Characteristic cembrane-type diterpenoids with nitric oxide inhibitory activity from the gum resin of Boswellia carterii Birdw.

Five new characteristic cembrane-type diterpenoids (olibacartiols A-E, 1-5) were acquired from the gum resin of Boswellia carterii. The structures of these diterpenoids were characterized by detailed spectroscopic analysis, and compounds 1-3 were unambiguously confirmed by single-crystal X-ray diffraction experiments. The anti-inflammatory activities of the isolated compounds were evaluated using LPS-induced BV2 cell model and compounds 2-5 showed moderate NO inhibitory effects with IC50 values of 8.84 ±â€¯1.02, 9.82 ±â€¯1.95, 9.75 ±â€¯2.24, and 7.39 ±â€¯1.24 µM, respectively.

New alkaloids from Stemona tuberosa and structural revision of tuberostemonols P and R.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C17N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 µM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.

High adsorption of ammonia in a titanium-based metal-organic framework.

We report the high adsorption of NH3 in a titanium-based metal-organic framework, MFM-300(Ti), comprising extended [TiO6]∞ chains linked by biphenyl-3,3',5,5'-tetracarboxylate ligands. At 273 K and 1 bar, MFM-300(Ti) shows an exceptional NH3 uptake of 23.4 mmol g-1 with a record-high packing density of 0.84 g cm-3. Dynamic breakthrough experiments confirm the excellent uptake and separation of NH3 at low concentration (1000 ppm). The combination of in situ neutron powder diffraction and spectroscopic studies reveal strong, yet reversible binding interactions of NH3 to the framework oxygen sites.

Metal-ligand cross-link strategy engineered iron-doped dopamine-based superstructure as peroxidase-like nanozymes for detection of glucose.

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of being easy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308 mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000 µM, and the limit of detection is 17.5 µM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

Berberine increases the killing effect of pirarubicin on HCC cells by inhibiting ATG4B-autophagy pathway.

Pirarubicin (THP) is a new generation of cell cycle non-specific anthracycline-based anticancer drug. In the clinic, THP and THP combination therapies have been shown to be effective in hepatocellular carcinoma (HCC) patients with transcatheter arterial chemoembolisation (TACE) without serious side effects. However, drug resistance limits its therapeutic efficacy. Berberine (BBR), an isoquinoline alkaloid, has been shown to possess antitumour properties against various malignancies. However, the synergistic effect of BBR and THP in the treatment of HCC is unknown. In the present study, we demonstrated for the first time that BBR sensitized HCC cells to THP, including enhancing THP-induced growth inhibition and apoptosis of HCC cells. Moreover, we found that BBR sensitized THP by reducing the expression of autophagy-related 4B (ATG4B). Mechanistically, the inhibition of HIF1α-mediated ATG4B transcription by BBR ultimately led to attenuation of THP-induced cytoprotective autophagy, accompanied by enhanced growth inhibition and apoptosis in THP-treated HCC cells. Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.

Hsa_circ_0006260 Mediates Trophoblast Function by Fibronectin Type III Domains Containing Protein 5 via Interacting with miR-770-5p.

