Ultrahighly Sensitive and Selective Glutathione Sensor Based on Carbon Dot-Functionalized Solution-Gate Graphene Transistor.

A new type of carbon dot (CD)-functionalized solution-gated graphene transistor (SGGT) sensor was designed and fabricated for the highly sensitive and highly selective detection of glutathione (GSH). The CDs were synthesized via a one-step hydrothermal method using DL-thioctic acid and triethylenetetramine (TETA) as sources of S, N, and C. The CDs have abundant amino and carboxyl groups and were used to modify the surface of the gate electrode of SGGT as probes for detecting GSH. Remarkably, the CDs-SGGT sensor exhibited excellent selectivity and ultrahigh sensitivity to GSH, with an ultralow limit of detection (LOD) of up to 10-19 M. To the best of our knowledge, the sensor outperforms previously reported systems. Moreover, the CDs-SGGT sensor shows rapid detection and good stability. More importantly, the detection of GSH in artificial serum samples was successfully demonstrated.

[Pathogenesis of Psoriatic Pruritus].

Pruritus is a common symptom of most primary skin diseases and some systemic diseases. Despite the high incidence of pruritus in patients with psoriasis,the specific pathogenesis is complex and unclear. The occurrence and development of skin pruritus in psoriasis patients involve the joint participation of nervous,immune,endocrine,and vascular systems.This article reviews the mediators related to the pathogenesis of pruritus in psoriasis,aiming to improve the understanding of itching symptoms and the treatment of pruritus.

Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives.

The hypothalamic-pituitary-adrenal (HPA) axis is a critical component of the neuroendocrine system, playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus, hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis. This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture. Please cite this article as: Zheng JY, Zhu J, Wang Y, Tian ZZ. Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives. J Integr Med. 2024; 22(4): 446-459.

Electroacupuncture negatively regulates the Nesfatin-1/ERK/CREB pathway to alleviate HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma.

BACKGROUND: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis constitutes a pivotal response by surgical trauma, manifesting as a critical aspect of the acute stress reaction. This hyperactivity resulted in adverse surgical outcomes and is often associated with increased postoperative anxiety. Increased evidence suggests that Nesfatin-1 plays a crucial role in stress responses and stress-related psychiatric disorders. Electroacupuncture (EA) is widely used to alleviate stress responses and anxiety, although its mechanism of action remains unclear. This study aimed to assess the mechanisms by which hypothalamic Nesfatin-1 contribute to the alleviation of HPA axis hyperactivity and anxiety by EA. METHODS: Partial hepatectomy (HT) was performed to simulate surgical trauma, and EA was applied at Zusanli (ST36) and Sanyinjiao (SP6). The levels of hypothalamic Nesfatin-1, c-Fos, and corticotropin-releasing hormone (CRH) were detected, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were regarded as indicators of HPA axis activity. Anxiety levels were assessed through open field tests (OFT), elevated plus maze (EPM), and light-dark box tests (LDBT). To investigate the role of Nesfatin-1, its expression was modulated using stereotactic viral injections or plasmid transfections. Transcriptome sequencing was employed to explore the downstream signaling pathways of Nesfatin-1. Additionally, brain cannula implantation was performed to facilitate targeted drug administration. RESULTS: Our findings demonstrated that EA reduced the hypothalamic overexpression of CRH and Nesfatin-1, as well as serum levels of ACTH and CORT. Additionally, it alleviated anxiety-like behaviors resulting from surgical trauma. We observed that overexpression of Nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) triggered hyperactivity of the HPA axis and anxiety. Conversely, knocking down Nesfatin-1 in the PVN reversed these effects caused by surgical trauma. Transcriptome sequencing identified the extracellular regulated protein kinases (ERK)/cAMP-response element binding protein (CREB) pathway as a key mediator in the impacts of surgical trauma and EA on the hypothalamus. Both in vivo and in vitro studies showed that overexpression of Nesfatin-1 activated the ERK/CREB pathway. Furthermore, administering ERK or CREB inhibitors into the PVN mitigated HPA axis hyperactivity and anxiety-like behaviors induced by surgical trauma. Finally, EA was observed to decrease the phosphorylation levels of ERK and CREB in the PVN. CONCLUSION: EA alleviates HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma through inhibition of Nesfatin-1/ERK/CREB pathway in the hypothalamus.

Constraint-Induced Movement Therapy Modulates Neuron Recruitment and Neurotransmission Homeostasis of the Contralesional Cortex to Enhance Function Recovery after Ischemic Stroke.

