Oral oxytocin blurs sex differences in amygdala responses to emotional scenes.

BACKGROUND: The sex differences were co-shaped by innate biological differences and social environment, and were frequently observed in human emotional neural responses. Oral administration of oxytocin, as an alternative and noninvasive intake method, has been demonstrated to produce sex-dependent effects on emotional face processing. However, it is unclear whether oral oxytocin produces similar sex-dependent effects on processing continuous emotional scenes. METHODS: Current randomized, double-blind, placebo-controlled neuro-psychopharmacological fMRI experiment was conducted in 147 healthy participants (oxytocin=74, male/female=37/37; placebo=73, male/female=36/37) to examine the oral oxytocin effect on plasma oxytocin concentrations and neural response to emotional scenes in both sexes. RESULTS: At the neuroendocrine level, females showed lower endogenous oxytocin concentrations than males, but oral oxytocin equally increased the oxytocin concentrations in both sexes. Regarding neural activity, emotional scenes evoked opposite valence-independent effects on right amygdala activation (females>males) and its functional connectivity with the insula (males>females) in two sexes in the placebo group. This sex difference were either attenuated (amygdala response) or even completely eliminated (amygdala-insula functional connectivity) in the oxytocin group. The multivariate pattern analysis confirmed these findings by developing an accurate sex-predictive neural pattern that including the amygdala and the insula under the placebo but not oxytocin condition. CONCLUSION: Present study suggests a pronounced sex-difference in neural responses to emotional scenes which is abolished by oral oxytocin, with it having opposite modulatory effects in two sexes. Possibly this may reflect oral OXT enhancing emotional regulation to continuous emotional stimuli in both sexes by facilitating appropriate changes in sex-specific amygdala-insula circuitry.

An approach for estimating microbial growth and chlorinated ethenes biotransformation in groundwater based on discrete observations.

The bioremediation of chlorinated ethenes (CEs) contaminated groundwater is attracting increasingly attention in practical remediation projects. However, modelling of microbial metabolic processes under the constraints of substrate and environmental factors is inadequate. This study developed a new kinetic model, which incorporated the logistic model and Dual-Monod kinetic to represent the interaction between the controlled microbial growth and the bioavailable substrates in CE-contaminated groundwater. The proposed model was based on discrete observations to simulate microbial growth under the constraints of substrate and environmental conditions, reducing the amount of observational data required for the model. Meanwhile, the proposed model introduced two new kinetic parameters, the effective specific growth rate µeff and the real self-limiting coefficient of microbial growth keff,sl, to simplified the number of independent parameters. A parameter estimation method based on the quasi-Newton's algorithm for the proposed model was also developed. The model was validated based on the hypothetical data, experimental results, and a published dataset, demonstrated the successful simulation of microbial growth and the sequential biodegradation of PCE in groundwater systems (*E < 0.3). The monitoring duration and the sampling schedule have significant impacts on estimating the biological parameters, and large errors would be induced when the data from the periods of extremely low substrate concentration or microbial growth decline were involved in parameter estimation. The research suggested that the proposed kinetic model provided a new insight to express the limitation of microbial population growth due to the available substrates and environmental factors, and is hoping to be applied in actual CE-contaminated sites.

Effectiveness of transforaminal approach spinal endoscopy in the treatment of patients with lumbar disc herniation and the factors affecting its efficacy.

