External-beam radiotherapy after transarterial chemoembolization (TACE) versus TACE alone for treatment of inoperable HCC: A randomized phase III trial.

PURPOSE: To compare the outcomes of transarterial chemoembolization (TACE) alone with those of TACE combined with external-beam radiotherapy (EBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized study. METHODS AND MATERIALS: From 2017 to 2022, 74 HCC patients with tumors confined to the liver without vascular invasion were treated with either TACE only (TACE group, 39 patients) or TACE combined with EBRT (TACE+EBRT group, 35 patients). The primary outcome measured was overall survival (OS). Secondary outcomes included progression-free survival (PFS), local tumor control (LC), and the assessment of treatment-related toxicity. RESULTS: Due to slow accrual, the trial was closed prematurely after enrolling 74 patients. All patients received two cycles of TACE before randomization. The TACE and TACE+EBRT groups showed comparable patient and tumor characteristics. The TACE group underwent an median of 3 TACE cycles, and the TACE+EBRT group received two cycles of TACE and a median of 5,500 cGy in 15 fractions. For the TACE group, the median LC duration was 13.1 months, while for the TACE+EBRT group, the median LC was not achieved (P<0.001). The PFS was recorded at 11.6 months in the TACE group compared to 15.4 months in the TACE+EBRT group (P=0.072). The median OS reached 36.8 months for the TACE group and extended to 47.1 months for the TACE+EBRT group (P=0.654). The incidence of toxicity was comparable between both groups. CONCLUSIONS: Although the number of patients enrolled in this clinical trial did not meet expectations. TACE combined with EBRT was shown to be more effective than TACE alone in improving local control (LC) without increasing toxicity, while PFS and OS was slightly improved. TACE+EBRT can be used as a standard treatment option for patients with inoperable but confined intrahepatic HCC.

Mobile Phone Addiction and Psychological Capital Mediates the Relationship Between Life Satisfaction and Learning Burnout in Chinese Medical Postgraduate Students: A Structural Equation Model Analysis.

Purpose: To analyze the relationship between life satisfaction and learning burnout, and explore the mediating effect of mobile phone addiction and psychological capital, and to provide a theoretical basis for the study of measures for medical postgraduate students to maintain a positive psychological state and keep interest and enthusiasm in academic life. Methods: Convenience cluster sampling was used to recruit 628 medical postgraduate students in Chongqing, China. The Learning Burnout Questionnaire (LBQ), life satisfaction self-rated item, Mobile Phone Addiction Tendency Scale (MPATS), and the Psychological Capital Questionnaire (PCQ) were used to examine participants. Hierarchical regression was used to analyze the effect of life satisfaction, mobile phone addiction, and psychological capital on learning burnout. A structural equation model (SEM) with maximum likelihood was used to evaluate the mediating effect of mobile phone addiction and psychological capital on the relationship between life satisfaction and learning burnout. The bootstrap method was used to confirm the significance of the mediating effect. Results: The average learning burnout score was (55.81±10.55). Results of hierarchical regression revealed that life satisfaction and psychological capital had a significant negative predictive effect on learning burnout, and mobile phone addiction had a positive predictive effect on learning burnout (p<0.05). The SEM revealed that the total and direct effects of life satisfaction on learning burnout were significant, and the mediating effects of mobile phone addiction and psychological capital between life satisfaction and learning burnout were significant (p<0.05). Conclusion: Life satisfaction is a direct predictor of learning burnout among Chinese medical postgraduate students, and this relationship is mediated by mobile phone addiction and psychological capital.

Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies.

BACKGROUND: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM: To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS: Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS: A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION: In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.

Quantitative separation of CEST effect by Rex-line-fit analysis of Z-spectra.

The process of chemical exchange saturation transfer (CEST) is quantified by evaluating a Z-spectra, where CEST signal quantification and Z-spectra fitting have been widely used to distinguish the contributions from multiple origins. Based on the exchange-dependent relaxation rate in the rotating frame (Rex), this paper introduces an additional pathway to quantitative separation of CEST effect. The proposed Rex-line-fit method is solved by a multi-pool model and presents the advantage of only being dependent of the specific parameters (solute concentration, solute-water exchange rate, solute transverse relaxation, and irradiation power). Herein we show that both solute-water exchange rate and solute concentration monotonously vary with Rex for Amide, Guanidino, NOE and MT, which has the potential to assist in solving quantitative separation of CEST effect. Furthermore, we achieve Rex imaging of Amide, Guanidino, NOE and MT, which may provide direct insight into the dependency of measurable CEST effects on underlying parameters such as the exchange rate and solute concentration, as well as the solute transverse relaxation.

