Metabolic Syndrome and Risk of Amyotrophic Lateral Sclerosis: Insights from a Large-Scale Prospective Study.

OBJECTIVE: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS. METHODS: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms. RESULTS: In this study, a total of 539 cases of ALS were recorded after a median follow-up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19-1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19-1.95; HR: 1.31, 95% CI: 1.06-1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ-glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega-6 fatty acids to omega-3 fatty acids ratio. INTERPRETATION: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024.

How inflammation dictates diabetic peripheral neuropathy: An enlightening review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. AIMS: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. METHODS: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. RESULTS: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. CONCLUSIONS: This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.

Vitamin D and diabetic peripheral neuropathy: A multi-centre nerve conduction study among Chinese patients with type 2 diabetes.

AIMS: Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is scarce. The present multi-centre study sought to investigate these associations based on objective quantifications. MATERIALS AND METHODS: Information on DPN-related symptoms, signs, all diabetic microvascular complications, and nerve conduction abilities (quantified by nerve conduction amplitude and velocity, F-wave minimum latency (FML) of peripheral nerves) were collected from a derivation cohort of 1192 patients with type 2 diabetes (T2D). Correlation, regression analysis, and restricted cubic splines (RCS) were used to explore linear and non-linear relationships between vitamin D and DPN, which were validated in an external cohort of 223 patients. RESULTS: Patients with DPN showed lower levels of vitamin D than those without DPN; patients with vitamin D deficiency (<30 nmol/L) tended to suffer more DPN-related neurological deficits (paraesthesia, prickling, abnormal temperature, ankle hyporeflexia, and distal pall hypoesthesia correlating with MNSI-exam score (Y = -0.005306X + 2.105, P = 0.048). Worse nerve conduction abilities (decreased motor nerve amplitude, sensory nerve amplitude, motor nerve velocity, and increased FML) were also observed in these patients. Vitamin D had a significant threshold association with DPN (adjusted OR = 4.136, P = 0.003; RCS P for non-linearity = 0.003) and correlates with other microvascular complications (diabetic retinopathy and diabetic nephropathy). CONCLUSIONS: Vitamin D is associated with the conduction ability of peripheral nerves and may have a nerve- and threshold-selective relationship with the prevalence and severity of DPN among patients with T2D.

Neuron-specific enolase in hypertension patients with acute ischemic stroke and its value forecasting long-term functional outcomes.

BACKGROUND: Neuron Specific Enolase (NSE), a neuro-biochemical protein marker, may correlate with the prognosis of stroke patients. Moreover, hypertension is the most common comorbidities in patients with acute ischemic stroke (AIS), and the relationship between NSE levels and long-term functional outcomes in such an increasingly large population is unclear. The aim of the study was to investigate the relationships mentioned above and optimize the prediction models. METHODS: From 2018 to 2020, 1086 admissions for AIS were grouped as hypertension and non-hypertension, while hypertension group was randomly divided into development and validation cohorts for internal validation. The severity of the stroke was staged by National Institutes of Health Stroke Scale (NIHSS) score. Stroke prognosis after 1 year of follow up was documented by modified Rankin Scale (mRS) score. RESULTS: Analysis revealed the following findings:(i) Serum NSE levels increased greatly in hypertension subjects with poor functional outcomes(p = 0.046). However, there was no association in non-hypertension individuals(p = 0.386). (ii) In addition to the conventional factors (age and NIHSS score), NSE (OR:1.241, 95% CI: 1.025-1.502) and prothrombin time were significantly related to the incidence of unfavorable outcomes. (iii)Based on the above four indicators, a novel nomogram was established to predict the prognosis of stoke in hypertension patients with the c-index values of 0.8851. CONCLUSIONS: Overall, high baseline NSE is associated with poor 1-year AIS outcomes in hypertension patients, suggesting NSE may be a potential prognostic and therapeutic target for stroke in hypertension patients.

Liver function parameters aspartate aminotransferase and total protein predict functional outcome in stroke patients with non-cardioembolism.