OBJECTIVE: To compare the surgical metrics, improvement of functional scores, and clinical efficacy of percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) and to analyze the independent risk factors affecting the therapeutic efficacy of PETD. METHODS: The clinical data of LDH (lumbar disc herniation) patients who underwent treatment in Shaanxi Provincial Nuclear Industry 215 Hospital from May 2020 to May 2022 were retrospectively collected, including 70 PEID cases and 74 PETD cases. The two groups were compared in terms of surgical indexes, such as operation time and bleeding volume, as well as changes in functional scores, such as preoperative and postoperative Visual Analogue Scale (VAS) scores and Oswestry Disability Index (ODI). The clinical efficacy was evaluated according to the Macnab criteria, and logistic regression analysis was performed to determine the independent influencing factors of the treatment efficacy of PETD. RESULTS: The differences between the two surgical groups were statistically significant in terms of operation time (P<0.001), bleeding (P=0.005), and C-arm X-ray exposure times (P<0.001), and the above indexes were higher in the PETD group; however, there were no statistical differences in terms of improvement in functional scores (P>0.05) and clinical efficacy (P>0.05) between the two groups. BMI≥25 kg/m2 (P=0.001), severe disc degeneration (P=0.003), and operation time ≥60 min (P=0.003), severe disc degeneration (P=0.003), and operation time ≥60 min (P=0.036) were independent risk factors for the outcome of PETD. CONCLUSION: The clinical effectiveness of PEID and PETD in treating LDH is comparable, and each has its own advantages. While PETD is more technically demanding, it does not yield superior results. Obesity, severe disc degeneration, and prolonged surgery are risk factors for the treatment efficacy of PETD.

Fascicular Substrate Modification to Treat Human Ventricular Fibrillation.

BACKGROUND: Purkinje fibers play an important role in initiation and maintenance of ventricular fibrillation (VF) and polymorphic ventricular tachycardia (PMVT). Fascicular substrate modification (FSM) approaches have been suggested to treat recurrent VF in case reports and small case series. OBJECTIVES: The aim of this study was to investigate outcomes of catheter-based FSM to treat VF and PMVT. METHODS: Of 2,212 consecutive patients with ventricular arrhythmia undergoing catheter ablation, 18 (0.81%) underwent FSM of the Purkinje fibers as identified with high-density mapping during sinus rhythm. Fascicular substrate and VF initiation were mapped using a multipolar catheter. The endpoint of the ablation was noninducibility of VF and PMVT. In select patients, remapping revealed elimination of the targeted Purkinje potentials. Demographic, clinical, and follow-up characteristics were prospectively collected in our institutional database. RESULTS: A total of 18 patients (mean age 56 ± 3.8 years, 22% women) were included in the study. Of those, 11 (61.1%) had idiopathic VF, 3 (16.7%) had nonischemic cardiomyopathy, and 4 (22.2%) had mixed cardiomyopathy. The average left ventricular ejection fraction was 42.5%. At least 2 antiarrhythmic drugs had failed preablation. At baseline, all patients had inducible VF or PMVT. At the end of the procedure, no patient demonstrated new evidence of fascicular block or bundle branch block. There were no procedure-related complications. After a median follow-up period of 24 months, 16 patients (88.9%) were arrhythmia free on or off drugs: 11 of 11 patients (100%) with idiopathic VF vs 5 of 7 patients (71.4%) with underlying cardiomyopathy (P = 0.06). CONCLUSIONS: Catheter ablation of human VF and PMVT with FSM is feasible and safe and appears highly effective, with high rates of acute VF noninducibility and long-term freedom from recurrent VF.

Probiotics relieve perioperative postoperative cognitive dysfunction induced by cardiopulmonary bypass through the kynurenine metabolic pathway.

Postoperative cognitive dysfunction (POCD) has become the popular critical post-operative consequences, especially cardiopulmonary bypass surgery, leading to an increased risk of mortality. However, no therapeutic effect about POCD. Probiotics are beneficial bacteria living in the gut and help to reduce the risk of POCD. However, the detailed mechanism is still not entirely known. Therefore, our research aims to uncover the effect and mechanism of probiotics in relieving POCD and to figure out the possible relationship between kynurenine metabolic pathway. 36 rats were grouped into three groups: sham operated group (S group, n = 12), Cardiopulmonary bypass group (CPB group, n = 12), and probiotics+CPB (P group, n = 12). After CPB model preparation, water maze test and Garcia score scale was performed to identify the neurological function. Immunofluorescence and Hematoxylin and eosin staining has been used for hippocampal neurons detection. Brain injury related proteins, oxidative stress factors, and inflammatory factors were detected using enzyme-linked immunosorbent assays (ELISA). Neuronal apoptosis was detected by TdT-mediated dUTP nick end-labeling (TUNEL) staining and western blot. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was performed to detect the key factors of the kynurenine metabolic pathway. Our results demonstrated that probiotics improved neurological function of post-CPB rats. The administration of probiotics ameliorated memory and learning in spatial terms CPB rats (P < 0.05). Hematoxylin and eosin (H&E) staining data, S-100ß and neuron-specific enolase (NSE) data convinced that probiotics agonists reduced brain damage in CPB rats (P < 0.05). Moreover, probiotics regulated inflammatory factors, meanwhile attenuated hippocampal neuronal apoptosis. Probiotics alleviated POCD in rats with CPB through regulation of kynurenine metabolic signaling pathway.

