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Detecting and diagnosing neurological diseases in modern healthcare presents substantial challenges that directly impact patient outcomes. The complex nature of these conditions demands precise and quantitative monitoring of disease-associated biomarkers in a continuous, real-time manner. Current chemical sensing strategies exhibit restricted clinical effectiveness due to labor-intensive laboratory analysis prerequisites, dependence on clinician expertise, and prolonged and recurrent interventions. Bio-integrated electronics for chemical sensing is an emerging, multidisciplinary field enabled by rapid advances in electrical engineering, biosensing, materials science, analytical chemistry, and biomedical engineering. This review presents an overview of recent progress in bio-integrated electrochemical sensors, with an emphasis on their relevance to neuroengineering and neuromodulation. It traverses vital neurological biomarkers and explores bio-recognition elements, sensing strategies, transducer designs, and wireless signal transmission methods. The integration of in vivo biochemical sensors is showcased through applications. The review concludes by outlining future trends and advancements in in vivo electrochemical sensing, and highlighting ongoing research and technological innovation, which aims to provide inspiring and practical instructions for future research.

Abstract The visceral organ-brain axis, mediated by vagal sensory neurons, is essential for maintaining various physiological functions. Here, we investigate the impact of liver-projecting vagal sensory neurons on energy balance, hepatic steatosis, and anxiety-like behavior in mice under obesogenic conditions. A small subset of vagal sensory neurons innervate the liver and project centrally to the nucleus of the tractus solitarius, area postrema, and dorsal motor nucleus of the vagus, and peripherally to the periportal areas in the liver. The loss of these neurons prevents diet-induced obesity, and these outcomes are associated with increased energy expenditure. Although males and females exhibit improved glucose homeostasis following disruption of liver-projecting vagal sensory neurons, only male mice display increased insulin sensitivity. Furthermore, the loss of liver-projecting vagal sensory neurons limits the progression of hepatic steatosis. Intriguingly, mice lacking liver-innervating vagal sensory neurons also exhibit less anxiety-like behavior compared to control mice. Modulation of the liver-brain axis may aid in designing effective treatments for both psychiatric and metabolic disorders associated with obesity and MAFLD.

Abstract Background Alzheimer’s disease (AD) is a prevalent neurodegenerative disease (ND). In recent years, multiple clinical and animal studies have shown that mitochondrial dysfunction may be involved in the pathogenesis of AD. In addition, short-chain fatty acids (SCFA) produced by intestinal microbiota metabolism have been considered to be important factors affecting central nervous system (CNS) homeostasis. Among the main mediators of host-microbe interactions, volatile fatty acids play a crucial role. Nevertheless, the influence and pathways of microorganisms and their metabolites on Alzheimer’s disease (AD) remain uncertain. Results In this study, we present distinctions in blood and fecal SCFA levels and microbiota composition between healthy individuals and those diagnosed with AD. We found that AD patients showed a decrease in the abundance of Akkermansia muciniphila and a decrease in propionic acid both in fecal and in blood. In order to further reveal the effects and the mechanisms of propionic acid on AD prevention, we systematically explored the effects of propionic acid administration on AD model mice and cultured hippocampal neuronal cells. Results showed that oral propionate supplementation ameliorated cognitive impairment in AD mice. Propionate downregulated mitochondrial fission protein (DRP1) via G-protein coupled receptor 41 (GPR41) and enhanced PINK1/PARKIN-mediated mitophagy via G-protein coupled receptor 43 (GPR43) in AD pathophysiology which contribute to maintaining mitochondrial homeostasis both in vivo and in vitro. Administered A. muciniphila to AD mice before disease onset showed improved cognition, mitochondrial division and mitophagy in AD mice. Conclusions Taken together, our results demonstrate that A. muciniphila and its metabolite propionate protect against AD-like pathological events in AD mouse models by targeting mitochondrial homeostasis, making them promising therapeutic candidates for the prevention and treatment of AD. Video Abstract