A series of studies have confirmed the relationship between circular RNAs (circRNAs) and metabolic diseases. Hsa_circ_0006260 has been reported to be lowly expressed in the placenta of gestational diabetes mellitus (GDM) patients, but the underlying mechanism and its biological functions remain obscure. Placental tissues were collected from 37 pregnant women with normal glucose tolerance (NGT) and 37 pregnant women with GDM. Expression changes of hsa_circ_0006260 in placentas and high glucose (HG)-stimulated HTR-8/SVneo cells were detected using real-time quantitative polymerase chain reaction. Cell viability and migration were determined by cell counting and transwell assays, respectively. Measurement of cytokines was done by enzyme-linked immunosorbent assay. Cell apoptosis was estimated by flow cytometry assay. The molecular mechanisms were identified using dual-luciferase reporter and RNA-binding protein immunoprecipitation assays. Hsa_circ_0006260 expression was remarkably lowered in GDM patient-derived placentas and HG-stimulated HTR-8/SVneo cells. Functionally, hsa_circ_0006260 overexpression weakened HG-mediated repression of HTR-8/SVneo cell viability and migration, as well as promotion of HTR-8/SVneo cell inflammatory response and apoptosis. Mechanistically, hsa_circ_0006260 functioned as a miR-770-5p decoy to mediate fibronectin type III domains containing protein 5 (FNDC5) expression. Ectopic expression of miR-770-5p weakened hsa_circ_0006260 overexpression-mediated repression of HG-induced HTR-8/SVneo cell dysfunction. Also, FNDC5 knockdown lessened miR-770-5p overexpression-mediated promotion of HG-induced HTR-8/SVneo cell dysfunction. Our findings manifested a novel mechanism by which hsa_circ_0006260 could lower HG-induced HTR-8/SVneo cell dysfunction by upregulating FNDC5 via binding to miR-770-5p, which shed new light on circRNA mediated GDM pathogenesis.

Generation of a human induced pluripotent stem cell line (SHUPLi002-A) from PBMCs of a healthy female donor.

Human induced pluripotent stem cells (iPSCs) have good multi-lineage differentiation potential, which is an ideal model for studying the pathogenesis of diseases and drug screening.Here, we generated an iPSC line, SHUPLi002-A, from peripheral blood mononuclear cells (PBMCs) of a healthy 28-year-old female individual using episomal vectors. SHUPLi002-A is characterized by expression of classical pluripotent stem cell markers as well as teratoma formation assays to evaluate their differentiation capacity in vivo.

Reconfigurable optoelectronic transistors for multimodal recognition.

Biological nervous system outperforms in both dynamic and static information perception due to their capability to integrate the sensing, memory and processing functions. Reconfigurable neuromorphic transistors, which can be used to emulate different types of biological analogues in a single device, are important for creating compact and efficient neuromorphic computing networks, but their design remains challenging due to the need for opposing physical mechanisms to achieve different functions. Here we report a neuromorphic electrolyte-gated transistor that can be reconfigured to perform physical reservoir and synaptic functions. The device exhibits dynamics with tunable time-scales under optical and electrical stimuli. The nonlinear volatile property is suitable for reservoir computing, which can be used for multimodal pre-processing. The nonvolatility and programmability of the device through ion insertion/extraction achieved via electrolyte gating, which are required to realize synaptic functions, are verified. The device's superior performance in mimicking human perception of dynamic and static multisensory information based on the reconfigurable neuromorphic functions is also demonstrated. The present study provides an exciting paradigm for the realization of multimodal reconfigurable devices and opens an avenue for mimicking biological multisensory fusion.

Effect of type 2 diabetes on cardiac arrhythmias in patients with obstructive hypertrophic cardiomyopathy.

AIMS: Type 2 diabetes (T2D), a prevalent cardiovascular disease, is linked with cardiac arrhythmias such as atrial fibrillation (AF) and ventricular arrhythmia. This study evaluated T2D's impact on these arrhythmias in patients with obstructive hypertrophic cardiomyopathy (OHCM). METHODS AND MATERIALS: We retrospectively analyzed the data of 75 patients with OHCM and T2D from two medical centers in China from 2011 to 2020. A propensity score-matched cohort of 150 patients without T2D was also analyzed. RESULTS: Altogether, 225 patients were included. The prevalence of supraventricular tachycardia (SVT), AF, and non-sustained ventricular tachycardia (NSVT) was higher in patients with HCM and T2D than in those without T2D. Multivariate logistic regression showed T2D as an independent risk factor for SVT (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.01-3.58, P = 0.04), AF (OR = 2.68, 95% CI = 1.27-5.67, P = 0.01), and NSVT (OR = 2.18, 95% CI = 1.04-4.57, P = 0.04). Further analysis identified fasting glucose and glycosylated hemoglobin levels as independent risk factors for AF and NSVT in patients with T2D. CONCLUSIONS: T2D independently increases the risk of cardiac arrhythmias (SVT, AF, NSVT) in OHCM patients. Furthermore, fasting glucose and glycosylated hemoglobin levels independently heighten AF and NSVT risk in OHCM patients with T2D.

