Adjudin improves beta cell maturation, hepatic glucose uptake and glucose homeostasis.

AIMS/HYPOTHESIS: Recovering functional beta cell mass is a promising approach for future diabetes therapies. The aim of the present study is to investigate the effects of adjudin, a small molecule identified in a beta cell screen using zebrafish, on pancreatic beta cells and diabetes conditions in mice and human spheroids. METHODS: In zebrafish, insulin expression was examined by bioluminescence and quantitative real-time PCR (qPCR), glucose levels were examined by direct measurements and distribution using a fluorescent glucose analogue, and calcium activity in beta cells was analysed by in vivo live imaging. Pancreatic islets of wild-type postnatal day 0 (P0) and 3-month-old (adult) mice, as well as adult db/db mice (i.e. BKS(D)-Leprdb/JOrlRj), were cultured in vitro and analysed by qPCR, glucose stimulated insulin secretion and whole mount staining. RNA-seq was performed for islets of P0 and db/db mice. For in vivo assessment, db/db mice were treated with adjudin and subjected to analysis of metabolic variables and islet cells. Glucose consumption was examined in primary human hepatocyte spheroids. RESULTS: Adjudin treatment increased insulin expression and calcium response to glucose in beta cells and decreased glucose levels after beta cell ablation in zebrafish. Adjudin led to improved beta cell function, decreased beta cell proliferation and glucose responsive insulin secretion by decreasing basal insulin secretion in in vitro cultured newborn mouse islets. RNA-seq of P0 islets indicated that adjudin treatment resulted in increased glucose metabolism and mitochondrial function, as well as downstream signalling pathways involved in insulin secretion. In islets from db/db mice cultured in vitro, adjudin treatment strengthened beta cell identity and insulin secretion. RNA-seq of db/db islets indicated adjudin-upregulated genes associated with insulin secretion, membrane ion channel activity and exocytosis. Moreover, adjudin promoted glucose uptake in the liver of zebrafish in an insulin-independent manner, and similarly promoted glucose consumption in primary human hepatocyte spheroids with insulin resistance. In vivo studies using db/db mice revealed reduced nonfasting blood glucose, improved glucose tolerance and strengthened beta cell identity after adjudin treatment. CONCLUSIONS/INTERPRETATION: Adjudin promoted functional maturation of immature islets, improved function of dysfunctional islets, stimulated glucose uptake in liver and improved glucose homeostasis in db/db mice. Thus, the multifunctional drug adjudin, previously studied in various contexts and conditions, also shows promise in the management of diabetic states. DATA AVAILABILITY: Raw and processed RNA-seq data for this study have been deposited in the Gene Expression Omnibus under accession number GSE235398 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE235398 ).

Sleep deprivation reduced LPS-induced IgG2b production by up-regulating BMAL1 and CLOCK expression.

Sleep deprivation (SD) weakens the immune system and leads to increased susceptibility to infectious or inflammatory diseases. However, it is still unclear how SD affects humoral immunity. In the present study, sleep disturbance was conducted using an sleep deprivation instrument, and the bacterial endotoxin lipopolysaccharide (LPS) was used to activate the immune response. It was found that SD-pretreatment reduced LPS-induced IgG2b+ B cells and IgG2b isotype antibody production in lymphocytes of spleen. And, SD-pretreatment decreased the proportion of CD4+T cells, production of CD4+T cells derived TGF-ß1 and its contribution in helping IgG2b production. Additionally, BMAL1 and CLOCK were selectively up-regulated in lymphocytes after SD. Importantly, BMAL1 and CLOCK deficiency contributed to TGF-ß1 expression and production of IgG2b+ B cells. Thus, our results provide a novel insight to explain the involvement of BMAL1 and CLOCK under SD stress condition, and their roles in inhibiting TGF-ß1 expression and contributing to reduction of LPS induced IgG2b production.

Locoregional therapies combined with immune checkpoint inhibitors for liver metastases.

Immune checkpoint inhibitors (ICIs) have achieved remarkable success in clinical research and practice. Notably, liver metastasis is not sensitive to ICIs. Liver locoregional therapies can cause irreversible damage to tumor cells and release tumor antigens, thereby providing a rationale for immunotherapy treatments in liver metastasis. The combination therapy of ICIs with locoregional therapies is a promising option for patients with liver metastasis. Preclinical studies have demonstrated that combining ICIs with locoregional therapies produces a significantly synergistic anti-tumor effect. However, the current evidence for the efficacy of ICIs combined with locoregional therapies remains insufficient. Therefore, we review the literature on the mechanisms of locoregional therapies in treating liver metastasis and the clinical research progress of their combination with ICIs.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

Identifying novel acute pancreatitis sub-phenotypes using total serum calcium trajectories.

