Picolinic acid-mediated Mn(II) activated periodate for ultrafast and selective degradation of emerging contaminants: Key role of high-valent Mn-oxo species.

The utilization of periodate (PI, IO4-) in metal-based advanced oxidation processes (AOPs) for the elimination of emerging contaminants (ECs) have garnered significant attention. However, the commonly used homogeneous metal catalyst Mn(II) performs inadequately in activating PI. Herein, we exploited a novel AOP technology by employing the complex of Mn(II) with the biodegradable picolinic acid (PICA) to activate PI for the degradation of electron-rich pollutants. The performance of the Mn(II)-PICA complex surpassed that of ligand-free Mn(II) and other Mn(II) complexes with common aminopolycarboxylate ligands. Through scavenger, sulfoxide-probe transformation, and 18O isotope-labeling experiments, we confirmed that the dominant reactive oxidant generated in the Mn(II)-PICA/PI system was high-valent manganese-oxo species (Mn(V)=O). Due to its reliance on Mn(V)=O, the Mn(II)-PICA/PI process exhibited remarkable selectivity and strong anti-interference during EC oxidation in complex water matrices. Nine structurally diverse pollutants were selected for evaluation, and their lnkobs values in the Mn(II)-PICA/PI system correlated well with their electrophilic/nucleophilic indexes, EHOMO, and vertical IP (R2 = 0.79-0.94). Additionally, IO4- was converted into non-toxic iodate (IO3-) without producing undesired iodine species such as HOI, I2, and I3-. This study provides a novel protocol for metal-based AOPs using PI in combination with chelating agents and high-valent metal-oxo species formation during water purification.

Simultaneously Controlling Inflammation and Infection by Smart Nanomedicine Responding to the Inflammatory Microenvironment.

The overactivated immune cells in the infectious lesion may lead to irreversible organ damages under severe infections. However, clinically used immunosuppressive anti-inflammatory drugs will usually disturb immune homeostasis and conversely increase the risk of infections. Regulating the balance between anti-inflammation and anti-infection is thus critical in treating certain infectious diseases. Herein, considering that hydrogen peroxide (H2O2), myeloperoxidase (MPO), and neutrophils are upregulated in the inflammatory microenvironment and closely related to the severity of appendectomy patients, an inflammatory-microenvironment-responsive nanomedicine is designed by using poly(lactic-co-glycolic) acid (PLGA) nanoparticles to load chlorine E6 (Ce6), a photosensitizer, and luminal (Lum), a chemiluminescent agent. The obtained Lum/Ce6@PLGA nanoparticles, being non-toxic within normal physiological environment, can generate cytotoxic single oxygen via bioluminescence resonance energy transfer (BRET) in the inflammatory microenvironment with upregulated H2O2 and MPO, simultaneously killing pathogens and excessive inflammatory immune cells in the lesion, without disturbing immune homeostasis. As evidenced in various clinically relevant bacterial infection models and virus-induced pneumonia, Lum/Ce6@PLGA nanoparticles appeared to be rather effective in controlling both infection and inflammation, resulting in significantly improved animal survival. Therefore, the BRET-based nanoparticles by simultaneously controlling infections and inflammation may be promising nano-therapeutics for treatment of severe infectious diseases.

Nanofluidic Thermoelectric Transducer with Ultrahigh and Tunable Sensitivity.

Thermosensitive transient receptor potential (thermoTRP) ion channels can transduce external thermal stimuli to neural electrical signals, allowing organisms to detect and respond to changes in environmental temperature. Reproducing such ionic machinery holds promise for advancing the design of highly efficient low-grade thermal energy harvesters and ultrasensitive thermal sensors. However, there still exist challenges for artificial nanofluidic architectures to achieve comparable thermoelectric performance. Here, we report nanofluidic thermoelectric transducers with ultrahigh and tunable sensitivities controlled by electrostatic gating in graphene nanochannels. The equivalent Seebeck coefficient can be significantly boosted and reaches 1 order of magnitude higher than the current state of the art, even beyond thermoTRP ion channels. The improvement is attributed to substantial slippage on the highly charged graphene surface, leading to enhanced electrokinetic ion transport inside the graphene channel, which is confirmed by a scaling theory for thermoelectric coupling as well as molecular dynamic simulations. The dependence of the nanofluidic thermoelectric on the concentration, channel size, and cation types is also investigated to further clarify the underlying mechanism.

Exploration of the association between new "Life's Essential 8" with hyperuricemia and gout among US adults.