Stroke often results in long-term and severe limb dysfunction for a majority of patients, significantly limiting their activities and social participation. Constraint-induced movement therapy (CIMT) is a rehabilitation approach aimed explicitly at enhancing upper limb motor function following a stroke. However, the precise mechanism remains unknown. This study explores how CIMT may alleviate forelimb paralysis in ischemic mice, potentially through structural and functional remodeling of brain regions beyond the infarct area, especially the contralateral cortex. We demonstrated that CIMT recruits neurons from the contralesional cortex into the network that innervates the affected forelimb, as evidenced by PRV retrograde nerve tracing. Additionally, we investigated how CIMT influences synaptic plasticity in the contralateral cortex by evaluating synaptic growth marker levels and neurotransmission's homeostatic regulation. Our findings uncover a rehabilitative mechanism by which CIMT treats ischemic stroke, characterized by increased recruitment of neurons from the contralateral cortex into the network that innervates the affected forelimb, facilitated by homeostatic regulation of neurotransmission.

Differential diagnostic value of radiomics models in benign versus malignant vertebral compression fractures: A systematic review and meta-analysis.

PURPOSE: Early diagnosis of benign and malignant vertebral compression fractures by analyzing imaging data is crucial to guide treatment and assess prognosis, and the development of radiomics made it an alternative option to biopsy examination. This systematic review and meta-analysis was conducted with the purpose of quantifying the diagnostic efficacy of radiomics models in distinguishing between benign and malignant vertebral compression fractures. METHODS: Searching on PubMed, Embase, Web of Science and Cochrane Library was conducted to identify eligible studies published before September 23, 2023. After evaluating for methodological quality and risk of bias using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), we selected studies providing confusion matrix results to be included in random-effects meta-analysis. RESULTS: A total of sixteen articles, involving 1,519 vertebrae with pathological-diagnosed tumor infiltration, were included in our meta-analysis. The combined sensitivity and specificity of the top-performing models were 0.92 (95 % CI: 0.87-0.96) and 0.93 (95 % CI: 0.88-0.96), respectively. Their AUC was 0.97 (95 % CI: 0.96-0.99). By contrast, radiologists' combined sensitivity was 0.90 (95 %CI: 0.75-0.97) and specificity was 0.92 (95 %CI: 0.67-0.98). The AUC was 0.96 (95 %CI: 0.94-0.97). Subsequent subgroup analysis and sensitivity test suggested that part of the heterogeneity might be explained by differences in imaging modality, segmentation, deep learning and cross-validation. CONCLUSION: We found remarkable diagnosis potential in correctly distinguishing vertebral compression fractures in complex clinical contexts. However, the published radiomics models still have a great heterogeneity, and more large-scale clinical trials are essential to validate their generalizability.

Abundant small microplastics hidden in water columns of the Yellow Sea and East China Sea: Distribution, transportation and potential risk.

Microplastics (MPs) pose significant concerns for marine ecological security due to their minuteness and ubiquity. However, comprehensive knowledge on their distribution and fate in seawater columns remains limited. This study investigated the abundances and characteristics of MPs across 3-6 water layers in the South Yellow Sea and East China Sea. Results indicate that high-abundance small MPs (< 100 µm) (average 6567 items/m3) were hidden beneath the sea-surface, predominantly fine-grained particles (< 20 µm) and high-density polymers (> 1.03 g/cm3). The total suspended MPs (5.0-834.2 µm) are estimated at 2.9-3.1 × 1017 particles, with most of them occurring in upper layers. In profiles, their distribution varied by physical properties with depth; fragment-shaped and high-density MPs increased in proportion at greater depths, contrasting with fibrous MPs. These MPs originated primarily from the Yangtze River and their winter transport was driven by the Yangtze River Dilution Water, East China Sea Coastal Current, and Yellow Sea Warm Current, resulting in their accumulation in coastal and estuarine regions. Consequently, the Yangtze River Estuary ecosystem faces substantial risks from MP pollution throughout the water column. This work unveils the prevalence of small MPs in coastal water columns and intricate interaction between their fate and hydrodynamic conditions.

Microplastics in remote coral reef environments of the Xisha Islands in the South China Sea: Source, accumulation and potential risk.