BACKGROUND: Acute pancreatitis (AP) has heterogeneous clinical features, and identifying clinically relevant sub-phenotypes is useful. We aimed to identify novel sub-phenotypes in hospitalized AP patients using longitudinal total serum calcium (TSC) trajectories. METHODS: AP patients had at least two TSC measurements during the first 24 h of hospitalization in the US-based critical care database (Medical Information Mart for Intensive Care-III (MIMIC-III) and MIMIC-IV were included. Group-based trajectory modeling was used to identify calcium trajectory phenotypes, and patient characteristics and treatment outcomes were compared between the phenotypes. RESULTS: A total of 4518 admissions were included in the analysis. Four TSC trajectory groups were identified: "Very low TSC, slow resolvers" (n = 65; 1.4% of the cohort); "Moderately low TSC" (n = 559; 12.4%); "Stable normal-calcium" (n = 3875; 85.8%); and "Fluctuating high TSC" (n = 19; 0.4%). The "Very low TSC, slow resolvers" had the lowest initial, maximum, minimum, and mean TSC, and highest SOFA score, creatinine and glucose level. In contrast, the "Stable normal-calcium" had the fewest ICU admission, antibiotic use, intubation and renal replace treatment. In adjusted analysis, significantly higher in-hospital mortality was noted among "Very low TSC, slow resolvers" (odds ratio [OR], 7.2; 95% CI, 3.7 to 14.0), "moderately low TSC" (OR, 5.0; 95% CI, 3.8 to 6.7), and "Fluctuating high TSC" (OR, 5.6; 95% CI, 1.5 to 20.6) compared with the "Stable normal-calcium" group. CONCLUSIONS: We identified four novel sub-phenotypes of patients with AP, with significant variability in clinical outcomes. Not only the absolute TSC levels but also their trajectories were significantly associated with in-hospital mortality.

Unveiling the Occurrence and Non-Negligible Role of Amino Sugars in Waste Activated Sludge Fermentation by an Enriched Chitin-Degradation Consortium.

Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (∼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of ∼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.

Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice.

Depressive disorders are a global mental health challenge that is closely linked to inflammation, especially in the post-COVID-19 era. The JAK-STAT pathway, which is primarily associated with inflammatory responses, is not fully characterized in the context of depressive disorders. Recently, a phase 3 retrospective cohort analysis heightened that the marketed JAK inhibitor tofacitinib is beyond immune diseases and has potential for preventing mood disorders. Inspired by these clinical facts, we investigated the role of the JAK-STAT signaling pathway in depression and comprehensively assessed the antidepressant effect of tofacitinib. We found that aberrant activation of the JAK-STAT pathway is highly conserved in the hippocampus of classical depressive mouse models: LPS-induced and chronic social defeat stress (CSDS)-induced depressive mice. Mechanistically, the JAK-STAT pathway mediates proinflammatory cytokine production and microgliosis, leading to synaptic defects in the hippocampus of both depressive models. Remarkably, the JAK inhibitor tofacitinib effectively reverses these phenomena, contributing to its antidepressant effect. These findings indicate that the JAK/STAT pathway could be implicated in depressive disorders, and suggest that the JAK inhibitor tofacitinib has a potential translational implication for preventing mood disorders far beyond its current indications.

Nonrestorative sleep and its associated factors in Chinese adolescents and the moderation effects of coffee or tea consumption.