BACKGROUND: Previous researches have reported the relationship between uric acid and cardiovascular disease. We aimed to investigate the association of Life's Essential 8, a recently updated measurement of cardiovascular health, with the prevalence of hyperuricemia (HUA) and gout among US adults. Additionally, we also explored the relationship between LE8 and all-cause mortality among patients with HUA or gout. METHODS: Participants from the National Health and Nutrition Examination Survey in 2007-2016 were involved in this study. LE8 score was categorized into low, moderate, high CVH groups according to American Heart Association definitions. Multivariable logistic regression and cox regression analyses, restricted cubic spline models, subgroup analysis and sensitivity analysis were used to explore the associations. RESULTS: A total of 23,619 adult participants were included in this study, which included 4,775 hyperuricemia patients and 1,055 gout patients. Among all participants, the overall median LE8 score was 65.62 (21.25) and the prevalence of hyperuricemia and gout of were 20.2% and 4.5%, respectively. After fully adjusted the potential confounders, participants in high CVH group had a lower prevalence of hyperuricemia and gout compared with the low CVH group, with a OR (95%CI) of 0.50 (0.39-0.63) and 0.50 (0.30-0.82), respectively. The restricted cubic spline showed a significantly inverse relationship between LE8 and hyperuricemia and gout. Similar patterns were also identified in the association between LE8 scores and all-cause mortality in HUA and gout patients. CONCLUSIONS: Higher LE8 scores are associated with lower risk and lower all-cause mortality of HUA and gout among US adults. Adherence to optimal CVH metrics may be an appropriate prevention and management strategy for reducing the socioeconomic burden of hyperuricemia and gout.

Efficacy and prognostic factors of COVID-19 vaccine in patients with hepatocellular carcinoma: Analysis of data from a prospective cohort study.

BACKGROUND: The efficacy of coronavirus disease 2019 (COVID-19) vaccines in preventing SARS-CoV-2 infection in patients with hepatocellular carcinoma (HCC) is not clear. METHODS: From January 2022 to October 2022, patients diagnosed with HCC in a prospective, multicenter, observational cohort were analyzed. RESULTS: One hundred and forty-one patients with (n = 107) or without COVID-19 vaccination (n = 34) were included. The number of patients with severe or very severe infection was relatively lower in the vaccinated group (3.7% vs. 11.8%, p = 0.096). Median infection-free survival in the vaccinated group (14.0 vs. 8.3 months, p = 0.010) was significantly longer than that in the unvaccinated group. COVID-19 vaccination (hazard ratio (HR) HR = 0.47), European Cooperative Oncology Group performance score = 0 (HR = 2.06), and extrahepatic spread (HR = 0.28) were found to be the independent predictive factors for infection-free survival. CONCLUSION: COVID-19 vaccines could effectively reduce the SARS-Cov-2 infection in patients with HCC.

Integrated Comparative Transcriptome and Weighted Gene Co-Expression Network Analysis Provide Valuable Insights into the Mechanisms of Pinhead Initiation in Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota).

The initiation and formation of the "pinhead" is the key node in growth process of Ophiocordyceps sinensis (Chinese Cordyceps). The research on the mechanism of changes in this growth stage is the basis for realizing the industrialization of its artificial cultivation. Clarifying the mechanisms of pinhead initiation is essential for its further application. Here, we performed a comprehensive transcriptome analysis of pinhead initiation process in O. sinensis. Comparative transcriptome analysis revealed remarkable variation in gene expression and enriched pathways at different pinhead initiation stages. Gene co-expression network analysis by WGCNA identified 4 modules highly relevant to different pinhead initiation stages, and 23 hub genes. The biological function analysis and hub gene annotation of these identified modules demonstrated that transmembrane transport and nucleotide excision repair were the topmost enriched in pre-pinhead initiation stage, carbohydrate metabolism and protein glycosylation were specially enriched in pinhead initiation stage, nucleotide binding and DNA metabolic process were over-represented after pinhead stage. These key regulators are mainly involved in carbohydrate metabolism, synthesis of proteins and nucleic acids. This work excavated the candidate pathways and hub genes related to the pinhead initiation stage, which will serve as a reference for realizing the industrialization of artificial cultivation in O. sinensis.

Geniposide modulates GSK3ß to inhibit Th17 differentiation and mitigate endothelial damage in intracranial aneurysm.

Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3ß in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3ß/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF-α and IL-23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen-treated, Th17 differentiation-inducing cell-conditioned medium significantly up-regulated the expression of tight junction proteins ZO-1, Occludin, and Claudin-5 in murine aortic endothelial cells. Administering the GSK3ß inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up-regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3ß, which reduces endothelial cell injury and up-regulates tight junction protein expression.

Cervical Vertebra Bone Quality Score Predicts Zero-Profile Anchored Spacer Interbody Fusion Cage Subsidence after Anterior Cervical Diskectomy and Fusion: A Retrospective Study.

STUDY DESIGN: Retrospective study. OBJECTIVE: This retrospective study primary focus is to investigate the relationship between the C-VBQ score and the occurrence of postoperative zero-profile anchored spacer (ROI-C) interbody fusion cage subsidence. Additionally, we aim to evaluate the predictive efficacy of the C-VBQ scoring system for subsidence in the context of ACDF with the ROI-C. METHODS: Patients who underwent ACDF with the ROI-C cage at our hospital between January 2016 and December 2022 were included in this study. Univariate analysis and multivariate logistic regression were employed to identify independent risk factors associated with ROI-C cage subsidence after ACDF. Pearson correlation analysis was utilized to assess the correlation between the C-VBQ score and the height of ROI-C cage subsidence. RESULTS: A total of 102 patients underwent ACDF with ROI-C in our hospital were included in this study. Univariate analysis showed that age (P = 0.021) and C-VBQ score (P < 0.001) were the influencing factors of cage subsidence. Pearson correlation analysis showed that there was a significant positive correlation between the subsidence height of ROI-C cage and C-VBQ (r = 0.55, P < 0.01). Multivariate binary logistic regression analysis showed that C-VBQ score was the only variable that could significantly predict the subsidence of ROI-C cage after ACDF. Higher C-VBQ score was significantly associated with cage subsidence (P < 0.001).The AUC was 0.89, and the cutoff value for C-VBQ was 2.70. CONCLUSION: The findings indicate a significant correlation between a higher C-VBQ score before surgery and ROI-C cage subsidence after ACDF. The preoperative assessment of C-VBQ proves valuable for clinicians, enabling them to identify patients with low bone mineral density and predict the risk of zero-profile anchored spacer interbody fusion cage subsidence following ACDF.

Multiple-stimuli fluorescent responsive metallo-organic helicated cage arising from monomer and excimer emission.

Effectively regulating monomer and excimer emission in a singular supramolecular luminous platform is challenging due to high difficulty of precise control over its aggregation and dispersion behavior when subjected to external stimuli. Here, we show a metallo-cage (MTH) featuring a triple helical motif that displays a unique dual emission. It arises from both intramolecular monomer and intermolecular excimer, respectively. The distorted molecular conformation and the staggered stacking mode of MTH excimer are verified through single crystal X-ray diffraction analysis. These structural features facilitate the switch between monomer and excimer emission, which are induced by changes in concentration and temperature. Significantly, adjusting the equilibrium between these two states in MTH enables the production of vibrant white light emission in both solution and solid state. Moreover, when combined with a PMMA (polymethyl methacrylate) substrate, the resulting thin films can serve as straightforward fluorescence thermometer and thermally activated information encryption materials.

Enhancing reductive dechlorination of trichloroethylene in bioelectrochemical systems with conductive materials.

The incorporation of conductive materials to enhance electron transfer in bioelectrochemical systems (BES) is considered a promising approach. However, the specific effects and mechanisms of these materials on trichloroethylene (TCE) reductive dechlorination in BES remains are not fully understood. This study investigated the use of magnetite nanoparticles (MNP) and biochars (BC) as coatings on biocathodes for TCE reduction. Results demonstrated that the average dechlorination rates of MNP-Biocathode (122.89 µM Cl·d-1) and BC-Biocathode (102.88 µM Cl·d-1) were greatly higher than that of Biocathode (78.17 µM Cl·d-1). Based on MATLAB calculation, the dechlorination rate exhibited a more significantly increase in TCE-to-DCE step than the other dechlorination steps. Microbial community analyses revealed an increase in the relative abundance of electroactive and dechlorinating populations (e.g., Pseudomonas, Geobacter, and Desulfovibrio) in MNP-Biocathode and BC-Biocathode. Functional gene analysis via RT-qPCR showed the expression of dehalogenase (RDase) and direct electron transfer (DET) related genes was upregulated with the addition of MNP and BC. These findings suggest that conductive materials might accelerate reductive dechlorination by enhancing DET. The difference of physicochemical characteristics (e.g. particle size and specific surface area), electron transfer enhancement mechanism between MNP and BC as well as the reduction of Fe(III) by hydrogen may explain the superior dechlorination rate observed with MNP-Biocathode.

