Expression patterns of mechanosensitive ion channel PIEZOs in irreversible pulpitis.

BACKGROUND: Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. MATERIALS AND METHODS: Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman's correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test. RESULTS: Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1. CONCLUSIONS: This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.

Nocardia farcinica brain abscess with torque teno virus co-infection: A case report.

Background: Brain abscesses caused by Nocardia are rare and difficult to diagnose. Nocardia farcinica is among the most common species; however, the conventional diagnosis of N. farcinica infection consists of cerebrospinal fluid (CSF) and blood culture and Gram staining. These procedures prolong the time to diagnosis and initiating treatment. Case presentation: A 69-year-old woman with diabetes mellitus presented with headaches and dizziness persisting for 2 weeks, which was initially diagnosed as a brain abscess. Due to the unusual presentation and rapid progression of symptoms, she underwent surgical resection of the brain abscess. No pathogens were detected in blood or CSF cultures. However, metagenomic next-generation sequencing (mNGS) identified N. farcinica and Torque teno virus in pus extracted from the abscesses. The patient received appropriate antibiotic therapy and recovered fully without any residual neurological deficits. Conclusion: mNGS useful for prompt diagnosis and selection of antibiotic therapy for brain abscesses caused by Nocardia. Surgical intervention is necessary in some cases.

Cost-effectiveness of screening for amblyopia among kindergarten children in China.

Objective: Current cost-effectiveness analyses of amblyopia screening are mainly from western countries. It remains unclear whether it is cost-effective to implement a preschool amblyopia screening programme in China. Our study aimed to evaluate the cost-effectiveness of a hypothetical kindergarten-based amblyopia screening versus non-screening among 3-year-old children. Methods: We developed a decision tree combined with a Markov model to compare the cost and effectiveness of screening versus non-screening for 3-year-old children from a third-party payment perspective. The primary outcomes were quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Costs were obtained from expert opinions in different regions of China. Transition probabilities and health utilities were mainly based on published literature and open sources. Sensitivity analyses were performed to assess the impact of parameters' uncertainty on results. Results: Base-case analysis demonstrated that the ICER of screening versus non-screening was $17,466/QALY, well below the WTP threshold ($38,223/QALY) for China. One-way sensitivity analysis showed that the prevalence of amblyopia, the transition probability per year from untreated amblyopia to healthy, and the discount rate were the top three factors. The likelihood of cost-effectiveness of screening compared with non-screening was 92.56%, according to probabilistic sensitivity analysis. Scenario analysis also indicated that ICER was lower than the WTP threshold even if the time horizon was shortened or the screening was delayed to the age of 4 or 5. Conclusions: Amblyopia screening could be considered a cost-effective strategy compared to non-screening for 3-year-old children in China. Screening for children at the age of 4 or 5 may even yield better results.

Role of αENaC in root resorption of adjacent teeth due to entirely impacted mandibular third molars.

BACKGROUND: Entirely impacted mandibular third molar (EIM3M) concerns the pathological external root resorption (ERR) of the adjacent mandibular second molar (M2M) and formation of granulation tissue between two molars. The study aimed to clarify the effect of αENaC, a mechano-sensitive molecule, to explore the mechanical mechanism in this scenario. METHODS: The force EIM3M exerted on M2M was proved by finite element analysis. αENaC expressions were tested by real-time polymerase chain reaction (PCR), immunoblotting and immunofluorescence. Inflammatory and epithelial-mesenchymal transition (EMT)-related molecules expressions were also detected by real-time PCR. The correlation was analyzed by Spearman's correlation analysis, and receiver-operator characteristic (ROC) curve was further exhibited. RESULTS: The force was concentrated in the ERR area. αENaC was upregulated, positively correlated with ERR degree and localized to the fibroblasts in ERR granulation tissues. Moreover, αENaC was respectively and positively associated with elevated TNF-α and N-cadherin in ERR granulation tissues. More importantly, ROC analysis verified αENaC as a novel indication of the incidence of this disease. CONCLUSIONS: Our finding revealed the force from EIM3M causing ERR of M2M, and elucidated the expression and localization of αENaC and its positive correlation with inflammation, EMT and disease severity, suggesting a novel indication in this disease.

A novel automated multi-cycle magnetic solid-phase extraction coupled to LC-MS/MS to study the disorders of six functional B vitamins in patients with gastroenterology and hyperhomocysteinemia.