Microplastics (MPs) are of great concern to coral health, particularly enhanced biotoxicity of small microplastics (< 100 µm) (SMPs). However, their fate and harm to remote coral reef ecosystems remain poorly elucidated. This work systematically investigated the distributions and features of MPs and SMPs in sediments from 13 islands/reefs of the Xisha Islands, the South China Sea for comprehensively deciphering their accumulation, sources and risk to coral reef ecosystems. The results show that both MPs (average, 682 items/kg) and SMPs (average, 375 items/kg) exhibit heterogeneous distributions, with accumulation within atolls and dispersion across fringing islands, which controlled by human activities and hydrodynamic conditions. Cluster analysis for the first time reveals a pronounced difference in their compositions between the southern and northern Xisha Islands and resultant distinct sources, i.e., MPs in the north part were leaked mainly from local domestic sewage and fishing waste, while in the south part were probably derived from industrial effluents from adjacent countries. Our ecological risk assessment suggests that the ecosystem within the Yongle Atoll is exposed to a high-risk of MPs pollution. The novel results and proposed framework facilitate to effectively manage and control MPs and accordingly preserve a fragile biosphere in remote coral reefs.

Role of brain NUCB2/nesfatin-1 in stress and stress-related gastrointestinal disorders.

Since the discovery of NUCB2/nesfatin-1 as a novel anorexigenic factor, the expanding function of this peptide has been elucidated in recent years. Increasing evidence suggests that NUCB2/nesfatin-1 is also involved in the regulation of stress and stress-related gastrointestinal disorders. Therefore, we investigated the relationship between NUCB2/nesfatin-1, stress and stress-related gastrointestinal disorders and summarized the results of these studies. Different stressors and duration of stress activate different NUCB2/nesfatin-1-associated brain regions and have different effects on serum corticosterone levels. Central and peripheral NUCB2/nesfatin-1 mediates stress-related gastrointestinal disorders but appears to be protective against inflammatory bowel disease. NUCB2/nesfatin-1 plays an important role in mediating the brain-gut crosstalk, but precise clarification is still needed to gain more insight into these complex relationships.

Electroacupuncture alleviates perioperative hypothalamus-pituitary-adrenal axis dysfunction via circRNA-miRNA-mRNA networks.

Electroacupuncture (EA) has long been used to alleviate surgery-induced hypothalamic-pituitary-adrenal axis dysfunction. However, its downstream gene targets in the brain remain unclear. The aim of the present study was to clarify the potential targets of EA based on RNA sequencing techniques (RNA-seq). Rats were divided into normal control (NC), hepatectomy surgery (HT), HT + EA, and HT + sham EA groups followed by RNA-seq of two representative nuclei in the hypothalamus and amygdala. Weighted Gene Co-expression Network Analysis and Gene Set Enrichment Analysis identified six gene modules associated with neuroendocrine transmitters and neural remodeling in the hypothalamus. Furthermore, circRNA-miRNA-mRNA interaction networks revealed EA-related candidate miRNAs and circRNAs, of which opioid receptor mu 1 might be an EA-specific target, and showed regulation by competing endogenous RNA. We identified the neuroendocrine circRNA-miRNA-mRNA networks through which EA has an effect on HPA axis dysfunction, thus providing potential targets and future research directions for EA treatment.

Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the prognostic factors for mortality in bullous pemphigoid. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were searched to collect literature on the prognostic factors for mortality in bullous pemphigoid. The quality of studies was assessed by Newcastle-Ottawa Quality Assessment Scale. Two researchers extracted relevant data and scored study quality independently. The hazard ratio (HR) was calculated using the random effects model. Study heterogeneity was assessed using both Cochran's Q test and I2 statistics. The causes of heterogeneity were assessed by subgroup analysis and/ or sensitivity analysis when heterogeneity was significant. When ten or more studies were included as outcome indicators, publication bias was evaluated by funnel plot and Egger's test. RESULTS: Out of a total of 1,546 articles retrieved, 15 studies involving 2,435 patients were included. The meta-analysis showed that the mortality of patients with bullous pemphigoid increased with positive bullous pemphigoid 180 antibody (HR = 1.85, 95%CI: 1.25~2.75, P = 0.002); concomitant dementia (HR = 2.26, 95%CI: 1.43~3.59, P<0.001); stroke (HR = 2.09, 95% CI: 1.23-3.55, P = 0.007); heart disease (HR = 1.96, 95% CI: 1.41-2.73, P<0.001) and diabetes mellitus (HR = 2.39, 95% CI: 1.55-3.69, P<0.001). Sex, positive indirect immunofluorescence and hypertension were not associated with prognosis. CONCLUSION: Positive bullous pemphigoid 180 antibody, dementia, stroke, heart disease and diabetes mellitus were the prognostic factors for mortality in bullous pemphigoid.