A novel aldo-keto reductase gene, OsAKR1, from rice confers higher tolerance to cadmium stress in rice by an in vivo reactive aldehyde detoxification.

Elevated levels of cadmium (Cd) have the ability to impede plant development. Aldo-keto reductases (AKRs) have been demonstrated in a number of plant species to improve tolerance to a variety of abiotic stresses by scavenging cytotoxic aldehydes; however, only a few AKRs have been identified to improve Cd tolerance. The OsAKR1 gene was extracted and identified from rice here. After being exposed to Cd, the expression of OsAKR1 dramatically rose in both roots and shoots, although more pronounced in roots. According to a subcellular localization experiment, the nucleus and cytoplasm are where OsAKR1 is primarily found. Mutants lacking OsAKR1 exhibited Cd sensitive phenotype than that of the wild-type (WT) Nipponbare (Nip), and osakr1 mutants exhibited reduced capacity to scavenge methylglyoxal (MG). Furthermore, osakr1 mutants exhibited considerably greater hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, and increased catalase (CAT) activity in comparison to Nip. The expression of three isomeric forms of CAT was found to be considerably elevated in osakr1 mutants during Cd stress, as demonstrated by quantitative real-time PCR analysis, when compared to Nip. These results imply that OsAKR1 controlled rice's ability to withstand Cd by scavenging harmful aldehydes and turning on the reactive oxygen species (ROS) scavenging mechanism.

Oxyberberine sensitizes liver cancer cells to sorafenib via inhibiting NOTCH1-USP7-c-Myc pathway.

BACKGROUND: Sorafenib is the first-line therapy for patients with advanced-stage HCC, but its clinical cure rate is unsatisfactory due to adverse reactions and drug resistance. Novel alternative strategies to overcome sorafenib resistance are urgently needed. Oxyberberine (OBB), a major metabolite of berberine in vivo, exhibits potential antitumor potency in various human malignancies, including liver cancer. However, it remains unknown whether and how OBB sensitizes liver cancer cells to sorafenib. METHODS: Cell viability, trypan blue staining and flow cytometry assays were employed to determine the synergistic effect of OBB and sorafenib on killing HCC cells. PCR, western blot, co-immunoprecipitation and RNA interference assays were used to decipher the mechanism by which OBB sensitizes sorafenib. HCC xenograft models and clinical HCC samples were utilized to consolidate our findings. RESULTS: We found for the first time that OBB sensitized liver cancer cells to sorafenib, enhancing its inhibitory effect on cell growth and induction of apoptosis in vitro. Interestingly, we observed that OBB enhanced the sensitivity of HCC cells to sorafenib by reducing ubiquitin-specific peptidase 7 (USP7) expression, a well-known tumor-promoting gene. Mechanistically, OBB inhibited notch homolog 1-mediated USP7 transcription, leading to the downregulation of V-Myc avian myelocytomatosis viral oncogene homolog (c-Myc), which synergized with sorafenib to suppress liver cancer. Furthermore, animal results showed that cotreatment with OBB and sorafenib significantly inhibited the tumor growth of liver cancer xenografts in mice. CONCLUSIONS: These results indicate that OBB enhances the sensitivity of liver cancer cells to sorafenib through inhibiting notch homolog 1-USP7-c-Myc signaling pathway, which potentially provides a novel therapeutic strategy for liver cancer to improve the effectiveness of sorafenib.

Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

BACKGROUND: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear. METHODS: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node. RESULTS: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke. CONCLUSIONS: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.

Virtual reality-based dementia educational programmes for formal and informal caregivers of people with dementia: A scoping review.