Therapeutic potential of fucoidan in central nervous system disorders: A systematic review.

Central nervous system (CNS) disorders have a complicated pathogenesis, and to date, no single mechanism can fully explain them. Most drugs used for CNS disorders primarily aim to manage symptoms and delay disease progression, and none have demonstrated any pathological reversal. Fucoidan is a safe, sulfated polysaccharide from seaweed that exhibits multiple pharmacological effects, and it is anticipated to be a novel treatment for CNS disorders. To assess the possible clinical uses of fucoidan, this review aims to provide an overview of its neuroprotective mechanism in both in vivo and in vitro CNS disease models, as well as its pharmacokinetics and safety. We included 39 articles on the pharmacology of fucoidan in CNS disorders. In vitro and in vivo experiments demonstrate that fucoidan has important roles in regulating lipid metabolism, enhancing the cholinergic system, maintaining the functional integrity of the blood-brain barrier and mitochondria, inhibiting inflammation, and attenuating oxidative stress and apoptosis, highlighting its potential for CNS disease treatment. Fucoidan has a protective effect against CNS disorders. With ongoing research on fucoidan, it is expected that a natural, highly effective, less toxic, and highly potent fucoidan-based drug or nutritional supplement targeting CNS diseases will be developed.

[Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery].

OBJECTIVE: To investigate the effect of Polyetheretherketone (PEEK) rod semi-rigid pedicle screw fixation system in lumbar spine non-fusion surgery. METHODS: A total of 74 patients with tow-level lumbar degenerative diseases who underwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group. In the PEEK rod group, there were 34 patients, including 13 males and 21 females, aged from 51 to 79 years old with an average of (62.4±6.8) years old;There were 1 patient of L1-L3 segments, 7 patients of L2-L4 segments, 20 patients of L3-L5 segments and 6 patients of L4-S1 segments. In the titanium rod group, there were 40 patients, including 17 males and 23 females, aged from 52 to 81 years old with an average of (65.2±7.3) years old;There were 3 patient of L1-L3 segments, 11 patients of L2-L4 segments, 19 patients of L3-L5 segments and 7 patients of L4-S1 segments. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage was recorded. The visual analogue scale (VAS) for low back pain and Oswestry disability index (ODI) were compared in preoperatively and postoperatively(3 months, 12 months and last follow-up) between two groups. The change of range of motion (ROM) was observed by flexion and extension x-ray of lumbar. RESULTS: All patients successfully completed the operation. The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6) months. The operative time (142.2±44.7) min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group [(160.7±57.3) min、(212.8±85.4) ml](P<0.05). There was no significant differences in postoperative drainage between the two groups (P>0.05). At the final follow-up visit, in PEEK group and titanium group VAS of low back pain[(0.8±0.4) points vs (1.0±0.5) points], VAS for leg pain [ (0.7±0.4) points vs (0.8±0.5) points] and ODI [(9.8±1.6)% vs (12.1±1.5)%] were compared with preoperative [ (5.8±1.1) points vs (6.0±1.1)points], [ (7.2±1.7) points vs (7.0±1.6) points], [(68.5±8.9)% vs(66.3±8.2)%] were significantly different(P<0.05). There was no significant difference in VAS scores between the two groups at each postoperative time point (P>0.05). At 3 months after surgery, there was no difference in ODI between the two groups (P>0.05). There were significant differences in ODI between PEEK group and titanium rod group at 12 months [(15.5±2.1)% vs (18.4±2.4)%] and at the last follow-up [(9.8±1.6)% vs (12.1±1.5)%] (P<0.05). The total range of motion (ROM) of lumbar decreased in both groups after surgery. At 12 months after surgery and the last follow-up, the PEEK group compared with the titanium rod group, the total range of motion of lumbar was statistically significant (P<0.05). The range of motion (ROM) of the fixed segments decreased in both groups after surgery. The ROM of the fixed segments in PEEK group decreased from (9.5±4.6)° to (4.1±1.9)° at the last follow-up (P<0.05), which in the titanium rod group was decreased from (9.8±4.3)°to (0.9±0.5)° at the last follow-up (P<0.05). The range of motion (ROM) of upper adjacent segment increased in both groups, there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up, (P<0.05). There was no screw loosening and broken rods in both groups during the follow-up period. CONCLUSION: The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment, showing comparable short-term clinical efficacy to titanium rod fusion. PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degenerative diseases, and its long-term efficacy needs further follow-up observation.