A common variant in PIK3CG gene associated with the prognosis of heart failure.

Phosphoinositide 3-kinase γ (PI3Kγ) is G-protein-coupled receptor-activated lipid kinase with both kinase-dependent and kinase-independent activity. Plenty of evidence have demonstrated that PI3Kγ participated in TAC and I/R-induced myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in the PI3Kγ gene (PIK3CG) were associated with the prognosis of HF in the Chinese Han population. Through re-sequencing and genotyping, we finally identified a common variant in the 3'UTR of PIK3CG strongly associated with the prognosis of HF in two-stage population: adjusted p = 0.007, hazard ratio = 0.56 (0.36-0.85) in the first cohort and adjusted p = 0.024, hazard ratio = 0.39 (0.17-0.88) in the replicated cohort. A series of functional assays revealed that rs10215499-A allele suppressed PIK3CG translation by facilitating has-miR-133a-3p binding, but not the G allele. Subjects carrying the GG genotype showed higher mRNA and protein level than those with AA and AG genotype. Furthermore, overexpression of PIK3CG could protect AC16 from hypoxia/reoxygenation (H/R)-induced apoptosis, while the case was opposite for PIK3CG silencing. In conclusion, common variant rs10215499 in the 3'-UTR of PIK3CG might affect the prognosis of HF by interfering with miR-133a-3p binding and PIK3CG is a promising target for HF treatment in the future.

Sequence-Dependent Single-Molecule DNA Sensing Using Covalent Organic Framework Nanopores.

Enzyme-free single-molecule sequencing has the potential to significantly expand the application of nanopore technology to DNA, proteins, and saccharides. Despite their advantages over biological nanopores and natural suitability for enzyme-free single-molecule sequencing, conventional solid-state nanopores have not yet achieved single-molecule DNA sequencing. The biggest challenge for the accuracy of single-molecule sequencing using solid-state nanopores lies in the precise control of the pore size and conformity. In this study, we fabricated nanopore devices by covering the tip of a quartz nanopipette with ultrathin two-dimensional (2D) covalent organic framework (COF) nanosheets (pore size ≈ 1.1 nm). The size of the periodically arranged nanopores in COF is comparable to that of protein nanopores, and the structure of each COF nanopore is consistent at the atomic scale. The COF nanopore device could roughly distinguish dAMP, dCMP, dGMP, and dTMP. Furthermore, a certain percentage of the current blockades originating from 150 nucleotides model DNA molecules (13.5% for dA50dC50dA50 and 11.1% for dC50dA50dC50) show distinct DNA sequence-specific concave and convex resistive current patterns. The finite element simulation confirmed that the current blockade pattern of a DNA molecule passing through a COF nanopore is dependent on the relative location of the nanopore with respect to the wall of the nanopipette. Our study is a significant step toward single-molecule DNA sequencing by solid-state nanopores.

Causal relationship between immune cells and risk of myocardial infarction: evidence from a Mendelian randomization study.

Background: Atherosclerotic plaque rupture is a major cause of heart attack. Previous studies have shown that immune cells are involved in the development of atherosclerosis, but different immune cells play different roles. The aim of this study was to investigate the causal relationship between immunological traits and myocardial infarction (MI). Methods: To assess the causal association of immunological profiles with myocardial infarction based on publicly available genome-wide studies, we used a two-sample mendelian randomization (MR) approach with inverse variance weighted (IVW) as the main analytical method. Sensitivity analyses were used to assess heterogeneity and horizontal pleiotropy. Results: A two-sample MR analysis was conducted using IVW as the primary method. At a significance level of 0.001, we identified 47 immunophenotypes that have a significant causal relationship with MI. Seven of these were present in B cells, five in cDC, four in T cells at the maturation stage, six in monocytes, five in myeloid cells, 12 in TBNK cells, and eight in Treg cells. Sensitivity analyses were performed to confirm the robustness of the MR results. Conclusions: Our results provide strong evidence that multiple immune cells have a causal effect on the risk of myocardial infarction. This discovery provides a new avenue for the development of therapeutic treatments for myocardial infarction and a new target for drug development.