AIM: To map evidence of the existing virtual reality-based dementia educational programmes and the effects of these educational programmes on dementia formal and informal caregivers. DESIGN: A scoping review. METHODS: A comprehensive search of nine databases was conducted to find studies from the inception of the databases to October 2023. Two authors independently screened the titles and abstracts related to the eligibility criteria. Full texts of potentially relevant studies were read by one author and checked by a second. Data extraction and synthesis using NVivo 12 were undertaken by one author and checked by two other authors. RESULTS: Nineteen studies published between 2002 and 2022. The four randomised controlled studies and five qualitative studies were of moderate to good methodological quality. The 10 quasi-experimental studies were of weak to moderate quality. Fifteen virtual reality-based educational programmes had a positive influence on formal and informal caregivers, including improving caregivers' perceptions changing attitudes towards people with dementia, while the nursing competence of formal caregivers did not improve in short term. Educational programmes that covered dementia-related information and care strategies better improved the knowledge level of dementia formal and informal caregivers. CONCLUSIONS: The qualitative and quantitative studies of moderate to good quality included in this study support the idea that virtual reality-based dementia educational programmes may be a safe and effective way and have potential benefits for improving knowledge, perceptions, attitudes and nursing competence. IMPACT: This scoping review will provide an emerging teaching model for formal and informal caregivers of people with dementia and help them better understand the types and the influence of virtual reality-based dementia educational programmes. REPORTING METHOD: PRISMA-ScR. NO PATIENT OR PUBLIC CONTRIBUTION: Not required as this review in accordance with the aim to map existing literature from the dementia formal and informal caregivers' perspective.

Life experience and identity of spousal caregivers of people with dementia: A qualitative systematic review.

BACKGROUND: The number of people with dementia is on the rise worldwide, and dementia care has become the focus of global health services. People with dementia are primarily cared for by informal caregivers, with spouses seen as a particularly vulnerable group. Focusing on the spousal caregiving experience and having a good caregiver identity contributes to group bonding and enhanced social support. OBJECTIVE: To explore the dynamic changes that occur in the caregiving experience of spouse caregivers and explicate the identity of spouses during this process alongside its causes. DESIGN: A qualitative systematic review. DATA SOURCE: The following eight electronic databases were searched: PubMed, Web of Science (Core Collection), The Cochrane Library, Embase, CINAHL and CNKI, WanFang and Vip. REVIEW METHODS: The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) and Joanna Briggs Institute Reviewer's Manual criteria were used to report the results. Study screening and data extraction were conducted independently by two reviewers, and quality was assessed using the Joanna Briggs Institute's Qualitative Research Standard Assessment tool. Data synthesis was performed using thematic analysis. RESULTS: A total of 15 studies were included and synthesized into three analytical themes: (1) attitudes and emotions toward dementia, (2) emotional ups and downs in dementia care, and (3) who am "I". In binary care, patience and marital responsibilities are identified as facilitators, while care burden and social isolation are identified as hindrances. In addition, gender differences were identified as influencers of identity. CONCLUSIONS: In this review, spouse identity of people with dementia is complex and affects caregiving experience together with dementia cognition. Disease cognition, caregiving burden and social isolation are identified. Interventions for barriers are suggested to enhance social support.

Effects of common lifestyle factors on obstructive sleep apnea: precautions in daily life based on causal inferences.

