients, including whether stroke patients have hypertension, the specific forms of telemedicine and mHealth interventions employed, the duration of these interventions, and the frequency of intervention intervals. CONCLUSIONS: Overall, telemedicine and mHealth reduced stroke patients' systolic blood pressure by an average of 4.37 mm Hg and diastolic blood pressure by an average of 1.72 mm Hg and improved medication adherence compared with usual care. As an emerging medical model, telemedicine and mHealth intervention create a good prospect for the management of blood pressure in stroke patients in the future.

Precooked state based on protein denaturation kinetics impacts moisture status, protein oxidation and texture of prepared chicken breast.

The quality of meat in prepared dishes deteriorates due to excessive protein denaturation resulting from precooking, freezing, and recooking. This study aimed to link the precooked state with chicken breast's recooked quality. Cooked Value (CV), based on protein denaturation kinetics, was established to indicate the doneness of meat during pre-heating. The effects of CVs after pre-heating on recooked qualities were investigated compared to fully pre-heated samples (control). Mild pre-heating reduced water migration and loss. While full pre-heating inhibited protein oxidation during freezing, intense oxidation during pre-heating led to higher oxidation levels. Surface hydrophobicity analysis revealed that mild pre-heating suppressed aggregation during recooking. These factors contributed to a better texture and microstructure of prepared meat with mild pre-heating. Finally, a potential mechanism of how pre-heating affects final qualities was depicted. This study underlines the need for finely controlling the industrial precooking process to regulate the quality of prepared meat.

Constructing Functional Radiation-Resistant Thorium Clusters for Catalytic Redox Reactions.

When catalytic reactions are interfered with by radiation sources, thorium clusters are promising as potential catalysts due to their superior radiation resistance. However, there is currently very little research on the design synthesis and catalytic application of radiation-stable thorium clusters. In this work, we have elaborately engineered and fabricated three high-nuclear thorium cluster catalysts denoted as Th12L3-MA12, Th12L3-MA6-BF6, and Th12L3-Fcc12, which did not undergo any significant alterations in their molecular structures and compositions after irradiation with 690 kGy γ-rays. We systematically investigated the photocatalytic/thermocatalytic properties of these radiation-resistant thorium clusters for the first time and found that γ-rays could not alter their catalytic activities. In addition, it was found that ligand engineering could modulate the catalytic activity of thorium clusters, thus expanding the range of catalytic applications of thorium clusters, including reduction reactions (nitroarene reduction) and some oxidation reactions (N-heterocyclic oxidative dehydrogenation and diphenylmethane oxidation). Meanwhile, all of these organic transformation reactions achieved a >80% conversion and nearly 100% product selectivity. Radiation experiments combined with DFT calculations showed that the synergistic catalysis of thorium-oxo core and ligands led to the generation of specific active species (H+, O2•-, or tBuO/tBuOO•) and activation of substrate molecules, thus achieving superior catalytic performance. This work is not only the first to develop radiation-resistant thorium cluster catalysts to perform efficient redox reactions but also provides design ideas for the construction of high-nuclearity thorium clusters under mild conditions.

Development of a luciferase-based Gram-positive bacterial reporter system for the characterization of antimicrobial agents.