Use of the Omaha System nursing model on nutritional status outcomes in peritoneal dialysis patients.

OBJECTIVE: To construct and apply a risk screening and intervention system for malnutrition in peritoneal dialysis patients based on the Omaha System. MATERIALS AND METHODS: A total of 75 peritoneal dialysis patients were randomly divided into control (38 cases) and intervention group (37 cases). The control group received routine operation training and health education, and the intervention group implemented a nutritional management plan based on the Omaha System. The modified quantitative subjective comprehensive nutritional scale (MQSGA) score, kidney disease dietary compliance attitude (RAAQ) and behavior (RABQ) score, body mass index (BMI), serum albumin (ALB), prealbumin (PA), and hemoglobin (Hb) were observed. RESULTS: Before intervention, there was no significant difference in these indicators between the two groups (p > 0.05). After 6 months, the MQSGA score in the intervention group was significantly lower than that in the control group (p < 0.05). RAAQ score and RABQ score in the intervention group were higher than those in the control group and (p < 0.05), and the nutritional indicators in the intervention group, such as BMI, ALB, PA, and Hb, were higher than those in the control group (p < 0.05). CONCLUSION: A nutritional management plan based on the Omaha System can help improve the nutrition condition of peritoneal dialysis patients, and improve the dietary compliance of chronic kidney disease patients.

High-Performance AgSbTe2 Thermoelectrics: Advances, Challenges, and Perspectives.

Environmental-friendless and high-performance thermoelectrics play a significant role in exploring sustainable clean energy. Among them, AgSbTe2 thermoelectrics, benefiting from the disorder in the cation sublattice and interface scattering from secondary phases of Ag2Te and Sb2Te3, exhibit low thermal conductivity and a maximum figure-of-merit ZT of 2.6 at 573 K via optimizing electrical properties and addressing phase transition issues. Therefore, AgSbTe2 shows considerable potential as a promising medium-temperature thermoelectric material. Additionally, with the increasing demands for device integration and portability in the information age, the research on flexible and wearable AgSbTe2 thermoelectrics aligns with contemporary development needs, leading to a growing number of research findings. This work provides a detailed and timely review of AgSbTe2-based thermoelectrics from materials to devices. Principles and performance optimization strategies are highlighted for the thermoelectric performance enhancement in AgSbTe2. The current challenges and future research directions of AgSbTe2-based thermoelectrics are pointed out. This review will guide the development of high-performance AgSbTe2-based thermoelectrics for practical applications.

Advancing flexible thermoelectrics for integrated electronics.

With the increasing demand for energy and the climate challenges caused by the consumption of traditional fuels, there is an urgent need to accelerate the adoption of green and sustainable energy conversion and storage technologies. The integration of flexible thermoelectrics with other various energy conversion technologies plays a crucial role, enabling the conversion of multiple forms of energy such as temperature differentials, solar energy, mechanical force, and humidity into electricity. The development of these technologies lays the foundation for sustainable power solutions and promotes research progress in energy conversion. Given the complexity and rapid development of this field, this review provides a detailed overview of the progress of multifunctional integrated energy conversion and storage technologies based on thermoelectric conversion. The focus is on improving material performance, optimizing the design of integrated device structures, and achieving device flexibility to expand their application scenarios, particularly the integration and multi-functionalization of wearable energy conversion technologies. Additionally, we discuss the current development bottlenecks and future directions to facilitate the continuous advancement of this field.

Preparation of low-cost sludge-based highly porous biochar for efficient removal of refractory pollutants from agrochemical and pharmaceutical wastewater.