Abstract Background Nephrology referral has been recognized as a modifiable factor influencing patient outcomes. The study aimed to compare clinical outcomes among patients referred early versus late to nephrologists. Methods We searched online database from inception to June 1, 2022, to obtain all eligible literature reporting outcomes of patients referred early versus late to nephrologists. The early and late referral was defined by the time at which patients were referred to nephrologists before dialysis onset. Results Seventy-two studies with over 630,000 patients met the inclusion criteria. A lower likelihood of all-cause mortality (HR = 0.67, 95% CI: 0.62–0.72) was achieved among patients referred early to nephrologists. The survival advantage of early referral was apparent in the first 6 months and extended to the 5th year after dialysis onset (6 months: HR = 0.52, 95% CI: 0.40–0.68; 5 years: HR = 0.67, 95% CI: 0.60–0.74). The early referral was associated with shorter durations of initial hospitalization, a higher rate of kidney transplantation (RR = 1.41, 95% CI: 1.12–1.78), a lower likelihood of emergency start (RR = 0.39, 95% CI: 0.28–0.54), a higher likelihood of permanent access creation (RR = 3.34, 95% CI: 2.43–4.59), increased initial use of permanent access (RR = 2.60, 95% CI: 2.18–3.11), and reduced initial catheter use (RR = 0.43, 95% CI: 0.32–0.58). Conclusions Our study showed a lower risk of mortality, shorter lengths of initial hospitalization, and better preparations for renal replacement therapy among patients referred early to nephrologists. Early nephrology care should be promoted to improve the management of advanced chronic kidney disease.

Abstract Protein citrullination modification plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and anti-citrullinated protein antibodies (ACPAs) are extensively employed for clinical diagnosis of RA. However, there remains limited understanding regarding specific citrullinated proteins and their implications in the progression of RA. In this study, we screen and verify insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) as a novel citrullinated protein with significantly elevated citrullinated level in RA. Autoantibodies against citrullinated IGF2BP1 are further detected in serum and synovial fluid samples from RA patients, which are positively correlated with erythrocyte sedimentation rate (ESR) and disease activity score 28 (DAS28). Transcriptomic sequencing and functional verification show that citrullination at the R167 site of IGF2BP1 promotes the proliferation, migration, and invasion of RA fibroblast-like synoviocytes (RA-FLSs) by improving the mRNA stability of Semaphorin 3D (SEMA3D). Experiments in collagen-induced arthritis (CIA) mice, the classical animal model of RA, show that IGF2BP1 R176K point mutation (Igf2bp1 R167K/R167K) mice exert reduced inflammatory response, clinical scores, and joint destruction. At a molecular level, citrullination of IGF2BP1 promotes the stability of SEMA3D mRNA by promoting the interaction between IGF2BP1 and its cofactor ELAV-like protein 1 (ELAVL1), thereby promoting the invasiveness of RA-FLSs. In this study, a new citrullinated protein of IGF2BP1 is discovered, and the molecular mechanism of its citrullinated modification promoting the progression of RA disease is elucidated, which provides theoretical basis for the diagnosis and treatment of RA.

The pursuit of intelligence and smartness in road infrastructure is critical for the advancement of road engineering. Embedded strain sensors serve as a vital tool for sensing strain within pavement structures. To explore the influence of these embedded strain sensors on the mechanical properties of asphalt mixtures, this study established a mesoscopic model of asphalt mixtures with embedded strain sensors using the discrete element method. The effects of embedment depth and quantity of strain sensors on the mechanical properties of asphalt mixtures were examined, and the impact of the asphalt mixture characteristics (such as nominal maximum particle size, grading, friction coefficient, and asphalt–aggregate bond strength) on the operational performance of the embedded strain sensors was analyzed. The results of the study show that as the embedment depth of the sensors (6 and 4 cm from the bottom of the beam) increases, the horizontal tensile stress at the three monitoring points at the bottom of the beam also increases by 56.9%, 43.5%, and 43.8%. This finding indicates that the closer to the bottom of the beam specimen, the more uniform the distribution of the internal horizontal stress field, which is conducive to the working stability of the sensors. The crack growth rate of the beam specimen embedded with double sensors is faster than that of the beam specimen embedded with a single sensor. When the deflection is 0.8 mm, the number of detected cracks reaches 267 for the double sensors and only 93 for the single sensor. Sensors should not be buried simultaneously in the middle and lower layers of the same point on the pavement. For the asphalt mixtures, large nominal maximum particle sizes (AC-13, AC-16, and AC-20) are associated with few force chains. Compared with that for AC-13, the average force chains for AC-16 and AC-20 are 4.9% and 11.4% lower, respectively, indicating an optimal nominal maximum particle size of 13.2 mm for the mixture. The coarser the grading, the fewer the load transfer paths, resulting in a 77.7% reduction in the number of contact force systems and a decrease in the uniformity of contact force distribution. Furthermore, the maximum contact force increases by 74.6%, leading to the poor operational stability of the sensors. An increase in bond strength (tensile strength and cohesion strength) reduces the maximum contact force by 11%, thereby enhancing the operational stability of the sensors. These outcomes provide a theoretical basis for elucidating the evolution of the service performance of pavement materials with embedded sensing devices.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Abstract Background Nurses serving in infectious disease ward represent a distinct occupational group that has attracted considerable attention following epidemic outbreaks. However, prior to this study, no research had delved into the underlying mechanism linking anxiety to burnout symptoms among infectious disease nurses. This study aimed to explore investigate the association between anxiety and burnout among nurses working in such environments and scrutinized the mediating role of perceived stress and the moderating influence of resilience on the principal relationship. Methods Employing a cross-sectional study using a web-based design, data were collected from 1,579 clinical nurses working in infectious disease ward across 50 hospitals in China. Participants responded to questionnaires assessing anxiety, perceived stress, resilience and burnout. Statistical analyses encompassed descriptive statistics, one-way analyses of variance, independent-samples t-tests, Pearson correlations, and bootstrapping techniques to evaluate the indirect and moderating effects. Results The study revealed that 62.13% of the respondents reported high levels of burnout, and 55.92% experienced moderate to high degrees of emotional exhaustion among infectious disease nurses. Significant correlations were observed between anxiety, perceived stress, resilience, and each component of burnout (P