Stroke, classified as cardioembolism and non-cardioembolism (non-CE), entails a large socioeconomic burden on the elderly. The morbidity and mortality of non-CE are high, whereas studies concerning prognostic factors impacting function outcome remain underdeveloped and understudied. Liver function parameters are convenient approaches to predicting prognosis in cardiovascular diseases, but their clinical significance has not been well characterized in stroke, especially in non-CE. In our study, a total of 576 patients with non-CE at 1 year of follow-up were enrolled in a cohort from a consecutive hospital-based stroke registry, with randomly 387 patients as the development cohort and 189 patients as the validation cohort. The univariate and multivariate analyses revealed the following novel findings: (i) The incidence of unfavorable functional outcomes after non-CE was significantly greater (p < 0.01) in patients with higher age, aspartate aminotransferase (AST), the National Institutes of Health Stroke Scale (NIHSS) score, and depressed total protein (TP); (ii) We established a novel model and nomogram to predict stroke prognosis, in addition to the known factors (age and the NIHSS score). The levels of AST and TP were independently correlated with the incidence of unfavorable outcomes [AST: odds ratio (OR) = 1.026, 95% CI (1.002-1.050); TP: OR = 0.944, 95% CI (0.899-0.991)]; (iii) The results persisted in further subgroup analysis stratified by age, gender, the NIHSS score, and other prespecified factors, especially in males 60 years or older. Overall, this study demonstrates that hepatic parameters (AST and TP) after non-CE are considered to be associated with functional outcomes at 1-year follow-up, especially in males aged ≥ 60 years.

Low T3 syndrome is associated with peripheral neuropathy in patients with type 2 diabetes mellitus.

INTRODUCTION/AIMS: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. Diabetic patients often have thyroid dysfunction. The aim of this study was to investigate the association between low triiodothyronine (T3) syndrome and DPN in patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective review was performed of 928 patients with T2DM for whom data was available for clinical manifestations and nerve conduction studies (NCS), and of 134 non-diabetic controls. The composite Z scores of conduction velocity and amplitude were calculated. Low T3 syndrome was defined as T3 levels below the lower limit of the reference interval. RESULTS: Among the patients with T2DM, 632 (68.1%) had DPN, and a larger proportion of these patients presented with low T3 syndrome than patients without DPN. After adjusting for potential confounders, low T3 syndrome was independently associated with the occurrence of DPN (odds ratio [OR] = 2.049, 95% confidence interval [CI] 1.319-3.181, p = .001) and the severity of DPN (OR = 1.597, 95% CI 1.030-2.476, p = .036). Adding the criterion of low T3 syndrome improved the prognostic performance of the traditional model (age + gender + diabetic duration + glycated hemoglobin [HbA1c]) for predicting DPN. DISCUSSION: Low T3 syndrome is associated with a higher risk and increased severity of DPN in patients with T2DM. These findings suggest that low T3 syndrome could be a predictor for risk stratification in patients with T2DM.

Janus Fibrous Mats Based Suspended Type Evaporator for Salt Resistant Solar Desalination and Salt Recovery.

Solar desalination has been recognized as an emerging strategy for solving the pressing global freshwater crisis. However, salt crystallization at the photothermal interface frequently causes evaporator failure. In addition, arbitrary discharge of concentrated brine produced during desalination results in potential ecological impacts as well as wastage of valuable minerals. In the present work, a suspended-type evaporator (STEs) constructed using Janus fibrous mats is reported. The fibrous structure wicks brine to the evaporation layer and the salt gets confined in the evaporation layer until crystallization for zero liquid discharge due to the suspended design. Enhanced evaporation is observed because STEs have an additional low-resistance vapor escape path directly from the evaporation layer to the atmosphere compared to traditional floating Janus evaporators. Moreover, owing to the drastically different wettability on both sides, the evaporator allows salt crystallization only on the hydrophilic bottom layer, thus eliminating salt accumulation at the hydrophobic photothermal interface. With this unique structural design, the proposed evaporator not only maintains a high evaporation rate of 1.94 kg m-2 h-1 , but also demonstrates zero liquid discharged salt resistance and ideal recovery of the mineral in brine.