Producing a high-performance sludge biochar through a feasible method is a great challenge and is crucial for practicability. Herein, we reported a highly porous sludge biochar synthesized from agrochemical-pharmaceutical and municipal sludge blends through a novel pyrolysis-acid treatment-post pyrolysis method. The optimized biochar named ASMS91 obtained interconnected pores with a total pore volume of 0.894 cm3/g and a surface area of 691.4 m2/g through extended acid wash and subsequent post-pyrolysis, which is superior to non-activated sludge biochar. ASMS91 removed 45.3 % of wastewater COD (156 mg/L) in 24 h, which was rapid and higher performance than commercial activated carbon (1000 iodine number). This outstanding performance is due to its high adsorption ability of long-chain aliphatic compounds (e.g., 2,4-Di-tert-butylphenol, neophytadiene and eicosane) into mesopores, which accounts for 71.8 % of pore filling. ASMS91 was highly recyclable, and adsorption was reduced by only 5.3 % after the 4th cycle. It also outperformed other sludge biochar in literature in removing perfluorooctanoic acid (PFOA), 6:2 fluorotelomer sulfonate (6:2 FTS), sulfamethoxazole, methylene blue, and methylene orange. Finally, the feasibility of our proposed method was validated by a brief techno-economic analysis. This feasible approach may support future research regarding sludge valorization and low-cost chemical wastewater treatment.

Impact of different concentration iodinated contrast media on pain and comfort in abdominal computed tomography.

OBJECTIVES: To investigate whether high concentration iodinated contrast media (CM), compared with low concentration CM, could reduce pain and discomfort levels in patients who had level II and III venous conditions. METHODS: This prospective, single-center study enrolled patients who had level II and III venous conditions and underwent abdominal contrast-enhanced CT scan between July 2021 and February 2022. The venous condition to establish peripheral venous access for CM injection was graded using the Intravenous Access Scoring system, of which level II and III indicated poor venous condition and difficult venous access. Patients received iomeprol 400 in high concentration group and ioversol 320 in low group at an identical iodine delivery rate of 1.12 gI/s. The primary outcomes were pain and comfort levels. The secondary outcomes included adverse events and image quality. Patients rated pain intensity via Numerical Rating Scale and comfort level via Visual Analogue Scale with higher scores indicating higher levels of pain and discomfort. Quantitative and qualitative image assessment were compared between two groups. Continuous variables were compared using Student's t test or Mann-Whitney U test. Categorical variables were compared using χ2 test, χ2 test for trend or Fisher's exact test. RESULTS: A total of 206 patients (mean age, 60.13 ± 12.14 years; 81 males) were included with 99 in the high concentration group and 107 in the low concentration group. The high group had significantly lower pain scores (median 1 [IQR: 0-2] vs 2 (IQR 2-4), p < 0.001) and comfort scores (1 [IQR: 0-3] vs 3 [IQR: 2-5], p < 0.001) than the low group. Incidence of CM extravasation did not significantly differ (1.0 % vs 4.5 %, p = 0.214). No hypersensitivity reaction was observed. Qualitative assessment showed higher clarity scores of intrahepatic hepatic artery and portal vein in the high group. Quantitative assessment results were comparable between two groups. CONCLUSION: High concentration iodinated CM could lower pain intensity and improve comfort levels without comprising image quality of CT scan. High concentration CM is a preferable choice in patients with poor venous conditions during contrast-enhanced CT scan.

New CRISPR/Cas9-based Fgfr2C361Y/+ mouse model of Crouzon syndrome exhibits skull and behavioral abnormalities.

Crouzon syndrome (CS), a syndromic craniosynostosis, is a craniofacial developmental deformity caused by mutations in fibroblast growth factor receptor 2 (FGFR2). Previous CS mouse models constructed using traditional gene editing techniques faced issues such as low targeting efficiency, extended lineage cycles, and inconsistent and unstable phenotypes. In this study, a CRISPR/Cas9-mediated strategy was employed to induce a functional augmentation of the Fgfr2 point mutation in mice. Various techniques, including bone staining, micro-CT, histological methods, and behavioral experiments, were employed to systematically examine and corroborate phenotypic disparities between mutant mice (Fgfr2C361Y/+) and their wild-type littermates. Confirmed via PCR-Sanger sequencing, we successfully induced the p.Cys361Tyr missense mutation in the Fgfr2 IIIc isoform of the extracellular domain (corresponding to the p.Cys342Tyr mutation in humans) based on Fgfr2-215 transcript (ENSMUST00000122054.8). Fgfr2C361Y/+ mice exhibited characteristics consistent with the phenotypic features associated with CS, including skull-vault craniosynostosis, skull deformity, shallow orbits accompanied by exophthalmos, midface hypoplasia with malocclusion, and shortened skull base, notably without any apparent limb defects. Furthermore, mutant mice displayed behavioral abnormalities encompassing deficits in learning and memory, social interaction, and motor dysfunction, without anxiety-related disorders. Histopathological examination of the hippocampal region revealed structural abnormalities, suggesting possible brain development impairment secondary to craniosynostosis. In conclusion, we constructed a novel gene-edited Fgfr2C361Y/+ mice strain based on CRISPR/Cas9, which displayed skull and behavioral abnormalities, serving as a new model for studying genetic molecular mechanisms and exploring treatments for CS. KEY MESSAGES: CRISPR/Cas9 crafted a Crouzon model by enhancing Fgfr2-C361Y in mice. Fgfr2C361Y/+ mice replicate CS phenotypes-craniosynostosis and midface anomalies. Mutant mice show diverse behavioral abnormalities, impacting learning and memory. Fgfr2C361Y/+ mice offer a novel model for cranial suture studies and therapeutic exploration.