Abstract Background China has the largest percentage of people with dementia (PwD) around the world. And most of them are cared for by their family members. The purpose of this study was to identify the quality of life (QoL) of family caregivers of PwD in rural China and to investigate the mediating role of social support between caregiver burden and QoL under the guidance of a stress process model. Methods This cross-sectional design study in rural areas of Hunan province, China included 150 family caregivers of PwD. The participants completed questionnaires, including the demographic information questionnaire on caregivers and PwD, the caregiver version of QoL in Alzheimer’s Disease, the Caregiver Burden Inventory, and the Multidimensional Scale of Perceived Social Support. The demographic factors associated with QoL were subjected to univariate analysis. Pearson’s correlations were used to test the relationship among care burden, social support, and QoL. SPSS PROCESS Procedure was conducted to test the hypothesis of mediating effects. Results The family caregivers of PwD exhibited a fair QoL, with a score of 29.01 ± 4.059. Pearson’s correlations revealed the negative correlation of caregiver burden with social support and QoL and the positive correlation between social support and the QoL of family caregivers. The results suggest the mediating role of social support between caregiver burden and the QoL. Conclusion The QoL of family caregivers of PwD in rural China is suboptimal and indirectly influenced by the caregiving burden through the mediating effect of social support. Strengthening social support networks, both formal and informal, is essential to reducing caregiver burden and improving the QoL of family caregivers of PwD.

Abstract Bioenergy with carbon capture and storage (BECCS) is a key negative emission technology for climate mitigation. Some countries have made no commitment to carbon neutrality but are viewed as potential BECCS candidates (hereafter, non-CN countries). Here we analyze contributions of these countries to global climate mitigation with respect to BECCS using an Earth system model with explicit representations of bioenergy crops. Switchgrass cultivation in these non-CN countries can further remove atmospheric CO2 by 9.1 ± 2.8 and 19.9 ± 5.2 PgC in the low-warming and overshot scenarios, resulting in an extra biogeochemical cooling effect of 0.01 ± 0.04 to 0.02 ± 0.06 °C. This cooling is largely counterbalanced by the biophysical warming, but the net effect is still an extra cooling. The non-CN countries play a more important role in the low-warming scenario than in the overshoot scenario, despite the inequality of temperature change among countries. Our study highlights the importance of a global system for climate mitigation.

Abstract This review comprehensively explores the critical role of calcium as an essential small-molecule biomessenger in skeletal muscle function. Calcium is vital for both regulating muscle excitation–contraction coupling and for the development, maintenance, and regeneration of muscle cells. The orchestrated release of calcium from the endoplasmic reticulum (ER) is mediated by receptors such as the ryanodine receptor (RYR) and inositol 1,4,5-trisphosphate receptor (IP3R), which is crucial for skeletal muscle contraction. The sarcoendoplasmic reticulum calcium ATPase (SERCA) pump plays a key role in recapturing calcium, enabling the muscle to return to a relaxed state. A pivotal aspect of calcium homeostasis involves the dynamic interaction between mitochondria and the ER. This interaction includes local calcium signaling facilitated by RYRs and a “quasi-synaptic” mechanism formed by the IP3R-Grp75-VDAC/MCU axis, allowing rapid calcium uptake by mitochondria with minimal interference at the cytoplasmic level. Disruption of calcium transport can lead to mitochondrial calcium overload, triggering the opening of the mitochondrial permeability transition pore and subsequent release of reactive oxygen species and cytochrome C, ultimately resulting in muscle damage and atrophy. This review explores the complex relationship between the ER and mitochondria and how these organelles regulate calcium levels in skeletal muscle, aiming to provide valuable perspectives for future research on the pathogenesis of muscle diseases and the development of prevention strategies.