B vitamins are essential for human life and their disorders can cause a variety of diseases. Solid-phase extraction (SPE) coupled to LC-MS/MS is a preferred technique for determining multiple B vitamins, however, their complexity in real biological matrices makes it hard to achieve satisfactory recovery and accuracy when simultaneous detection. In this study, a novel automated multi-cycle magnetic SPE (MSPE) coupled to the LC-MS/MS method was established using a mixed-mode anion exchange magnetic adsorbent for the simultaneous extraction of six functional B vitamins, including methylmalonic acid, riboflavin, pantothenic acid, 4-pyridoxic acid, folic acid, and 5-methyltetrahydrofolate. After three consecutive MSPE cycles, the recoveries of all analytes were between 51.5% and 89.6%. The method exhibited excellent sensitivity and linearity, with a dynamic range of 200-fold (R > 0.99 for all analytes), exceptional accuracy (ranging between 95.4% and 105.6%) and precision (with RSDs ≤ 6.2%) without significant matrix effects or interferences. Compared to manual SPE method, the automated multi-cycle MSPE method has better feasibility and greater vitamin coverage. It shows a high correlation with the manual method for the detection of 5-methyltetrahydrofolate and folate (R > 0.99). A study of patients from the gastroenterology department showed that those undergoing surgery and those with malignancies may be at risk of folate deficiency. In addition, patients with hyperhomocystinemia had higher levels of methylmalonic acid and lower levels of 5-methyltetrahydrofolate, which correlated with homocysteine levels (R = 0.404 and -0.311, respectively) and showed dose-response relationships. This method is highly automated and cost-effective, with minimal systematic error, making it suitable for the analysis of clinical samples.

Fosaprepitant for postoperative nausea and vomiting in patients undergoing laparoscopic gastrointestinal surgery: a randomised trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear. METHODS: In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours. RESULTS: The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group. CONCLUSIONS: Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension. CLINICAL TRIAL REGISTRATION: NCT04853147.

Ratiometric near-infrared upconversion fluorescence sensor for selectively detecting and imaging of Al3.

Near-infrared (NIR) fluorescent probes provide extremely sensitive Al3+ detection for human health purposes. This research develops novel Al3+ response molecules (HCMPA) and NIR upconversion fluorescent nanocarriers (UCNPs), which respond to Al3+ through ratio NIR fluorescence. UCNPs improve photobleaching and visible light lack in specific HCMPA probes. Additionally, UCNPs are capable of ratio response, which will further enhance signal accuracy. The NIR ratiometric fluorescence sensing system has been successfully used to detect Al3+ within the range 0.1-1000 nM with an accuracy limit of 0.06 nM. Alternatively, a NIR ratiometric fluorescence sensing system integrated with a specific molecule can image Al3+ within cells. This study demonstrates that a NIR fluorescent probe is an effective and highly stable method of measuring Al3+ in cells.

Stepping Up the Kinetics of Li-O2 Batteries by Shrinking Down the Li2O2 Granules through Concertedly Enhanced Catalytic Activity and Photoactivity of Se-Doped LaCoO3.

Owing to their structural tunability for furnishing high catalytic activity and photoactivity, perovskite oxides are a class of promising materials for high-performance photocathode catalysts in a photoassisted lithium oxygen battery (LOB), which is still in its infancy. Herein, single-crystalline LaCoO3 (LCO) is successfully synthesized through a microwave-assisted approach and selenylated to simultaneously introduce anionic doping and oxygen vacancies, boosting not only the electrocatalytic activity toward reversible Li2O2 formation/decomposition, but also the photoactivity to further reduce the charge/discharge polarization. As a result, LOBs utilizing Se-doped LCO as the photocathode catalyst demonstrate a superior performance under illumination in all aspects of energy efficiency, specific capacity, and cycling stability, ranking among the best reported in the literature for perovskite oxides. The photoenhanced charge kinetics is found to be correlated with the accelerated Li2O2 nucleation with lowered granule size, which is key to both the improved charge/discharge capacity and reversibility. The results underscore the tailoring of perovskite structure to aggrandize both the catalytic activity and photoactivity for concertedly promoting the kinetics of LOBs.

Using machine learning for mortality prediction and risk stratification in atezolizumab-treated cancer patients: Integrative analysis of eight clinical trials.