Mechanistic investigations are of paramount importance in elucidating the modes of action of antibiotics and facilitating the discovery of novel drugs. We reported a luciferase-based reporter system using bacterial cells to unveil mechanisms of antimicrobials targeting transcription and translation. The reporter gene Nluc encoding NanoLuciferase (NanoLuc) was integrated into the genome of the Gram-positive model organism, Bacillus subtilis, to generate a reporter strain BS2019. Cellular transcription and translation levels were assessed by quantifying the amount of Nluc mRNA as well as the luminescence catalyzed by the enzyme NanoLuc. We validated this system using three known inhibitors of transcription (rifampicin), translation (chloramphenicol), and cell wall synthesis (ampicillin). The B. subtilis reporter strain BS2019 successfully revealed a decline in Nluc expression by rifampicin and NanoLuc enzyme activity by chloramphenicol, while ampicillin produced no observable effect. The assay was employed to characterize a previously discovered bacterial transcription inhibitor, CUHK242, with known antimicrobial activity against drug-resistant Staphylococcus aureus. Production of Nluc mRNA in our reporter BS2019 was suppressed in the presence of CUHK242, demonstrating the usefulness of the construct, which provides a simple way to study the mechanism of potential antibiotic candidates at early stages of drug discovery. The reporter system can also be modified by adopting different promoters and reporter genes to extend its scope of contribution to other fields of work. IMPORTANCE: Discovering new classes of antibiotics is desperately needed to combat the emergence of multidrug-resistant pathogens. To facilitate the drug discovery process, a simple cell-based assay for mechanistic studies is essential to characterize antimicrobial candidates. In this work, we developed a luciferase-based reporter system to quantify the transcriptional and translational effects of potential compounds and validated our system using two currently marketed drugs. Reporter strains generated in this study provide readily available means for identifying bacterial transcription inhibitors as prospective novel antibacterials. We also provided a series of plasmids for characterizing promoters under various conditions such as stress.

Enhancing the Inhibition of Corneal Neovascularization Efficacy by Self-Assembled into Supramolecular Hydrogel of Anti-Angiogenic Peptide.

Background: Corneal neovascularization (CNV) is a common eye disease that leads to blindness. New treatment strategies are urgently needed due to the limitations of current treatment methods. Methods: We report the synthesis of peptide Nap-FFEEPCAIWF ( Comp.3 ) via chemical conjugation of Nap-FFEE ( Comp.2 ) to antiangiogenic peptide PCAIWF (Comp.1). Comp.3 self-assembled into a hydrogel ( gel of 3 ) composed of nanofibers, which enhanced the antiangiogenic function of the epitope. Results: We developed a novel peptide with an amphiphilic framework, Comp.3 , which could self-assemble into a supramolecular hydrogel with a well-ordered nanofiber structure. The nanofibers exhibited good biocompatibility with corneal epithelial cells, presenting a promising strategy to enhance the efficacy of free peptide-based drugs in the treatment of ocular vascular diseases, such as CNV and other angiogenesis-related diseases. Conclusion: Nap-FFEEPCAIWF nanofibers provide an alternative approach to enhancing the therapeutic efficiency of free peptide-based drugs against ocular vascular diseases.

Association between dietary protein intake and mortality among patients with diabetic kidney disease.

AIMS: This study aimed to investigate the association between dietary protein intake and mortality among patients with diabetic kidney disease. METHODS: The research encompassed a total of 2901 participants diagnosed with diabetic kidney disease, drawn from the National Health and Nutrition Examination Survey (NHANES). To determine outcomes related to all-cause and cardiovascular mortality, connections were established with the National Death Index up until December 31, 2019. Estimations of hazard ratios (HRs) and their corresponding 95 % confidence intervals (CIs) were conducted using Cox proportional hazard ratio models. RESULTS: During the 261,239 person-years of follow-up, 1236 deaths were recorded. After multivariate adjustment, the weighted hazard ratio (HR) and 95 % CIs for participants with 1.0-1.2 g/kg of protein intake was 0.65 (0.44, 0.96) for all-cause mortality. A higher proportion of animal protein intake was found to be associated with an increased mortality risk. Stratified analyses showed that higher protein intake benefited older participants. CONCLUSIONS: In diabetic kidney disease patients, 1.0-1.2 g/kg of protein was associated with lower mortality and 0.6-1.2 g/kg of protein especially benefitted patients ≥60 years.

Multiple plateaus of high-sideband generation from Floquet matters.

We theoretically report that high-order sideband generation (HSG) from Floquet matters driven by a strong terahertz light while engineered by weak infrared light can achieve multiple plateau HSG. The Floquet-engineering systems exhibit distinctive spectroscopic characteristics that go beyond the HSG processes in field-free band-structure systems. The spatial-temporal dynamics analyses under Floquet-Bloch and time-reversal-symmetry theories clarify the spectra and its odd-even characteristics in the HSG spectrum. Our work demonstrates the HSG of Floquet matters via Floquet engineering and indicates a promising way to extract Floquet material parameters in future experiments.