Abstract Background FFPE tissue samples are commonly used in biomedical research and are a valuable source for next-generation sequencing in oncology, however, extracting RNA from these samples can be difficult the quantity and quality achieved can impact the downstream analysis. This study compared the effectiveness of seven different commercially available RNA extraction kits specifically designed for use with FFPE samples in terms of the quantity and quality of RNA recovered. Methods This study used 9 samples of FFPE tissue from three different types of tissue (Tonsil, Appendix and lymph node of B-cell lymphoma) to evaluate RNA extraction methods. Three sections of 20 µm of each sample were combined per sample. The slices were distributed in a systematic manner to prevent any biases. Each of the 7 commercially available RNA extraction kits were used according to manufacturer's instructions, with each sample being tested in triplicate resulting in a total of 189 extractions. The concentration, RNA quality score (RQS) and DV200 of each extraction was analysed using a nucleic acid analyser to determine the quantity and quality of the recovered RNA. Results This study found that despite processing the FFPE samples in the same standardized way, there were disparities in the quantity and quality of RNA recovered across the different tissue types. Additionally, the study found notable differences in the quantity of RNA recovered when using different extraction kits. In terms of quality, three of the kits performed better than the other four in terms of RQS and DV200 values. Conclusion Though many laboratories have developed their own protocols for specific tissue types, using commercially available kits is still a popular option. Although these kits use similar processes and extraction procedures, the amount and quality of RNA obtained can vary greatly between kits. In this study, among the kits tested, while the Roche kit, provided a nearly systematic better-quality recovery than other kits, the ReliaPrep FFPE Total RNA miniprep from Promega yielded the best ratio of both quantity and quality on the tested tissue samples.

Introduction: Cardiac fibrosis is the main driver for adverse remodeling and progressive functional decline in nearly all types of heart disease including myocardial infarction (MI). The activation of cardiac fibroblasts (CF) into myofibroblasts is responsible for cardiac fibrosis. Unfortunately, no ideal approach for controlling CF activation currently exists. Objectives: This study investigated the role of Heat shock protein A12A (HSPA12A), an atypical member of the HSP70 family, in CF activation and MI-induced cardiac fibrosis. Methods: Primary CF and Hspa12a knockout mice were used in the experiments. CF activation was indicated by the upregulation of myofibroblast characters including alpha-Smooth muscle actin (αSMA), Collagen, and Fibronectin. Cardiac fibrosis was illustrated by Masson’s trichrome and picrosirius staining. Cardiac function was examined using echocardiography. Glycolytic activity was indicated by levels of extracellular lactate and the related protein expression. Protein stability was examined following cycloheximide and MG132 treatment. Protein-protein interaction was examined by immunoprecipitation-immunoblotting analysis. Results: HSPA12A displayed a high expression level in quiescent CF but showed a decreased expression in activated CF, while ablation of HSPA12A in mice promoted CF activation and cardiac fibrosis following MI. HSPA12A overexpression inhibited the activation of primary CF through inhibiting glycolysis, while HSPA12A knockdown showed the opposite effects. Moreover, HSPA12A upregulated the protein expression of transcription factor p53, by which mediated the HSPA12A-induced inhibition of glycolysis and CF activation. Mechanistically, this action of HSPA12A was achieved by acting as a scaffolding protein to bind p53 and ubiquitin specific protease 10 (USP10), thereby promoting the USP10-mediated p53 protein stability and the p53-medicated glycolysis inhibition. Conclusion: The present study provided clear evidence that HSPA12A is a novel endogenous inhibitor of CF activation and cardiac fibrosis. Targeting HSPA12A in CF could represent a promising strategy for the management of cardiac fibrosis in patients.