Clinical study on freehand of bicortical sacral screw fixation with the assistance of torque measurement device.

BACKGROUND: Sacral screw loosening is a typical complication after internal fixation surgery through the vertebral arch system. Bicortical fixation can successfully prevent screw loosening, and how improving the rate of bicortical fixation is a challenging clinical investigation. OBJECTIVE: To investigate the feasibility of improving the double corticality of sacral screws and the optimal fixation depth to achieve double cortical fixation by combining the torque measurement method with bare hands. METHODS: Ninety-seven cases of posterior lumbar internal fixation with pedicle root system were included in this study. Based on the tactile feedback of the surgeon indicating the expected penetration of the screw into the contralateral cortex of the sacrum, the screws were further rotated by 180°, 360°, or 720°, categorized into the bicortical 180° group, bicortical 360° group, and bicortical 720° group, respectively. Intraoperatively, the torque during screw insertion was recorded. Postoperatively, the rate of double-cortex engagement was evaluated at 7 days, and screw loosening was assessed at 1 year follow-up. RESULTS: The bicortical rates of the 180° group, 360° group, and 720° group were 66.13%, 91.18% and 93.75%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05).The rates of loosening of sacral screws in the 180° group, 360° group, and 720° group were 20.97%, 7.35% and 7.81%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05). The bicortical 360° group achieved a relatively satisfactory rate of dual cortical purchase while maintaining a lower rate of screw loosening. CONCLUSION: Manual insertion of sacral screws with the assistance of a torque measurement device can achieve a relatively satisfactory dual cortical purchase rate while reducing patient hospitalization costs.

Green Solvent γ-Valerolactone (GVL) Facilitates Photocatalytic C-H Bond Activation.

Solvents can significantly influence chemical reactions in condensed phases. Their critical properties are increasingly recognized in various research domains such as organic synthesis and biomass valorization. However, in semiconductor photocatalysis, solvents are primarily viewed as mediums for dissolving and diffusing substances, with their potential beneficial effects on photocatalytic conversions often overlooked. Additionally, common photocatalysis solvents like acetonitrile (ACN) pose serious safety and environmental concerns. In this study, we demonstrate that novel and safe green solvents, such as γ-valerolactone (GVL), can significantly enhance the performance of semiconductor photocatalysis for C-H bond activation. Non-specific solvent-solute interactions are the primary contributors to increased photocatalytic activity in the self-coupling of benzylic compounds. Specifically, GVL's large dielectric constant and high refractive index lower the energy barrier for the rate-determining C-H bond activation step, facilitating a faster coupling reaction. The versatility of GVL is further demonstrated in reactions with multiple reagents and in various oxidation and reduction photocatalytic systems beyond classic C-H bond activation. This work not only pioneers the use of green solvents but also provides comprehensive insights for proper solvent selection in semiconductor photocatalysis.

Phytochemicals targeting mitophagy: Therapeutic opportunities and prospects for treating Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder and the leading cause of age-related cognitive decline. Recent studies have established a close relationship between mitophagy and the pathogenesis of AD. Various phytochemicals have shown promising therapeutic effects in mitigating the onset and progression of AD. This review offers a comprehensive overview of the typical features of mitophagy and the underlying mechanisms leading to its occurrence in AD, highlighting its significance in the disease's pathogenesis and progression. Additionally, we examine the therapeutic mechanisms of synthetic drugs that induce mitophagy in AD. Finally, we summarize recent advances in research on phytochemicals that regulate mitophagy in the treatment of AD, potentially guiding the development of new anti-AD drugs.

Interconversion and functional composites of metal-organic frameworks and hydrogen-bonded organic frameworks.

Metal-organic frameworks (MOFs), an emerging class of highly ordered crystalline porous materials, possess structural tunability, high specific surface area, well-defined pores, and diverse pore environments and morphologies, making them suitable for various potential applications. Moreover, hydrogen-bonded organic frameworks (HOFs), constructed from organic molecules with complementary hydrogen-bonding patterns, are rapidly evolving into a novel category of porous materials due to their facile mild preparation conditions, solution processability, easy regeneration capability, and excellent biocompatibility. These distinctive advantages have garnered significant attention across diverse fields. Considering the inherent binding affinity between MOFs and HOFs along with the fact that many MOF linkers can serve as building blocks for constructing HOFs, their combination holds promise in creating functional materials with enhanced performance. This feature paper provides an introduction to the interconversion between MOFs and HOFs followed by highlighting the emerging applications of MOF-HOF composites. Finally, we briefly discuss the current challenges associated with future perspectives on MOF-HOF composites.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Hippocampal SorCS2 overexpression represses chronic stress-induced depressive-like behaviors by promoting the BDNF-TrkB system.