ESRRG-controlled downregulation of KCNN1 in primary sensory neurons is required for neuropathic pain.

Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.

Long-term, home-based transcranial direct current stimulation coupled with computerized cognitive training in frontotemporal dementia: A case report.

We present the case of a 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) with cognitive/language deficits who demonstrated improved performance on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS (anode on the left prefrontal cortex and cathode on the right homologue) for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by 3 points on the Mini-Mental State Exam (MMSE) (23 to 26). She also showed improvement on several cognitive/language tasks, such as immediate recall of single words and word pairs, total accurate words in sentence repetition, delayed recall, semantic processing, and sentence level comprehension. There was no decline in several other cognitive and language tasks. Family members reported subjective improvements in expressiveness, communication, and interaction with others as well as increased attention to grooming and style which contrasted with her pre-treatment condition. This report suggests that home-based tDCS combined with CCT for an extended period may slow decline, and improve cognitive/language performance and everyday function in FTD.

Long-term, Home-based Transcranial Direct Current Stimulation Coupled with Computerized Cognitive Training in Frontotemporal Dementia: A Case Report: A 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) improved on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by three points on the Mini-Mental State Exam (MMSE) (23 to 26). She also improved immediate recall of single words and word pairs, total accurate words in sentence repetition, delayed recall, semantic processing, and sentence level comprehension. There was no decline in several other cognitive and language tasks. Family members described improvements in expressiveness, communication, and interaction with others and increased attention to grooming and style which was different from her pre-treatment condition. This case report suggests that home-based tDCS combined with CCT for an extended period may slow decline and improve cognitive/language performance and everyday function in FTD.

Association of dietary iron intake with diabetic kidney disease among individuals with diabetes.

PURPOSE: The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults. METHODS: This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types. RESULTS: Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses. CONCLUSION: We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.

The impact of androgen levels on serum metabolic profiles in patients with polycystic ovary syndrome.

OBJECTIVE: This study aimed to investigate the impact of serum androgen levels on metabolic profiles in patients with polycystic ovary syndrome (PCOS). METHODS: We included 216 patients with PCOS and 216 healthy individuals selected as the control group. According to the measured serum androgen levels, patients with PCOS were divided into the hyperandrogenism group and non-hyperandrogenism group. Clinical metabolic indicators were assessed and compared between the two groups. Additionally, we assessed the correlation between androgen levels and clinical metabolic indicators. RESULTS: The body mass index, waist-to-hip ratio, mF-G score, and acne score, as well as T, LH, LSH/FSH, FPG, Cr, UA, TG, TC, and LDL-C levels were significantly higher in the PCOS group than in the control group. The incidence of hyperandrogenism and clinical hyperandrogenism in the PCOS group was significantly higher than that in the control group. Regarding clinical hyperandrogenism, hirsutism, acne, and acanthosis nigricans were significantly more common in the PCOS group than in the control group. Serum androgen levels were significantly correlated with the mF-G score, acne score, FSH, glucose concentration at 30 min, glucose concentration at 60 min, glucose concentration at 120 min, FINS, N120, HOMA-IR, HbA1c, AUCG, UA, TG, and hHDL-Clevels. CONCLUSION: Elevated serum androgen levels are commonly observed in patients with PCOS and are associated with multiple metabolic abnormalities. Therefore, it is recommended to regularly monitor glucose and lipid metabolism-related indicators in patients with PCOS who have elevated androgen levels.

Weldability and Mechanical Properties of Pure Copper Foils Welded by Blue Diode Laser.