Background: This study aimed to evaluate the causal impact of common modifiable lifestyles on obstructive sleep apnea (OSA), which is beneficial for recommendations to prevent and manage OSA. Method: Published genome-wide association study (GWAS) summary statistics were used to perform two-sample Mendelian randomization (MR). Variants associated with each exposure of smoking, drinking, and leisure sedentary behaviors at the genetic level were used as instrumental variables (IVs). Then, inverse-variance weighting (IVW) was considered the primary result for causality. Moreover, several complimented approaches were also included to verify the observed associations. MR-PRESSO and MR-Egger intercept were applied to test the horizontal pleiotropy. To assess heterogeneity, Cochran's Q test by IVW and MR-Egger were applied. Results: Regular smoking history increased OSA risk in all applied approaches [OR (95% CI)IVW = 1.28 (1.12, 1.45), p = 1.853 × 10-4], while the causality of lifetime smoking index [OR (95% CI)IVW = 1.39 (1.00, 1.91), p = 0.048], alcohol intake frequency [outliers removed OR (95% CI)IVW = 1.26 (1.08, 1.45), p = 0.002], and coffee intake behavior [OR (95% CI)IVW = 1.66 (1.03, 2.68), p = 0.039] on OSA risk were not always consistent in other approaches. In addition, no robust causal associations were observed for the effect of sedentary leisure behaviors on OSA risk. In sensitivity analysis, we observed no sign of horizontal pleiotropy or heterogeneity. Conclusion: Ever regularly smoking has a robust causal role in increasing OSA risk, which should be discouraged as precautions from developing OSA.

Flexible cellulose nanofibers/MXene composite films for UV-shielding packaging.

Cellulose nanofibers (CNF) based films are promising packaging materials, but the lack of special functions (especially UV-shielding property) usually restrict their further applications. In this work, MXene was incorporated into the CNF film by a direct solvent volatilization induced film forming method to study its UV-shielding property for the first time, which avoided the using of a vacuum filtration equipment. The composite films containing glycerin could be folded repeatedly without breaking, showing good flexibility. The structure and properties of MXene/CNF composite films (CMF) were characterized systematically. The results showed that MXene distributed uniformly in the CNF film matrix and there was strong hydrogen bonding interaction between CNF and MXene. The tensile strength and Young's modulus of the composite films could reach 117.5 MPa and 2.23 GPa, which was 54.1 % and 59.2 % higher than those of pure CNF film, respectively. With the increase of MXene content, both the UVA and UVB shielding percentages increased significantly from 17.2 % and 25.5 % to 100.0 %, showing excellent UV-shielding property. Moreover, CMF exhibited a low oxygen permeability (OP) value of 0.39 cc µm d-1 m-2 kPa-1, a low water vapor permeability (WVP) value of 5.13 × 10-11 g-1s-1Pa-1 and a high antibacterial rate against E. coli (94.1 % at 24 h), showing potential application in the packaging field.

Adequate iodine nutrition and higher salt intake in Chinese adults aged 18-59 years recommended by international organizations.

Iodine deficiency and excessive salt intake have adverse health effects. This study evaluated the iodine level and salt intake in Chinese adults aged 18-59 years after implementing the salt reduction program and compared with both the World Health Organization (WHO) and Chinese recommendations. Adults aged 18-59 years were randomly selected using multi-stage stratified random sampling in coastal urban area (CUA), non-coastal urban area (Non-CUA), coastal rural area (CRA), and non-coastal rural area (Non-CRA) of Fujian Province, China. Iodine, sodium, and creatinine concentrations in spot urine samples were measured. Knudsen equation was used to determine 24-h urinary iodine and sodium excretion. The median urinary iodine concentration (mUIC) and urinary sodium concentration (mUNaC) among adults (n = 3513) were 132.0 µg/L and 4.0 g/d, respectively. The mUIC and median daily iodine intake in CUA, Non-CUA, CRA and Non-CRA were 112.1, 127.5, 128.5, 167.5 µg/L and 189.6, 182.5, 199.4, 236.0 µg/d, respectively. The mUNaC and median daily salt intake (mDSI) in these four areas were 2.4, 2.8, 2.9, 2.9 g/L and 9.8, 10.4, 10.4, 10.6 g/d, respectively. The mUIC and DII of residents were higher in the Non-CRA than in the other three areas (P < 0.05). The UNaC and DSI of residents were lower in the CUA than in the other three areas (P < 0.05). The logistic regression demonstrated that the people living in CUA and Non-CUA consumed less salt compared with those in Non-CRA. Except for Non-CUA, the DII was lower (< 150 µg/d) among women of childbearing age in the low-salt intake group (< 5 g/d) compared with the high-salt intake group (≥ 5 g/d) (P < 0.05). Iodine nutrition in Chinese adults aged 18-59 years was sufficient, but the salt intake was substantially higher than the WHO and Chinese recommendations. Further policy implementation is needed to reduce salt intake and improve the monitoring of iodine levels in Chinese adults, especially in women of childbearing age.