BACKGROUND: Few models exist to predict mortality in cancer patients receiving immunotherapy. Our aim was to build a machine learning-based risk stratification model for predicting mortality in atezolizumab-treated cancer patients. METHODS: Data from 2538 patients in eight atezolizumab-treated cancer clinical trials across three cancer types (non-small-cell lung cancer, bladder transitional cell carcinoma, and renal cell carcinoma) were included. The whole cohort was randomly split into development and validation cohorts in a 7:3 ratio. Machine-learning algorithms (extreme gradient boosting, random forest, logistic regression with lasso regularization, support vector machine, and K-nearest neighbor) were applied to develop prediction models. Model performance was mainly assessed by area under the receiver operating characteristic curve (AUC) value, calibration plot, and decision curve analysis. The probability of death risk was then stratified. RESULTS: One thousand and three hundred and seventy-nine (54.33%) patients died. The random forest (RF) model was overall the best in terms of predictive performance, with the AUC of 0.844 (95% confidence interval [CI]: 0.826-0.862) in the development cohort and 0.786 (95% CI: 0.754-0.818) in the validation cohort for predicting mortality. Twelve baseline variables contributing to mortality prediction in the RF model were C-reactive protein, PD-L1 level, cancer type, prior liver metastasis, derived neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, hemoglobin, white blood cell count, number of metastatic sites, pulse rate, and Eastern Cooperative Oncology Group (ECOG) performance status. A total of 1782 (70.2%) patients were separated into the high-risk and 756 (29.8%) low-risk groups. Patients in the high-risk group were significantly more likely to die, experience disease progression, discontinue study, and discontinue treatment than patients in the low-risk group (all p values < 0.001). Risk groups were not associated with immune-related adverse events and grades 3-5 treatment-related adverse events (all p values > 0.05). CONCLUSION: RF model has good performance in mortality prediction and risk stratification for cancer patients receiving atezolizumab monotherapy.

Profiling of bile acids and activated receptor S1PR2 in gingival tissues of periodontitis patients.

BACKGROUND: Bile acids, as a group of cholesterol metabolites, play important roles in inflammation and bone metabolism. However, the possible link between bile acids and periodontitis is still unclear. This study aimed to clarify the alterations of the bile acid profile and corresponding receptor expression levels in periodontitis patients, and evaluate their association with periodontitis severity. METHODS: The concentrations of 15 bile acids in gingival tissues from 16 periodontitis patients and 16 healthy individuals were tested by metabolomics. Sphingosine-1-phosphate receptor 2 (S1PR2) expression was determined by real-time PCR and immunohistochemistry, which was also validated in two datasets, GSE16134 and GSE10334. The correlation between bile acids, S1PR2, and clinical parameters was analyzed by Spearman's correlation analysis, and receiver-operator characteristic (ROC) curves were examined to access the ability of bile acids and S1PR2 for defining local periodontitis status. RESULTS: In the periodontitis group, concentrations of total bile acids were elevated by increases of all bile acid forms, and five conjugated bile acids were significantly increased. Meanwhile, the expression of their receptor, S1PR2, was also upregulated in the periodontitis group. Positive correlations were further observed between glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), S1PR2, and periodontal clinical parameters. ROC analysis also showed combinations of two bile acids (GCA and TCDCA) with S1PR2 as novel signatures for indicating local periodontitis status. CONCLUSION: Our findings demonstrated the alterations of the bile acid profile and receptor S1PR2 expression in periodontitis patients, and provided evidence of association between bile acids and periodontitis status.

Curdione Relieved Isoproterenol-Induced Myocardial Damage through Inhibiting Oxidative Stress and Apoptosis.

Isoproterenol (ISO) is widely used to treat bronchial asthma, cardiogenic or septic shock, complete atrioventricular block, and cardiac arrest. However, it can also cause myocardial damage owing to infarct-like necrosis. Curdione, an extract of the Chinese herb Rhizoma Curcumae, has a variety of pharmacological activities, including cardioprotective effects. In this study, we investigated the protective effects of curdione and its underlying mechanisms in an ISO-induced myocardial injury model. Our results showed that curdione attenuated ISO-induced H9c2 cell proliferation inhibition and lactic dehydrogenase (LDH) release. Curdione ameliorated morphological damage and reduced the ISO-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB) and LDH. Furthermore, curdione inhibited ISO-induced cell apoptosis, modulated the expression of Bcl-2 and Bax proteins, repealed the accumulation of ISO-induced reactive oxygen species (ROS), prevented mitochondrial dysfunction, and activated the Nrf2/SOD1/HO-1 signaling pathway. The above results show that curdione exerts a protective effect against ISO-induced myocardial damage by inhibiting apoptosis and oxidative stress, suggesting that curdione is a potential therapeutic strategy to prevent ISO-induced myocardial damage.