In this study, a hybrid additive manufacturing (AM) process that combines interlayer friction stir processing (FSP) with wire arc additive manufacturing (WAAM) is proposed to address the problems of high porosity, coarse grains, and low mechanical properties encountered in WAAM Al alloys. Straight walls of Al–Cu alloy were prepared using Er2319 wire and interlayer FSP was conducted to tailor the microstructure of deposited layers. The effects of interlayer FSP on the microstructure and mechanical properties of WAAM Al–Cu alloy was analyzed. Results show that the pore characteristics vary at different regions on the cross-section of the deposited walls. The interlayer FSP can partially repair pores by violent stirring action and downward force from FSP tool, and thereby decreases the pore size, pore density and pore area fraction of the WAAM Al–Cu alloy. Additionally, the interlayer FSP can significantly refine grains, resulting in a wider fine grain region in the WAAM-FSP sample. The WAAM-FSP samples have a larger number density of spot-like particles as compared to the WAAM samples due to the fragmentation as well as partially dissolution of second-phase particles caused by the violent stirring action and intense deformation of FSP. Both strengths and elongations of the manufactured Al–Cu alloy are enhanced by interlayer FSP, which is mainly ascribed to the combined action of porosity reduction, grain refinement, fragmentation and dissolution of the second-phase particles caused by interlayer FSP. The present study can provide theoretical guidance for the fabrication of Al-based alloy components with high performance using hybrid WAAM-FSP technique.

Objective: Mume fructus is commonly used in traditional Chinese medicine to treat nocturnal asthma symptoms. However, the molecular mechanisms underlying its effects on nocturnal asthma have not yet been established. This study evaluated the therapeutic mechanisms of Mume fructus in treating nocturnal asthma. Materials and Methods: Network pharmacology was used to investigate the chemical composition, critical targets, and potential mechanisms of action of Mume fructus in treating nocturnal asthma. “Mume fructus” and “nocturnal asthma” were used as keywords to search the relevant databases. The 16HBE and RAW264.7 cells were treated with various concentrations of Mume fructus and lipopolysaccharides (LPSs). Data provided included analyses of cell viability detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, cell proliferation and apoptosis detected by 5-ethynyl-2’-deoxyuridine and Hoechst 33342, messenger ribonucleic acid (mRNA) levels obtained by real-time polymerase chain reaction, and protein expression detected by Western blotting. Additionally, immunofluorescence was used to detect nuclear translocation. Results: Network pharmacology analyses were mainly enriched in nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) pathway, and interleukin (IL)-6. Mume fructus and LPS had no effect on viability, proliferation, and apoptosis in 16HBE and RAW264.7 cells under certain concentration conditions. Mume fructus counteracted LPS-stimulated mRNA and protein expression of IL-6. In addition, Mume fructus treatment prevented the LPS-induced phosphorylation of NF-κB and MAPK pathways, as well as the nuclear translocation of NF-κB p-p65 in the 16HBE and RAW264.7 cells. Conclusions: Mume fructus can treat nocturnal asthma by regulating the NF-κB and MAPK pathways and counteracting IL-6 expression. These findings provide a scientific basis for the use of Mume fructus in the treatment of nocturnal asthma.

Abstract DSG2, encoding desmoglein-2, is one of the causative genes of arrhythmogenic cardiomyopathy. We previously identified a homozygous DSG2 p.Arg119Ter stop-gain variant in a patient with juvenile-onset cardiomyopathy and advanced biventricular heart failure. However, the pathological significance and prevalence of the heterozygous DSG2 p.Arg119Ter variant remains uncertain. Here, we identified four unrelated patients with cardiomyopathy with heterozygous DSG2 p.Arg119Ter variants among 808 patients with nonischemic cardiomyopathy; the allele frequency was 0.0037, which is more than 50-fold greater than that reported in the general Japanese population. These patients were clinically diagnosed with arrhythmogenic right ventricular cardiomyopathy (Pt-1), dilated cardiomyopathy (DCM) after ventricular septum defect closure surgery (Pt-2), DCM (Pt-3), and end-stage hypertrophic cardiomyopathy (Pt-4). The patients also exhibited reduced left ventricular contractile function and varying clinical courses. Genetic analysis identified additional possible causative variants, DSG2 p.Arg292Cys in Pt-1 and BAG3 p.His166SerfsTer6 in Pt-3. Immunohistochemical analysis of endomyocardial biopsy samples revealed that the expression of not only desmoglein-2 but also desmoplakin was markedly reduced. Transmission electron microscopy revealed pale and fragmented desmosomes and widened gaps between intercalated discs in the myocardium. A microforce test using human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs) demonstrated reduced contractility in iPSC-CMs carrying a heterozygous truncating variant in DSG2. These data suggest that the DSG2 p.Arg119Ter variant is concealed in patients with cardiomyopathy with heart failure, and desmosome impairment may be a latent exacerbating factor of contractile dysfunction and disease progression.