Gp85 protein encapsulated by alginate-chitosan composite microspheres induced strong immunogenicity against avian leukosis virus in chicken.

Introduction: Avian leukosis, a viral disease affecting birds such as chickens, presents significant challenges in poultry farming due to tumor formation, decreased egg production, and increased mortality. Despite the absence of a commercial vaccine, avian leukosis virus (ALV) infections have been extensively documented, resulting in substantial economic losses in the poultry industry. This study aimed to develop alginate-chitosan composite microspheres loaded with ALV-J Gp85 protein (referred to as aCHP-gp85) as a potential vaccine candidate. Methods: Sodium alginate and chitosan were utilized as encapsulating materials, with the ALV-J Gp85 protein serving as the active ingredient. The study involved 45 specific pathogen-free (SPF) chickens to evaluate the immunological effectiveness of aCHP-gp85 compared to a traditional Freund adjuvant-gp85 vaccine (Freund-gp85). Two rounds of vaccination were administered, and antibody levels, mRNA expression of immune markers, splenic lymphocyte proliferation, and immune response were assessed. An animal challenge experiment was conducted to evaluate the vaccine's efficacy in reducing ALV-J virus presence and improving clinical conditions. Results: The results demonstrated that aCHP-gp85 induced a significant and sustained increase in antibody levels compared to Freund-gp85, with the elevated response lasting for 84 days. Furthermore, aCHP-gp85 significantly upregulated mRNA expression levels of key immune markers, notably TNF-α and IFN-γ. The application of ALV-J Gp85 protein within the aCHP-gp85 group led to a significant increase in splenic lymphocyte proliferation and immune response. In the animal challenge experiment, aCHP-gp85 effectively reduced ALV-J virus presence and improved clinical conditions compared to other groups, with no significant pathological changes observed. Discussion: The findings suggest that aCHP-gp85 elicits a strong and prolonged immune response compared to Freund-gp85, indicating its potential as an innovative ALV-J vaccine candidate. These results provide valuable insights for addressing avian leukosis in the poultry industry, both academically and practically.

Ethyl 2-[(2-oxo-2H-chromen-6-yl)-oxy]acetate.

Ethyl 2-[(2-oxo-2H-chromen-6-yl)-oxy]acetate, C13H12O5, a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C2/c space group in the form of sheets, within which mol-ecules are related by inversion centers and 21 axes. Multiple C-H⋯O weak hydrogen-bonding inter-actions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Inter-sheet inter-actions are a combination of coumarin system π-π stacking and additional C-H⋯O weak hydrogen bonds between ethyl acet-oxy groups.

Nanobody-Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING-Mediated Anti-Tumor Immunity.

Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non-pathogenic bacteria carry potential risks due to their non-specific targeting effects, and their anti-tumor activity is limited when used as monotherapy. In this study, a biohybrid-engineered bacterial system comprising non-pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17-positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria-mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD-1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor-specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low-immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages.

A Nomogram Based on Conventional Ultrasound Radiomics for Differentiating Between Radial Scar and Invasive Ductal Carcinoma of the Breast.