A Clinical Prediction Model for Patients with Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Stenosis.

BACKGROUND: Acute large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS-LVO) increases the difficulty of revascularization, resulting in frequent re-occlusion. The establishment of its pathogenesis before endovascular treatment (EVT) is beneficial for patients. We aimed at developing and validating a clinical prediction model for ICAS-LVO patients before EVT. METHODS: Patients with acute large vessel occlusion at Jining No. 1 People's Hospital from January 2019 to September 2021 were retrospectively included as the training cohort. The 70 patients who met the inclusion and exclusion criteria were included in the validation cohort (October 2021 to May 2022). Demographics, onset form, medical history, digital subtraction angiography (DSA) imaging data, and laboratory test data were collected. Preprocedural parameters for the ICAS-LVO risk prediction model were established by stepwise logistic regression controlling for the confounding effects. Then, we constructed a nomogram model and evaluated its performance via the Hosmer-Lemeshow goodness-of-fit test, area under the ROC curve (AUC) analysis. RESULTS: The 231 acute LVO patients were included in the final analysis, 74 (32.3%) patients were ICAS-LVO. A preoperative diagnosis prediction model consisting of five predictors for ICAS-LVO, including fluctuating symptoms, NIHSS < 16, atrial fibrillation, tapered sign, and ASITN/SIR score ≥ 2. The model depicted an acceptable calibration (Hosmer-Lemeshow test, p = 0.451) and good discrimination (AUC, 0.941; 95% confidence interval, 0.910-0.971). The optimal cut-off value for the ICAS-LVO scale was 2 points, with 86.5% sensitivity, 91.1% specificity, and 90.5% accuracy. In the validation cohort, the discriminative ability was promising with an AUC value of 0.897, implying a good predictive performance. CONCLUSION: The established ICAS-LVO scale, which is composed of five predictors: fluctuating symptoms, NIHSS < 16, atrial fibrillation, tapered sign, and ASITN/SIR score ≥ 2, has a good predictive value for ICAS-LVO in Chinese populations.

Upregulated Vanins and their potential contribution to periodontitis.

BACKGROUND: Although Vanins are closely related to neutrophil regulation and response to oxidative stress, and play essential roles in inflammatory diseases with clinical significance, their contribution to periodontitis remains to be determined. This research was designed to assess the expression of Vanins in human gingiva, and to define the relationship between Vanins and periodontitis. METHODS: Forty-eight patients with periodontitis and forty-two periodontal healthy individuals were enrolled for gingival tissue sample collection. Expression levels of VNN1, VNN2 and VNN3 were evaluated by RT-qPCR and validated in datasets GSE10334 and GSE16134. Western blot and immunohistochemistry identified specific proteins within gingiva. The histopathological changes in gingival sections were investigated using HE staining. Correlations between Vanins and clinical parameters, PD and CAL; between Vanins and inflammation, IL1B; and between Vanins and MPO in periodontitis were investigated by Spearman's correlation analysis respectively. Associations between VNN2 and indicators of neutrophil adherence and migration were further validated in two datasets. RESULTS: Vanins were at higher concentrations in diseased gingival tissues in both RT-qPCR and dataset analysis (p < 0.01). Assessment using western blot and immunohistochemistry presented significant upregulations of VNN1 and VNN2 in periodontitis (p < 0.05). The higher expression levels of Vanins, the larger the observed periodontal parameters PD and CAL (p < 0.05), and IL1B (p < 0.001). Moreover, positive correlations existed between VNN2 and MPO, and between VNN2 and neutrophil-related indicators. CONCLUSION: Our study demonstrated upregulation of Vanins in periodontitis and the potential contribution of VNN2 to periodontitis through neutrophils-related pathological processes.

Machine learning models including insulin resistance indexes for predicting liver stiffness in United States population: Data from NHANES.