Microwave irradiation directly excites semiconductor catalyst to produce electric current or electron-holes pairs.

Generally, photon of Microwave (MW) electromagnetic waves have long been thought to be lower energy, which could not excite metals or semiconductor materials to generate electric current and electron-holes pairs (e-cb + h+vb). In this paper, we report an unexpected, Microwave "photoelectric effect", when MW irradiates on the semiconductor materials, leading to generate electric current and electron-holes pairs (e-cb + h+vb), on the semiconductor materials and on the MW catalyst. Further, we show that the action mechanism of Microwave "photoelectric effect" made water adsorbing on the surface of Microwave catalyst transform into hydroxyl radical (∙OH). Thus, this study has revealed the principle of generation Microwave "photoelectric effect" under MW irradiation, and the mechanism of MW catalytic oxidation degradation of organic in the wastewater and the mechanism of MW reduction method for preparation of nano-particle metal supported catalysts. Our findings challenge the classic view of MW irradiation only as heating method, which cannot excite to produce electric current and electron-holes pairs (e-cb + h+vb). Our findings will open new field to use MW technology for MW catalytic oxidation degradation of organics in the wastewater, and for MW reduction method of metal supported catalysts preparation.

Spectrum-Effect Relationships Between the Bioactive Ingredient of Syringa oblata Lindl. Leaves and Its Role in Inhibiting the Biofilm Formation of Streptococcus suis.

Syringa oblata Lindl. (S. oblata) has been used in herbal medicines for treating bacterial diseases. It is also thought to inhibit Streptococcus suis (S. suis) biofilm formation. However, due to the inherent nature of the complexity in its chemical properties, it is difficult to understand the possible bioactive ingredients of S. oblata. The spectrum-effect relationships method was applied to screen the main active ingredients in S. oblata obtained from Heilongjiang Province based on gray relational analysis. The results revealed that Sub-MICs obtained from 10 batches of S. oblata could inhibit biofilm formation by S. suis. Gray relational analysis revealed variations in the contents of 15 main peaks and rutin was discovered to be the main active ingredient. Then, the function of rutin was further verified by inhibiting S. suis biofilm formation using crystal violet staining. Computational studies revealed that rutin may target the chloramphenicol acetyltransferase protein in the biofilm formation of S. suis. In conclusion, this study revealed that the spectrum-effect relationships and computational studies are useful tools to associate the active ingredient with the potential anti-biofilm effects of S. oblata. Here, our findings would provide foundation for the further understanding of the mechanism of S. oblata intervention in biofilm formation.

Rutin Inhibits Streptococcus suis Biofilm Formation by Affecting CPS Biosynthesis.

Streptococcus suis (S. suis) form biofilms and causes severe diseases in humans and pigs. Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances. Eradicating biofilms with the use of antibiotics or biocides is often ineffective and needs replacement with other potential agents. Compared to conventional agents, promising and potential alternatives are biofilm-inhibiting compounds without impairing growth. Here, we screened a S. suis adhesion inhibitor, rutin, derived from Syringa. Rutin, a kind of flavonoids, shows efficient biofilm inhibition of S. suis without impairing its growth. Capsular polysaccharides(CPS) are reported to be involved in its adherence to influence bacterial biofilm formation. We investigated the effect of rutin on S. suis CPS content and structure. The results showed that rutin was beneficial to improve the CPS content of S. suis without changing its structure. We further provided evidence that rutin specifically affected S. suis biofilm susceptibility by affecting CPS biosynthesis in vitro. The study explores the antibiofilm potential of rutin against S. suis which can be used as an adhesion inhibitor for the prevention of S. suis biofilm-related infections. Nevertheless, rutin could be used as a novel natural inhibitor of biolfilm and its molecular mechanism provide basis for its pharmacological and clinical applications.