BACKGROUND: Emerging data has demonstrated that in mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Thus, it is possible that SorCS2 plays a role in the pathophysiology of depression by regulating the BDNF-TrkB system. METHODS: In the present study, SorCS2 expression in different brain regions [hippocampus, medial prefrontal cortex (mPFC), hypothalamus, amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc)] was thoroughly investigated in the chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression. The changes in depressive-like behaviors, the hippocampal BDNF signaling cascade, and amounts of hippocampal immature neurons were further investigated after SorCS2 overexpression by microinjection of the adenovirus associated virus vector containing the coding sequence of mouse SorCS2 (AAV-SorCS2) into the hippocampus of mice exposed to CSDS or CUMS. RESULTS: It was found that both CSDS and CUMS significantly decreased the protein and mRNA expression of SorCS2 in the hippocampus but not in other brain regions. Chronic stress also notably downregulated the level of hippocampal SorCS2-TrkB binding in mice. In contrast, AAV-based genetic overexpression of hippocampal SorCS2 fully reversed the chronic stress-induced not only depressive-like behaviors but also decreased SorCS2-TrkB binding, BDNF signaling pathway, and amounts of immature neurons in the hippocampus of mice. CONCLUSION: All these results suggest that enhancing the hippocampal SorCS2 expression protects against chronic stress, producing antidepressant-like actions. Hippocampal SorCS2 may participate in depression neurobiology and be a potential antidepressant target. SIGNIFICANCE STATEMENT: Targeting of proteins to distinct subcellular compartments is essential for neuronal activity and modulated by VPS10P domain receptors which include SorCS2. In mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Our study is the first direct evidence preliminarily showing that SorCS2 plays a role in depression neurobiology. It was found that chronic stress induced not only depressive-like behaviors but also decreased SorCS2 expression in the hippocampus. Chronic stress did not affect SorCS2 expression in the mPFC, hypothalamus, amygdala, VTA, or NAc. In contrast, genetic overexpression of hippocampal SorCS2 prevented against chronic stress, producing antidepressant-like actions in mice. Thus, hippocampal SorCS2 is a potential participant underlying depression neurobiology and may be a novel antidepressant target. Our study may also extend the knowledge of the neurotrophic hypothesis of depression.

Risk prediction model of uterine corpus endometrial carcinoma based on immune-related genes.

BACKGROUND: Given the significant role of immune-related genes in uterine corpus endometrial carcinoma (UCEC) and the long-term outcomes of patients, our objective was to develop a prognostic risk prediction model using immune-related genes to improve the accuracy of UCEC prognosis prediction. METHODS: The Limma, ESTIMATE, and CIBERSORT methods were used for cluster analysis, immune score calculation, and estimation of immune cell proportions. Univariate and multivariate analyses were utilized to develop a prognostic risk model for UCEC. Risk model scores and nomograms were used to evaluate the models. String constructs a protein-protein interaction (PPI) network of genes. The qRT-PCR, immunofluorescence, and immunohistochemistry (IHC) all confirmed the genes. RESULTS: Cluster analysis divided the immune-related genes into four subtypes. 33 immune-related genes were used to independently predict the prognosis of UCEC and construct the prognosis model and risk score. The analysis of the survival nomogram indicated that the model has excellent predictive ability and strong reliability for predicting the survival of patients with UCEC. The protein-protein interaction network analysis of key genes indicates that four genes play a pivotal role in interactions: GZMK, IL7, GIMAP, and UBD. The quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and immunohistochemistry (IHC) all confirmed the expression of the aforementioned genes and their correlation with immune cell levels. This further revealed that GZMK, IL7, GIMAP, and UBD could potentially serve as biomarkers associated with immune levels in endometrial cancer. CONCLUSION: The study identified genes related to immune response in UCEC, including GZMK, IL7, GIMAP, and UBD, which may serve as new biomarkers and therapeutic targets for evaluating immune levels in the future.