BACKGROUND: Nonrestorative sleep (NRS) is related to numerous adverse outcomes. There is rare evidence of its associated factors, especially in Chinese adolescents. This study aimed to explore the factors associated with NRS in Chinese adolescents and the potential moderation effects of coffee or tea consumption. METHODS: This cross-sectional study invited adolescents attending Grades 7-11 in Nanjing, China, to complete a self-administered questionnaire, including their NRS, stress, anxiety, physical symptoms, depression, sociodemographics, and lifestyles. Linear regressions were applied to investigate the associated factors of their NRS, with the moderation effects of coffee or tea consumption and other characteristics being tested by additionally including their interactions. RESULTS: Totally 481 adolescents (49% male, age 15.5 ± 1.5 years) were enrolled, with the average global NRS score of 42.16 ± 7.57. Higher family income (ß = 2.01, P = 0.007), longer sleep duration (ß = 2.33, P = 0.011), and moderate after-class activity (ß = 1.50, P = 0.044) contributed less NRS, while higher educational level (ß = -2.60, P = 0.033), more coffee or tea consumption (ß = -1.68, P = 0.013), physical symptoms (ß = -3.85, P < 0.001), stress (ß = -0.23, P = 0.005), anxiety (ß = -1.54, P = 0.045), and depression (ß = -0.13, P = 0.014) contributed more NRS. Females (ß = 0.82, P = 0.005), older age (ß = -0.46, P = 0.029), and higher education level (ß = -1.68, P < 0.001) contributed less refreshment from sleep, more physical/medical symptoms of NRS, and less daytime function, respectively. Coffee or tea consumption moderated the associations of somatic symptoms (ß = 0.25, P = 0.021), stress (ß = 0.29, P = 0.022), anxiety (ß = 0.27, P = 0.005), and depression (ß = 0.17, P = 0.021) with NRS. CONCLUSIONS: Longer sleep duration, moderate after-class activity, reduced coffee or tea consumption, and promotion of physical and mental health may help reduce adolescents' NRS. Coffee or tea consumption may help buffer the negative associations of somatic symptoms, stress, anxiety, and depression with NRS.

The value of amide proton transfer imaging combined with serum CA125 levels in predicting lymph vascular invasion in cervical cancer before surgery.

BACKGROUND: Preoperative prediction of lymphovascular space invasion (LVSI) is crucial for improving the prognosis of patients with cervical cancer. PURPOSE: To evaluate the value of preoperative amide proton transfer (APT) imaging combined with serum CA125 levels for predicting LVSI in cervical cancer. MATERIAL AND METHODS: This retrospective study included 80 patients with cervical cancer who underwent preoperative magnetic resonance imaging, including APT imaging. Serum CA125 levels were measured using a fully automated immunoassay analyzer and chemiluminescence method. The presence of LVSI was determined based on the pathological results after surgery. RESULTS: Among the 40 patients who met the requirements, 29 had postoperative pathological confirmation of LVSI, while 11 did not. The areas under the receiver operating characteristic curves (AUC) of preoperative APT and CA125 levels predicting LVSI were 0.889 and 0.687, respectively. When the APT value was 2.9%, the corresponding Youden index was the highest (0.702), with a sensitivity of 79.3% and specificity of 90.9%. When the critical value of the preoperative serum CA15 level was 25.3 u/mL, the corresponding Youden index was the highest (0.508), with a sensitivity of 69.0% and a specificity of 81.8%. The sensitivity and specificity of preoperative APT imaging combined with serum CA125 in predicting LVSI were 82.7% and 100%, respectively, with a Youden's index of 0.828 and an AUC of 0.923. CONCLUSION: The combination of preoperative APT imaging and serum CA125 levels is valuable for predicting LVSI in cervical cancer. Diagnostic efficacy is highest when the APT value is >2.9% and the serum CA125 level is >25.3 u/mL.

Analysis of the efficacy of separation surgery for severe neurological compression in multiple myeloma: a retrospective analysis of 35 cases.

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

Which factors are associated with adverse prognosis in multiple myeloma patients after surgery? - preliminary establishment and validation of the nomogram.

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.

High levels of mitochondrial dynamics, autophagy, and apoptosis contribute to stable testicular status in hibernating Daurian ground squirrels.

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.

Van der Waals Engineering of Ultrafast Carrier Dynamics in Magnetic Heterostructures.

Heterostructures composed of the intrinsic magnetic topological insulator MnBi2Te4 and its nonmagnetic counterpart Bi2Te3 host distinct surface electronic band structures depending on the stacking order and exposed termination. Here, we probe the ultrafast dynamical response of MnBi2Te4 and MnBi4Te7 following near-infrared optical excitation using time- and angle-resolved photoemission spectroscopy and disentangle surface from bulk dynamics based on density functional theory slab calculations of the surface-projected electronic structure. We gain access to the out-of-equilibrium charge carrier populations of both MnBi2Te4 and Bi2Te3 surface terminations of MnBi4Te7, revealing an instantaneous occupation of states associated with the Bi2Te3 surface layer followed by carrier extraction into the adjacent MnBi2Te4 layers with a laser fluence-tunable delay of up to 350 fs. The ensuing thermal relaxation processes are driven by phonon scattering with significantly slower relaxation times in the magnetic MnBi2Te4 septuple layers. The observed competition between interlayer charge transfer and intralayer phonon scattering demonstrates a method to control ultrafast charge transfer processes in MnBi2Te4-based van der Waals compounds.