ABSTRACT: We aimed to develop and validate a nomogram based on conventional ultrasound (CUS) radiomics model to differentiate radial scar (RS) from invasive ductal carcinoma (IDC) of the breast. In total, 208 patients with histopathologically diagnosed RS or IDC of the breast were enrolled. They were randomly divided in a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Overall, 1316 radiomics features were extracted from CUS images. Then a radiomics score was constructed by filtering unstable features and using the maximum relevance minimum redundancy algorithm and the least absolute shrinkage and selection operator logistic regression algorithm. Two models were developed using data from the training cohort: one using clinical and CUS characteristics (Clin + CUS model) and one using clinical information, CUS characteristics, and the radiomics score (radiomics model). The usefulness of nomogram was assessed based on their differentiating ability and clinical utility. Nine features from CUS images were used to build the radiomics score. The radiomics nomogram showed a favorable predictive value for differentiating RS from IDC, with areas under the curve of 0.953 and 0.922 for the training and validation cohorts, respectively. Decision curve analysis indicated that this model outperformed the Clin + CUS model and the radiomics score in terms of clinical usefulness. The results of this study may provide a novel method for noninvasively distinguish RS from IDC.

A single-frame deflectometry method for online inspection of light-transmitting components.

Transparent materials are widely used in industrial applications, such as construction, transportation, and optics. However, the complex optical properties of these materials make it difficult to achieve precise surface form measurements, especially for bulk surface form inspection in industrial environments. Traditional structured light-based measurement methods often struggle with suboptimal signal-to-noise ratios, making them ineffective. Currently, there is a lack of efficient techniques for real-time inspection of such components. This paper proposes a single-frame measurement technique based on deflectometry for large-size transparent surfaces. It utilizes the reflective characteristics of the measured surface, making it independent of the surface's diffuse reflection properties. This fundamentally solves the issues associated with signal-to-noise ratios. By discretizing the phase map, it separates the multiple surface reflection characteristics of transparent devices, enabling transparent device measurement. To meet the requirements of industrial dynamic measurement, this technique only needs a simple and low-cost system structure, which contains just two cameras for image capture. It does not require phase shifting to complete the measurement, making it independent of the screen and having the potential for larger surface measurement. The proposed method was used to measure a 400mm aperture automobile glass, and the results showed that it is able to achieve a measurement accuracy on the order of 10 µm. The method proposed in this paper overcomes the influence of surface reflection on transparent objects and significantly improves the efficiency and accuracy of large-sized transparent surface measurements by using a single-frame image measurement. Moreover, this method shows promise for broader applications, including measurements of lenses and HUD (Heads-Up Display) components, showcasing significant potential for industrial applications.

Association between urate-lowering therapy initiation and all-cause mortality in patients with type 2 diabetes and asymptomatic hyperuricemia.

AIMS: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 µmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 µmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 µmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship. CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 µmol/L could potentially enhance this reduced mortality.

The association between socioeconomic status perception and mental health among Chinese older adults: the mediating roles of social trust and justice.

BACKGROUND: Mental health is a matter of quality of life among older adults. This study aimed to explore the association between the socioeconomic status (SES) perception and mental health of older adults using data from 2017 Chinese General Social Survey (CGSS). METHODS: Ordinary least squares (OLS) regression was used to analyse the association between SES perception and mental health, and the substitution model and variable methods were used to check the robustness of the results. Moreover, we adopted the Sobel model to analyse the mediating roles of social trust and justice. RESULTS: SES perception was positively associated with mental health, and this association was mediated by social trust and justice. This kind of positive association was mainly embodied in those groups with the highest or lowest objective SES. In other words, this study confirmed the phenomenon of "a contented mind is a perpetual feast" in Chinese society. CONCLUSIONS: Higher SES perception is associated with improved mental health for Chinese older adults. It is imperative to prioritize efforts to enhance the perceptual abilities of older adults, particularly those with the highest or lowest objective SES, to promote their overall subjective well-being.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

High Stability and Corrosion-Resistant Gas of Recyclable and Versatile Manganese-Doped Lead-Free Double Perovskite Crystals toward Novel Functional Fabric and Photoelectric Device.