Classification of anatomy and treatment approaches for aneurysms originating from the proximal of the A1 segment of the anterior cerebral artery in clinical settings.

Objective: To explore the spatial relationship between A1 segment proximal anterior cerebral artery aneurysms and their main trunks, classify them anatomically and develop targeted treatment strategies. Methods: This single-center retrospective analysis involved 39 patients diagnosed with aneurysms originating from the proximal of A1 segment of the anterior cerebral artery (2014-2023). Classify the patient's aneurysm into 5 types based on the location of the neck involving the carrier artery and the spatial relationship and projection direction of the aneurysm body with the carrier artery, and outcomes from treatment methods were compared. Results: Among 39 aneurysms, 18 cases underwent endovascular intervention treatment, including 6 cases of stent assisted embolization, 1 case of flow-diverter embolization, 5 cases of balloon assisted embolization, and 6 cases of simple coiling. At discharged, the mRS score of all endovascularly treated patients was 0, and the GOS score was 5 at 6 months after discharge. At discharge, the mRS score of microsurgical clipping treated patients was 0 for 15 cases, 3 for 1 case, 4 for 1 case and 5 for 2 cases. Six months after discharge, the GOS score was 5 for 16 cases, 4 for 2 cases, 3 for 2 cases, and 1 for 1 case. GOS outcomes at 6 months were better for endovascularly treated patients (p = 0.047). Conclusion: Results showed better outcomes for the endovascular treatment group compared to microsurgical clipping at 6 months after surgery. The anatomical classification of aneurysms in this region may be of help to develop effective treatment strategies.

Chronic prostatitis/chronic pelvic pain syndrome induces metabolomic changes in expressed prostatic secretions and plasma.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.

Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

WSe2 Negative Capacitance Field-Effect Transistor for Biosensing Applications.

Field-effect transistor (FET) biosensors based on two-dimensional (2D) materials are highly sought after for their high sensitivity, label-free detection, fast response, and ease of on-chip integration. However, the subthreshold swing (SS) of FETs is constrained by the Boltzmann limit and cannot fall below 60 mV/dec, hindering sensor sensitivity enhancement. Additionally, the gate-leakage current of 2D material biosensors in liquid environments significantly increases, adversely affecting the detection accuracy and stability. Based on the principle of negative capacitance, this paper presents for the first time a two-dimensional material WSe2 negative capacitance field-effect transistor (NCFET) with a minimum subthreshold swing of 56 mV/dec in aqueous solution. The NCFET shows a significantly improved biosensor function. The pH detection sensitivity of the NCFET biosensor reaches 994 pH-1, nearly an order of magnitude higher than that of the traditional two-dimensional WSe2 FET biosensor. The Al2O3/HfZrO (HZO) bilayer dielectric in the NCFET not only contributes to negative capacitance characteristics in solution but also significantly reduces the leakage in solution. Utilizing an enzyme catalysis method, the WSe2 NCFET biosensor demonstrates a specific detection of glucose molecules, achieving a high sensitivity of 4800 A/A in a 5 mM glucose solution and a low detection limit (10-9 M). Further experiments also exhibit the ability of the biosensor to detect glucose in sweat.

Global diversity and ecological functions of viruses inhabiting oil reservoirs.