The need to manufacture components out of copper is significantly increasing, particularly in the solar technology, semiconductor, and electric vehicle sectors. In the past few decades, infrared laser (IR) and green laser (GL) have been the primary technologies used to address this demand, especially for small or thin components. However, with the increased demand for energy saving, alternative joint techniques such as blue diode laser (BDL) are being actively explored. In this paper, bead-on-plate welding experiments on 0.2 mm thick pure copper samples employing a BDL are presented. Two sets of parameters were carefully selected in this investigation, namely Cu-1: Power (P) = 200 W; Speed (s) = 1 mm/s; and angle = 0°, and Cu-2: P = 200 W; s = 5 mm/s; and angle = 10°. The results from both sets of parameters produced defect-free full penetration welds. Hardness test results indicated relatively softer weld zones compared with the base metal. Tensile test samples fractured in the weld zones. Overall, the samples welded with Cu-1 parameters showed better mechanical properties, such as strength and elongation, than those welded with the Cu-2 parameters. The tensile strength and elongation obtained from Cu-1 were marginally lower than those of the unwelded pure copper. The outcomes from this research provide an alternative welding technique that is able to produce reliable, strong, and precise joints, particularly for small and thin components, which can be very challenging to produce.

Robust Epileptic Seizure Detection Based on Biomedical Signals Using an Advanced Multi-View Deep Feature Learning Approach.

Epilepsy is a neurological disorder characterized by abnormal neuronal discharges that manifest in life-threatening seizures. These are often monitored via EEG signals, a key aspect of biomedical signal processing (BSP). Accurate epileptic seizure (ES) detection significantly depends on the precise identification of key EEG features, which requires a deep understanding of the data's intrinsic domain. Therefore, this study presents an Advanced Multi-View Deep Feature Learning (AMV-DFL) framework based on machine learning (ML) technology to enhance the detection of relevant EEG signal features for ES. Our method initially applies a fast Fourier transform (FFT) to EEG data for traditional frequency domain feature (TFD-F) extraction and directly incorporates time domain (TD) features from the raw EEG signals, establishing a comprehensive traditional multi-view feature (TMV-F). Deep features are subsequently extracted autonomously from optimal layers of one-dimensional convolutional neural networks (1D CNN), resulting in multi-view deep features (MV-DF) integrating both time and frequency domains. A multi-view forest (MV-F) is an interpretable rule-based advanced ML classifier used to construct a robust, generalized classification. Tree-based SHAP explainable artificial intelligence (T-XAI) is incorporated for interpreting and explaining the underlying rules. Experimental results confirm our method's superiority, surpassing models using TMV-FL and single-view deep features (SV-DF) by 4% and outperforming other state-of-the-art methods by an average of 3% in classification accuracy. The AMV-DFL approach aids clinicians in identifying EEG features indicative of ES, potentially discovering novel biomarkers, and improving diagnostic capabilities in epilepsy management.

NT-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons.

Cancer patients undergoing treatment with antineoplastic drugs often experience chemotherapy-induced neuropathic pain (CINP), and the therapeutic options for managing CINP are limited. Here, we show that systemic paclitaxel administration upregulates the expression of neurotrophin-3 (Nt3) mRNA and NT3 protein in the neurons of dorsal root ganglia (DRG), but not in the spinal cord. Blocking NT3 upregulation attenuates paclitaxel-induced mechanical, heat, and cold nociceptive hypersensitivities and spontaneous pain without altering acute pain and locomotor activity in male and female mice. Conversely, mimicking this increase produces enhanced responses to mechanical, heat, and cold stimuli and spontaneous pain in naive male and female mice. Mechanistically, NT3 triggers tropomyosin receptor kinase C (TrkC) activation and participates in the paclitaxel-induced increases of C-C chemokine ligand 2 (Ccl2) mRNA and CCL2 protein in the DRG. Given that CCL2 is an endogenous initiator of CINP and that Nt3 mRNA co-expresses with TrkC and Ccl2 mRNAs in DRG neurons, NT3 likely contributes to CINP through TrkC-mediated activation of the Ccl2 gene in DRG neurons. NT3 may be thus a potential target for CINP treatment.

Species-level Microbiota of Biting Midges and Ticks from Poyang Lake.