Lead-free halide perovskites possess excellent photoelectric properties, making them widely used in the photoelectric fields. Herein, lead-free double perovskite crystals (PCs) doped with manganese (Cs2NaInCl6:Mn2+) are successfully prepared by the more energy-efficient crystallization method. The crystals emit bright orange-red light under the ultraviolet (UV) lamp, showing unique optical properties. They have the highest photoluminescence quantum yield of 42.91%. The white light-emitting diodes (LEDs) are fabricated using these perovskite crystals, which show a color rendering index of 92 and external quantum efficiency (EQE) as high as 16.3%. Furtherly, perovskite-modified fiber paper made of aramid chopped fibers (ACFs) and polyphenylene sulfide (PPS) exhibited fluorescent properties under different conditions. This paper combines fiber composite technology with PPS fiber filter bags, which are widely used in environmental protection, for the first time and demonstrates functional fiber filter bags with fluorescent characteristics. This filter bag provides an idea for the automatic detection of industrial filtration. Meanwhile, after being exposed to industrial waste gas for 60 h, the filter bag can maintain superior fluorescence performance. In this study, lead-free double perovskites are synthesized using an efficient method for preparing high-performance LEDs and high-stability fluorescent fibers. Concurrently, the application of perovskites in environmental protection is expanded.

Incidence, risk factors, and outcomes of acute liver injury in hospitalized adults with acute kidney injury: a large multicenter study.

BACKGROUND: Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes. METHODS: The study population included patients aged 18-99 years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality. RESULTS: Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037). CONCLUSIONS: ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

NIR-II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy.

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.

Non-flooding conditions caused by water table drawdown alter microbial network complexity and decrease multifunctionality in alpine wetland soils.

Several soil functions of alpine wetland depend on microbial communities, including carbon storage and nutrient cycling, and soil microbes are highly sensitive to hydrological conditions. Wetland degradation is often accompanied by a decline in water table. With the water table drawdown, the effects of microbial network complexity on various soil functions remain insufficiently understood. In this research, we quantified soil multifunctionality of flooded and non-flooded sites in the Lalu Wetland on the Tibetan Plateau. We employed high-throughput sequencing to investigate the microbial community responses to water table depth changes, as well as the relationships between microbial network properties and soil multifunctionality. Our findings revealed a substantial reduction in soil multifunctionality at both surface and subsurface soil layers (0-20 cm and 20-40 cm) in non-flooded sites compared to flooded sites. The α-diversity of bacteria in the surface soil of non-flooded sites was significantly lower than that in flooded sites. Microbial network properties (including the number of nodes, number of edges, average degree, density, and modularity of co-occurrence networks) exhibited significant correlations with soil multifunctionality. This study underscores the adverse impact of non-flooded conditions resulting from water table drawdown on soil multifunctionality in alpine wetland soils, driven by alterations in microbial community structure. Additionally, we identified soil pH and moisture content as pivotal abiotic factors influencing soil multifunctionality, with microbial network complexity emerging as a valuable predictor of multifunctionality.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Reliable wafer-scale integration of two-dimensional materials and metal electrodes with van der Waals contacts.

Since the first report on single-layer MoS2 based transistor, rapid progress has been achieved in two-dimensional (2D) material-based atomically thin electronics, providing an alternative approach to solve the bottleneck in silicon device miniaturization. In this scenario, reliable contact between the metal electrodes and the subnanometer-thick 2D materials becomes crucial in determining the device performance. Here, utilizing the quasi-van der Waals (vdW) epitaxy of metals on fluorophlogopite mica, we demonstrate an all-stacking method for the fabrication of 2D devices with high-quality vdW contacts by mechanically transferring pre-deposited metal electrodes. This technique is applicable for complex device integration with sizes up to the wafer scale and is also capable of tuning the electric characteristics of the interfacial junctions by transferring selective metals. Our results provide an efficient, scalable, and low-cost technique for 2D electronics, allowing high-density device integration as well as a handy tool for fundamental research in vdW materials.