Oil reservoirs, being one of the significant subsurface repositories of energy and carbon, host diverse microbial communities affecting energy production and carbon emissions. Viruses play crucial roles in the ecology of microbiomes, however, their distribution and ecological significance in oil reservoirs remain undetermined. Here, we assemble a catalogue encompassing viral and prokaryotic genomes sourced from oil reservoirs. The catalogue comprises 7229 prokaryotic genomes and 3,886 viral Operational Taxonomic Units (vOTUs) from 182 oil reservoir metagenomes. The results show that viruses are widely distributed in oil reservoirs, and 85% vOTUs in oil reservoir are detected in less than 10% of the samples, highlighting the heterogeneous nature of viral communities within oil reservoirs. Through combined microcosm enrichment experiments and bioinformatics analysis, we validate the ecological roles of viruses in regulating the community structure of sulfate reducing microorganisms, primarily through a virulent lifestyle. Taken together, this study uncovers a rich diversity of viruses and their ecological functions within oil reservoirs, offering a comprehensive understanding of the role of viral communities in the biogeochemical cycles of the deep biosphere.

Oxytocin Protects Nigrostriatal Dopamine Signal via Activating GABAergic Circuit in the MPTP-Induced Parkinson's Disease Model.

The most pronounced neuropathological feature of Parkinson's disease (PD) is the loss of dopamine (DA) neurons in the substantia nigra compacta (SNc), which depletes striatal DA. Hypothalamic oxytocin is found to be reduced in PD patients and closely interacts with the DA system, but the role of oxytocin in PD remains unclear. Here, the disturbances of endogenous oxytocin level and the substantia nigra (SN) oxytocin receptor expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model is observed, correlated with the striatal tyrosine hydroxylase (TH) expression reduction. Killing/silencing hypothalamic oxytocin neurons aggravates the vulnerability of nigrostriatal DA signal to MPTP, whereas elevating oxytocin level by intranasal delivery or microinjecting into the SN promotes the resistance. In addition, knocking out SN oxytocin receptors induces the time-dependent reductions of SNc DA neurons, striatal TH expression, and striatal DA level by increasing neuronal excitotoxicity. These results further uncover that oxytocin dampens the excitatory synaptic inputs onto DA neurons via activating oxytocin receptor-expressed SN GABA neurons, which target GABA(B) receptors expressed in SNc DA neuron-projecting glutamatergic axons, to reduce excitotoxicity. Thus, besides the well-known prosocial effect, oxytocin acts as a key endogenous factor in protecting the nigrostriatal DA system.

Zelquistinel acts at an extracellular binding domain to modulate intracellular calcium inactivation of N-methyl-d-aspartate receptors.

Stinels are a novel class of N-methyl-d-aspartate glutamate receptor (NMDAR) positive allosteric modulators. We explored mechanism of action and NR2 subtype specificity of the stinel zelquistinel (ZEL) in HEK 293 cells expressing recombinant NMDARs. ZEL potently enhanced NMDAR current at NR2A (EC50 = 9.9 ± 0.5 nM) and NR2C-containing (EC50 = 9.7 ± 0.6 nM) NMDARs, with a larger ceiling enhancement at NR2B-NMDAR (EC50 = 35.0 ± 0.7 nM), while not affecting NR2D-containing NMDARs. In cells expressing NR2A and NR2C-containing NMDARs, ZEL exhibited an inverted-U dose-response relation, with a low concentration enhancement and high concentration suppression of NMDAR currents. Extracellular application of ZEL potentiated NMDAR receptor activity via prolongation of NMDAR currents. Replacing the slow Ca2+ intracellular chelator EGTA with the fast chelator BAPTA blocked ZEL potentiation of NMDARs, suggesting an action on intracellular Ca2+-calmodulin-dependent inactivation (CDI). Consistent with this mechanism of action, removal of the NR1 intracellular C-terminus, or intracellular infusion of a calmodulin blocking peptide, blocked ZEL potentiation of NMDAR current. In contrast, BAPTA did not prevent high-dose suppression of current, indicating this effect has a different mechanism of action. These data indicate ZEL is a novel positive allosteric modulator that binds extracellularly and acts through a unique long-distance mechanism to reduce NMDAR CDI, eliciting enhancement of NMDAR current. The critical role that NMDARs play in long-term, activity-dependent synaptic plasticity, learning, memory and cognition, suggests dysregulation of CDI may contribute to psychiatric disorders such as depression, schizophrenia and others, and that the stinel class of drugs can restore NMDAR-dependent synaptic plasticity by reducing activity-dependent CDI.