Objective: The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area, namely, Qunlu Practice Base, Peach Blossom Garden, and Huangtong Animal Husbandry, and whether vectors carry any bacterial pathogens that may cause diseases to humans, to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods: Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit (OPU) analysis, we characterized the species-level microbial community structure of two important vector species, biting midges and ticks, including 33 arthropod samples comprising 3,885 individuals, collected around Poyang Lake. Results: A total of 662 OPUs were classified in biting midges, including 195 known species and 373 potentially new species, and 618 OPUs were classified in ticks, including 217 known species and 326 potentially new species. Surprisingly, OPUs with potentially pathogenicity were detected in both arthropod vectors, with 66 known species of biting midges reported to carry potential pathogens, including Asaia lannensis and Rickettsia bellii, compared to 50 in ticks, such as Acinetobacter lwoffii and Staphylococcus sciuri. We found that Proteobacteria was the most dominant group in both midges and ticks. Furthermore, the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria. Pantoea sp7 was predominant in biting midges, while Coxiella sp1 was enriched in ticks. Meanwhile, Coxiella spp., which may be essential for the survival of Haemaphysalis longicornis Neumann, were detected in all tick samples. The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion: Biting midges and ticks carry large numbers of known and potentially novel bacteria, and carry a wide range of potentially pathogenic bacteria, which may pose a risk of infection to humans and animals. The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

The association between intensity-specific physical activity and the number of multiple chronic diseases among Chinese elderly: A study based on the China Health and Retirement Longitudinal study (CHARLS).

Background: With ageing, the elderly are facing a complex situation where multiple chronic diseases coexist. This paper aims to investigate the effect of intensity-specific physical activity on the number of multiple chronic diseases in the elderly. Methods: Our data came from wave 4 of the China Health and Retirement Longitudinal Survey (CHARLS), which involved 10,341 residents aged ≥ 60 years. The intensity-specific physical activity was divided into two categories: moderate-intensity physical activity (MPA) lasting ≥ 150 min/week and vigorous-intensity physical activity (VPA) lasting ≥ 75 min/week. Data on 14 types of chronic diseases were collected. Propensity score matching (PSM) with controlling nine confounding factors were used to analyse the effects of intensity-specific physical activity. Results: Among 10,341 samples, 40.12% of the elderly often participated in MPA and 25.72% participated in VPA. The PSM results showed that performing 150 min/week of MPA leads to 0.0675(P<0.05) fewer multiple chronic diseases than not achieving this standard, and VPA up to 75 min/week leads to 0.0785(P<0.05) fewer multiple chronic disease than that does not meet this criterion. Additionally, VPA is more effective than MPA. Conclusion: Both MPA of at least 150 min/week and VPA of at least 75 min/week can significantly reduce the number of multiple chronic diseases in elderly. Elderly people should increase their exercise intensity as much as possible while ensuring safety.

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain.

BACKGROUND: The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. METHODS: We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. RESULTS: The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. CONCLUSION: Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

Improving the Quality of Laser Drilling by Assisted Process Methods of Static Solution and Mist Blowing.

The use of static solution-assisted laser drilling can effectively improve hole roundness, decrease taper angle, and reduce recast layer thickness and hole wall slag adhesion. However, the enormous energy of the laser will evaporate the solution to form a suspension droplet and reduce the quality and efficiency of laser drilling. To deal with this defect, the mist-blowing method was used to reduce the influence of droplets on the taper angle and recast layer. In this work, the effect of wind speed on drilling quality was examined, and laser drilling in air, water, and NaCl solution was carried out to analyse the effect of solution composition on hole wall morphology. The results showed that a speed fan with a proper wind speed that disperses the droplets formed in the processing area can significantly reduce the refraction and scattering of the laser, and the taper angle and roundness of the drilling hole were also reduced by 15.6% and improved by 2.4%, respectively, under the wind speed of 2 m/s. The hole wall morphology showed a thicker recast layer and cracking in air, while it was thinner in water and there was little or no layer in the NaCl solution in the same current. When drilling in NaCl, the taper angle and roundness of the drilling hole were reduced by 4.13% and improved by 2.11%, respectively, compared to water. Due to the mechanical effect of the laser in the NaCl solution, the impact force on the material was much greater than that in water. The solution cavitation effect, generated by the absorption of laser energy, caused an explosive impact on the molten material adhered to the surface of the hole wall. Above all, drilling in the NaCl solution with a current of 200 A and a wind speed of 2 m/s was the optimal condition for obtaining the best processing quality.