Background: Prevention and treatment of liver fibrosis at an early stage is of great prognostic importance, whereas changes in liver stiffness are often overlooked in patients before the onset of obvious clinical symptoms. Recognition of liver fibrosis at an early stage is therefore essential. Objective: An XGBoost machine learning model was constructed to predict participants' liver stiffness measures (LSM) from general characteristic information, blood test metrics and insulin resistance-related indexes, and to compare the fit efficacy of different datasets for LSM. Methods: All data were obtained from the National Health and Nutrition Examination Survey (NHANES) for the time interval January 2017 to March 2020. Participants' general characteristics, Liver Ultrasound Transient Elastography (LUTE) information, indicators of blood tests and insulin resistance-related indexes were collected, including homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic score for insulin resistance (METS-IR). Three datasets were generated based on the above information, respectively named dataset A (without the insulin resistance-related indexes as predictor variables), dataset B (with METS-IR as a predictor variable) and dataset C (with HOMA-IR as a predictor variable). XGBoost regression was used in the three datasets to construct machine learning models to predict LSM in participants. A random split was used to divide all participants included in the study into training and validation cohorts in a 3:1 ratio, and models were developed in the training cohort and validated with the validation cohort. Results: A total of 3,564 participants were included in this study, 2,376 in the training cohort and 1,188 in the validation cohort, and all information was not statistically significantly different between the two cohorts (p > 0.05). In the training cohort, datasets A and B both had better predictive efficacy than dataset C for participants' LSM, with dataset B having the best fitting efficacy [±1.96 standard error (SD), (-1.49,1.48) kPa], which was similarly validated in the validation cohort [±1.96 SD, (-1.56,1.56) kPa]. Conclusions: XGBoost machine learning models built from general characteristic information and clinically accessible blood test indicators are practicable for predicting LSM in participants, and a dataset that included METS-IR as a predictor variable would improve the accuracy and stability of the models.

Novel Hybrids of 3-Substituted Coumarin and Phenylsulfonylfuroxan as Potent Antitumor Agents with Collateral Sensitivity against MCF-7/ADR.

Twenty-three new coumarin-furoxan hybrids were synthesized, which exhibited nanomole antiproliferation activities in A2780, A2780/CDDP, MCF-7/ADR, and MDA-MB-231. Among them, compound 9 showed the strongest collateral sensitivity to MCF-7/ADR with 499-fold potency compared with MCF-7. Notably, the solubility of compound 9 increased 70-fold compared with the lead 2. And preliminary pharmacological studies displayed that compound 9 obviously increased Rh123 accumulation in MCF-7/ADR and released NO to produce ROS in lysosomes, which were able to damage lysosomal membrane and induce apoptosis. These results reasonably explained that the collateral sensitivity of compound 9 to MCF-7/ADR was closely related to P-gp-mediated lysosome damage and apoptosis. Additionally, compound 9 showed a very weak cytotoxicity both in MCF-10A and hERG potassium channels and had a desirable safety in ion cyclotron resonance (ICR) mice. Hence, compound 9 was merited to further study for developing a desirable candidate against MDR MCF-7/ADR via a potential mechanism of collateral sensitivity in MDR cancer cell lines.

Homogenizing Li2CO3 Nucleation and Growth through High-Density Single-Atomic Ru Loading toward Reversible Li-CO2 Reaction.

The high activation barrier and sluggish kinetics of Li2CO3 decomposition impose a severe challenge on the development of a Li-CO2 battery with high Coulombic efficiency. To tackle this issue, herein we devise a novel synthetic tactic by combining electrostatic assembly with in situ polycondensation to obtain a single-atomic Ru catalyst of high density up to ∼5 wt %. When deployed to the CO2 cathode, the catalyst delivered an extraordinary capacity of 44.7 Ah g-1, an ultralow charge/discharge polarization of 0.97 V at 0.1 A g-1 (1.90 V at 2 A g-1), and a long-term cycling stability up to 367 cycles at 1 Ah g-1 (196 cycles at 2 Ah g-1), outshining most of the state-of-the-art CO2 cathode catalysts reported today. Further through extensive in situ and ex situ electroanalytical, spectroscopic, and microscopic characterizations, we attribute the superb battery performance mainly to the highly reversible Li2CO3 formation/decomposition, facilitated by the homogenized and downsized Li2CO3 nucleation and growth on account of the high density single-atomic Ru loading. This work not only offers a facile method to fabricate single-atom catalysts with high mass loading but also sheds light on promoting the reversible Li-CO2 reaction by mediating product morphology.