Toxicity of common biocides used in aquaculture to embryos and larvae of Brachymystax tsinlingensis Li.

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC50 ) values of the embryos and larvae were 1.71 and 0.22 mg l-1 for copper and 2.57 and 2.72 mg l-1 for zinc, respectively, whereas the MB LC50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l-1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l-1 for embryos and 0.03, 0.03 and 1.78 mg l-1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l-1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l-1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration.

Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Increased interbrain synchronization and neural efficiency of the frontal cortex to enhance human coordinative behavior: A combined hyper-tES and fNIRS study.

Coordination is crucial for individuals to achieve common goals; however, the causal relationship between coordination behavior and neural activity has not yet been explored. Interbrain synchronization (IBS) and neural efficiency in cortical areas associated with the mirror neuron system (MNS) are considered two potential brain mechanisms. In the present study, we attempted to clarify how the two mechanisms facilitate coordination using hypertranscranial electrical stimulation (hyper-tES). A total of 124 healthy young adults were randomly divided into three groups (the hyper-tACS, hyper-tDCS and sham groups) and underwent modulation of the right inferior frontal gyrus (IFG) during functional near-infrared spectroscopy (fNIRS). Increased IBS of the PFC or neural efficiency of the right IFG (related to the MNS) was accompanied by greater coordination behavior; IBS had longer-lasting effects on behavior. Our findings highlight the importance of IBS and neural efficiency of the frontal cortex for coordination and suggest potential interventions to improve coordination in different temporal windows.

Laser-reduced graphene oxide for a flexible liquid sliding sensing surface.

Flexible electronic skin is a flexible sensor system that imitates human skin. Recently, flexible sensors have been successfully developed. However, the droplet sliding sensing technology on a flexible electronic skin surface is still challenging. In this Letter, a flexible droplet sliding sensing surface is proposed and fabricated by laser-reduced graphene oxide (LRGO). The LRGO shows porous structures and low surface energy, which are beneficial for infusing lubricants and fabricating stable slippery surfaces. The slippery surface guarantees free sliding of droplets. The droplet sliding sensing mechanism is a combination of triboelectricity and electrostatic induction. After a NaCl droplet slides from lubricant-infused LRGO, a potential difference (∼0.2 mV) can be measured between two Ag electrodes. This study reveals considerable potential applications in intelligent robots and the medical field.

Metabolic syndrome score as an indicator in a predictive nomogram for lymph node metastasis in endometrial cancer.

BACKGROUND: Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. METHODS: This study is based on patients diagnosed with EC in Peking University People's Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. RESULTS: The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81-0.90) and 0.77 (95% CI: 0.77-0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82-0.93) and 0.80 (95% CI: 0.74-0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value. CONCLUSION: This model may promote risk stratification and individualized treatment, thus improving the prognosis.

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.

Two Dual-Function Zr/Hf-MOFs as High-Performance Proton Conductors and Amines Impedance Sensors.

In the field of sensing, finding high-performance amine molecular sensors has always been a challenging topic. Here, two highly stable 3D MOFs DUT-67(Hf) and DUT-67(Zr) with large specific surface areas and hierarchical pore structures were conveniently synthesized by solvothermal reaction of ZrCl4/HfCl4 with a simple organic ligand, 2,5-thiophene dicarboxylic acid (H2TDC) according to literature approach. By analyzing TGA data, it was found that the two MOFs have defects (unsaturated metal sites) that can interact with substrates (H2O and volatile amine gas), which is conducive to proton transfer and amine compound identification. Further experiments showed that at 100 °C and 98% relative humidity (RH), the optimized proton conductivities of DUT-67(Zr) and DUT-67(Hf) can reach the high values of 2.98 × 10-3 and 3.86 × 10-3 S cm-1, respectively. Moreover, the room temperature sensing characteristics of MOFs' to amine gases were evaluated at 68, 85 and 98% RHs, respectively. Impressively, the prepared MOFs-based sensors have the desired stability and higher sensitivity to amines. Under 68% RH, the detection limits of DUT-67(Zr) or DUT-67(Hf) for volatile amine gases were 0.5 (methylamine), 0.5 (dimethylamine) and 1 ppm (trimethylamine), and 0.5 (methylamine), 0.5 (dimethylamine) and 0.5 ppm (trimethylamine), respectively. As far as we know, this is the best performance of ammonia room temperature sensors in the past proton-conductive MOF sensors.