Syringa oblata Lindl. Aqueous Extract Is a Potential Biofilm Inhibitor in S. suis.

Streptococcus suis (S. suis) is a zoonotic pathogen that causes severe disease symptoms in pigs and humans. Syringa oblata Lindl. distributed in the middle latitudes of Eurasia and North America were proved as the most development potential of Chinese Medicine. In this study, biofilm formation by S. suis decreased after growth with 1/2 MIC, 1/4 MIC, or 1/8 MIC of Syringa oblata Lindl. aqueous extract and rutin. Scanning electron microscopy analysis revealed the potential effect of Syringa oblata Lindl. aqueous extract and rutin against biofilm formation by S. suis. Using iTRAQ technology, comparative proteomic analyses was performed at two conditions: 1/2 MIC of Syringa oblata Lindl. aqueous extract treated and non-treated cells. The results revealed the existence of 28 proteins of varying amounts. We found that the majority of the proteins were related to cell growth and metabolism. We also found that Syringa oblata Lindl. Aqueous extract affected the synthesis enzymes. In summary, Syringa oblata Lindl. aqueous extract might be used to inhibit the biofilm formation effectively by S. suis, and the active ingredients of the Syringa oblate Lindl. aqueous extract is rutin. The content of rutin is 9.9 ± 0.089 mg/g dry weight.

A new type of power energy for accelerating chemical reactions: the nature of a microwave-driving force for accelerating chemical reactions.

The use of microwave (MW) irradiation to increase the rate of chemical reactions has attracted much attention recently in nearly all fields of chemistry due to substantial enhancements in reaction rates. However, the intrinsic nature of the effects of MW irradiation on chemical reactions remains unclear. Herein, the highly effective conversion of NO and decomposition of H2S via MW catalysis were investigated. The temperature was decreased by several hundred degrees centigrade. Moreover, the apparent activation energy (Ea') decreased substantially under MW irradiation. Importantly, for the first time, a model of the interactions between microwave electromagnetic waves and molecules is proposed to elucidate the intrinsic reason for the reduction in the Ea' under MW irradiation, and a formula for the quantitative estimation of the decrease in the Ea' was determined. MW irradiation energy was partially transformed to reduce the Ea', and MW irradiation is a new type of power energy for speeding up chemical reactions. The effect of MW irradiation on chemical reactions was determined. Our findings challenge both the classical view of MW irradiation as only a heating method and the controversial MW non-thermal effect and open a promising avenue for the development of novel MW catalytic reaction technology.

Highly efficient degradation of 4-nitrophenol over the catalyst of Mn2O3/AC by microwave catalytic oxidation degradation method.

A new microwave catalytic oxidation process based on two kinds of catalysts, the commercially available activated carbon (AC) and Mn2O3 nanoparticle modified AC (Mn2O3/AC), was reported for the degradation of 4-nitrophenol (4-NP) without adding any oxidant. Effects of microwave power, catalyst dosage, irradiation time, and initial concentration for the degradation efficiency were studied. Results indicated that catalyst of Mn2O3/AC showed much higher catalytic activity than pure AC and Mn2O3 particles. Significantly, 4-NP degradation efficiency reached 99.6%, corresponding to 93.5% TOC removal under optimal conditions with microwave power of 400W, Mn2O3/AC dosage of 2g, reaction time of 5min, and initial concentration of 100mg/L. Hydroxyl radicals (OH) generated during catalytic reaction is the main oxidant, and O2 can not effectively improve removal rate. We proposed the microwave 'photoelectric effect' to interpret the generation of OH in view that microwave irradiation can directly excite the catalyst to produce electron-hole pairs and then transform H2O into OH on the surface of catalyst in solution. The obtained kinetic equation for microwave catalytic oxidation degradation of 4-NP was in line with pseudo-first-order kinetic model, that is, apparent rate constant increased as microwave power density increase.