Impairment of response inhibition to emotional face stimuli in individuals with subclinical depression.

Response inhibition, a crucial component of executive function, is closely related to personal impulse control, social adaption, and mental health. Previous studies have found response inhibition deficit in patients with major depressive disorder, but whether it also exists in individuals with subclinical depression (SD) remains unclear. This study aimed to identify the ability of response inhibition to emotional face stimuli both under explicit and implicit conditions in individuals with SD. Thirty-six subclinical depressed college students and 39 healthy individuals were recruited and administered the non-emotional, explicit, and implicit emotional stop-signal tasks (SSTs). Mixed-model analyses of variance were used to analyze the differences between and within groups. In implicit emotional SST, the results showed a significant longer stop-signal response time, a shorter stop-signal delay time, a shorter go reaction time, and a similar proportion of stop success in the SD group compared to healthy controls. However, the above indices showed no significant difference between the two groups in the non-emotional SST and explicit emotional SST. These findings suggest a possible defect of response inhibition in implicit emotional processing in individuals with SD, which may potentially serve as a marker of susceptibility to depression and thus be applied to early screening and intervention for major depressive disorder.

Protective effects of interleukin-22 on oxalate-induced crystalline renal injury via alleviating mitochondrial damage and inflammatory response.

Oxalate-induced crystalline kidney injury is one of the most common types of crystalline nephropathy. Unfortunately, there is no effective treatment to reduce the deposition of calcium oxalate crystals and alleviate kidney damage. Thus, proactive therapeutic is urgently needed to alleviate the suffering it causes to patient. Here, we investigated whether IL-22 exerted nephroprotective effects to sodium oxalate-mediated kidney damage and its potential mechanism. Crystalline kidney injury models were developed in vitro and in vivo that was often observed in clinic. We provided evidence that IL-22 could effectively decrease the accumulation of ROS and mitochondrial damage in cell and animal models and reduce the death of TECs. Moreover, IL-22 decreased the expression of the NLRP3 inflammasome and mature IL-1ß in renal tissue induced by sodium oxalate. Further studies confirmed that IL-22 could play an anti-inflammatory role by reducing the levels of cytokines such as IL-1ß, IL-18, and TNF-α in serum. In conclusion, our study confirmed that IL-22 has protective effects on sodium oxalate-induced crystalline kidney injury by reducing the production of ROS, protecting mitochondrial membrane potential, and inhibiting the inflammatory response. Therefore, IL-22 may play a potential preventive role in sodium oxalate-induced acute renal injury. KEY POINTS: • IL-22 could reduce sodium oxalate-mediated cytotoxicity and ameliorate renal injury. • IL-22 could alleviate oxidative stress and mitochondrial dysfunction induced by sodium oxalate. • IL-22 could inhibit inflammatory response of renal injury caused by sodium oxalate.

A "Blockchain" Synergy in Conductive Polymer-Filled Metal-Organic Frameworks for Dendrite-Free Li Plating/Stripping with High Coulombic Efficiency.

The performance of lithium-metal batteries is severely hampered by uncontrollable dendrite growth and volume expansion on the metal anodes. Inspired by the "blockchain" concept in data mining, here we utilize a conductive polymer-filled metal-organic framework (MOF) as the lithium host, in which polypyrrole (PPy) serves as the "chain" to interlink Li "blocks" stored in the MOF pores. While the N-rich PPy guides fast Li+ infiltration/extrusion and serves as the nucleation sites for isotropic Li growth, the MOF pores compartmentalize bulk Li deposition for 3D matrix Li storage, leading to low-barrier and dendrite-free Li plating/stripping with superb Coulombic efficiency. The as-fabricated lithium-metal anodes operate over 700 cycles at 5 mA cm-2 in symmetric cells, and 800 cycles at 1 C in full cells with a per-cycle capacity loss of only 0.017 %. This work might open a new chapter for Li-metal anode construction by introducing the concept of "blockchain" management of Li plating/stripping.

GPR120 induces regulatory dendritic cells by inhibiting HK2-dependent glycolysis to alleviate fulminant hepatic failure.

Fulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. Using Propionibacterium acnes (P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn't directly target T cells, but dramatically induced a distinct population of CD11c+MHC IIlowCD80lowCD86low regulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.