The benefits of hypoglycemic therapy for patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is often associated with glycemic abnormalities. This study is conducted to investigate the effects of hypoglycemic therapy on OSA-related indicators. METHOD: We systematically searched Web of Science, PubMed, Embase, and the Cochrane Library for articles on OSA patients receiving any hypoglycemic drugs, published until December 25, 2022. Seven original studies were finally included. The proposal was registered with PROSPERO (CRD42022351206). RESULTS: In summary, in addition to reduced glycosylated hemoglobin A1c (HbA1c), we found that hypoglycemic treatment can lower the apnea-hypopnea index (AHI) by 7.07/h (p = 0.0001). Although long-term treatment (> 12 weeks) achieved a more significant reduction in HbA1c (- 1.57% vs. - 0.30%) compared to short-term treatment (≤ 12 weeks), there was no significant difference between the two in terms of AHI (intergroup p-value = 0.27). We also found that patients using sodium glucose cotransporter 2 inhibitors (SGLT2i) experienced a greater reduction in AHI (- 11.00/h, p < 0.00001). Additionally, hypoglycemic treatment also showed certain improvements in related indicators like Epworth Sleepiness Scale, body mass index, and blood pressure. CONCLUSIONS: Our results affirm the benefits of hypoglycemic treatment for OSA patients and highlight the notable effect of SGLT2i. Further researches are needed to help doctors gain a comprehensive understanding of the interaction between OSA and glycemic abnormalities.

Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Mechanism interpretation of Guhan Yangshengjing for protection against Alzheimer's disease by network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangshengjing (GHYSJ) is an effective prescription for delaying progression of Alzheimer's disease (AD) based on the ancient Chinese medical classics excavated from Mawangdui Han Tomb. Comprising a combination of eleven traditional Chinese herbs, the precise protective mechanism through which GHYSJ acts on AD progression remains unclear and has significant implications for the development of new drugs to treat AD. AIM OF THE STUDY: To investigate the mechanism of GHYSJ in the treatment of AD through network pharmacology and validate the results through in vitro experiments. MATERIALS AND METHODS: Chemical composition-target-pathway network and protein-protein interaction network were constructed by network pharmacology to predict the potential targets of GHYSJ for the treatment of AD. The interaction relationship between active ingredients and targets was verified by molecular docking and molecular force. Furthermore, the chemical constituents of GHYSJ were analyzed by LC-MS and HPLC, the effects of GHYSJ on animal tissues were analyzed by H&E staining. An Aß-induced SH-SY5Y cellular model was established to validate the core pathways and targets predicted by network pharmacology and molecular docking. RESULTS: The results of the network pharmacology analysis revealed a total of 155 bioactive compounds capable of crossing the blood-brain barrier and interacting with 677 targets, among which 293 targets specifically associated with AD, which mainly participated in and regulated the amyloid aggregation pathway and PI3K/Akt signaling pathway, thereby treating AD. In addition, molecular docking analysis revealed a robust binding affinity between the principal bioactive constituents of GHYSJ and crucial targets implicated in AD. Our findings were further substantiated by in vitro experiments, which demonstrated that Liquiritigenin and Ginsenosides Rh4, crucial constituents of GHYSJ, as well as GHYSJ pharmaceutic serum, exhibited a significant down-regulation of BACE1 expression in Aß-induced damaged SH-SY5Y cells. This study provides valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD and secondary development of GHYSJ prescription. CONCLUSION: Through network pharmacology, molecular docking, LC-MS, and cellular experiments, GHYSJ was initially confirmed to delay the progression of AD by regulating the expression of BACE1 in Amyloid aggregation pathway. Our observations provided valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD.