NUMB dysfunction defines a novel mechanism underlying hyperuricemia and gout.

Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

GeneCompass: deciphering universal gene regulatory mechanisms with a knowledge-informed cross-species foundation model.

Deciphering universal gene regulatory mechanisms in diverse organisms holds great potential for advancing our knowledge of fundamental life processes and facilitating clinical applications. However, the traditional research paradigm primarily focuses on individual model organisms and does not integrate various cell types across species. Recent breakthroughs in single-cell sequencing and deep learning techniques present an unprecedented opportunity to address this challenge. In this study, we built an extensive dataset of over 120 million human and mouse single-cell transcriptomes. After data preprocessing, we obtained 101,768,420 single-cell transcriptomes and developed a knowledge-informed cross-species foundation model, named GeneCompass. During pre-training, GeneCompass effectively integrated four types of prior biological knowledge to enhance our understanding of gene regulatory mechanisms in a self-supervised manner. By fine-tuning for multiple downstream tasks, GeneCompass outperformed state-of-the-art models in diverse applications for a single species and unlocked new realms of cross-species biological investigations. We also employed GeneCompass to search for key factors associated with cell fate transition and showed that the predicted candidate genes could successfully induce the differentiation of human embryonic stem cells into the gonadal fate. Overall, GeneCompass demonstrates the advantages of using artificial intelligence technology to decipher universal gene regulatory mechanisms and shows tremendous potential for accelerating the discovery of critical cell fate regulators and candidate drug targets.

Serum ionized magnesium acts as an independent protective factor against bone erosion in patients with gouty arthritis: a cross-sectional study.

Background: Gouty arthritis is a common inflammatory arthritis. The recurrent gout attacks severely damage the joint's function, lead to bone erosion, and affect bone metabolism. The role of magnesium (Mg) ions in bone homeostasis has been recognized, whereas its specific relationship with gouty bone erosion remains unclear. This study examined the association between serum ionized Mg levels and bone erosion in patients with gout arthritis. Methods: A total of 769 patients with gout arthritis were included in the study. Participants were classified into four groups based on the quartiles of the serum ionized Mg level. Logistic regression analysis assessed the association between serum ionized Mg and bone erosion. Results: Compared to patients without bone erosion, serum ionized Mg levels were lower in gout patients with bone erosion (p<0.001). When dividing serum ionized Mg into quartiles, the prevalence rate of bone erosion in group Q1, representing the patients with the lowest serum ionized Mg levels, was notably higher than in Q2, Q3, and Q4 (60.2% vs. 43.6%, 45.6%, 40.3%, p<0.001). Multiple logistic regression analysis revealed that patients in Q2-Q4 had a lower odds ratio (OR) of bone erosion compared to those in Q1 (ORs were 0.520, 0.533, and 0.411 in Q2-Q4, respectively, p<0.001). Conclusion: The incidence of bone erosion is higher in gout arthritis patients with lower serum ionized Mg levels. High serum ionized Mg levels may be an independent protective factor for bone erosion in gout arthritis. Thus, Mg supplementation may be a promising approach to prevent or slow down the development of bone erosion in gouty arthritis.

Luteinizing hormone is independently associated with high-sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross-sectional study.

BACKGROUND: It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. METHODS: This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. RESULTS: Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (ß = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. CONCLUSIONS: Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

Tripartite interaction representation algorithm for crystal graph neural networks.

Driven by emerging research paradigms, the application of artificial intelligence models presents innovative tools for designing materials and optimizing their performance. In the field of materials science, there is a current research emphasis on exploring techniques for characterizing material structures to achieve precise descriptions. This paper proposes a crystal graph convolution neural network model that incorporates a tripartite interaction approach. The model not only incorporates atomic information, bond lengths, and bond angles but also offers a method for updating atoms and bond lengths, facilitating accurate descriptions of crystal structures by capturing implicit structural information. Focusing on predicting the formation energy of crystalline compounds, our results demonstrate improved predictive accuracy compared to existing representation algorithms. The average error of the formation energy in the random dataset, demonstrating robust generalization, is merely 0.048eV/atom, with an impressive R 2 value of 0.994. Additionally, this paper establishes a crystal graph neural network framework for predicting algorithm performance. By integrating automatic parallel algorithms and an automated process, we achieve a synthesis of these techniques, enhancing computational efficiency and streamlining algorithm usage.

GraspDiff: Grasping Generation for Hand-Object Interaction With Multimodal Guided Diffusion.

Grasping generation holds significant importance in both robotics and AI-generated content. While pure network paradigms based on VAEs or GANs ensure diversity in outcomes, they often fall short of achieving plausibility. Additionally, although those two-step paradigms that first predict contact and then optimize distance yield plausible results, they are always known to be time-consuming. This paper introduces a novel paradigm powered by DDPM, accommodating diverse modalities with varying interaction granularities as its generating conditions, including 3D object, contact affordance, and image content. Our key idea is that the iterative steps inherent to diffusion models can supplant the iterative optimization routines in existing optimization methods, thereby endowing the generated results from our method with both diversity and plausibility. Using the same training data, our paradigm achieves superior generation performance and competitive generation speed compared to optimization-based paradigms. Extensive experiments on both in-domain and out-of-domain objects demonstrate that our method receives significant improvement over the SOTA method. We will release the code for research purposes.

Adolescent Takayasu's arteritis with hypertensive intracerebral hemorrhage: a case report and literature review.

Takayasu's arteritis is a primary systemic vasculitis that affects predominantly large vessels, affecting the aorta and its major branches. We report a case of adolescent female patient who initially experienced numbness and weakness in her limbs, subsequently developing severe hypertension. Physical examination revealed uneven blood pressure in the limbs and a murmur in the auscultation area of the abdominal aorta without decreased pulses. Auxiliary examinations revealed diffuse blood vessel stenosis, leading to the diagnosis of Takayasu's arteritis. One month later, the patient was diagnosed with multiple cerebral hemorrhages following sudden impairment of limb movement. Digital subtraction angiography did not reveal any evident vascular malformations or aneurysms. Following surgery and biologic intervention with tocilizumab, the patient's condition improved, with no new bleeding episodes and stable blood pressure control achieved. We also reviewed the literature that have been previously reported with hypertensive intracerebral hemorrhage complicated by Takayasu's arteritis. We recommend that Takayasu's arteritis be taken into account when considering the hypertension in young patients. Timely vascular imaging and standardized treatment are imperative for diagnosing and managing effectively.

Pathogenic Bacteria and Antimicrobial Resistance in Hospital-Acquired Urinary Tract Infections among Patients with Diabetic Nephropathy.

OBJECTIVE: Hospital-acquired urinary tract infections (UTIs) are common complications in patients with diabetic nephropathy (DN), leading to increased mortality and increased medical resource utilisation. This study investigated hospital-acquired UTIs in patients with DN, focusing on prevalent pathogens and drug resistance to inform clinical management. METHODOLOGY: This retrospective study analysed 141 patients with hospital-acquired UTIs admitted to The Affiliated Hospital of Qingdao University from January 1, 2013 to December 31, 2022, using the Yidu Cloud database. Among them, 109 had DN, and 32 had nondiabetic nephropathy (NDN). Patient demographics, pathogen distribution, and antibiotic resistance were statistically evaluated. RESULTS: The incidence of hospital-acquired UTIs was significantly higher in patients with DN compared to those with NDN (p < 0.0001), with a higher prevalence in women (p = 0.004). Gram-negative bacteria, particularly Escherichia coli (E. coli) and Klebsiella pneumoniae, were the primary pathogens in patients with DN and NDN. E. coli infections were more common in the DN group (p = 0.017). These pathogens exhibited high susceptibility to carbapenems, ß-lactamase inhibitors, amikacin, nitrofurantoin, and minocycline; However, they showed significant resistance to quinolones, cephalosporin, and penicillins. CONCLUSIONS: Preventing hospital-acquired UTIs in patients with DN is crucial. Effective treatment requires selecting antibacterial drugs based on pathogen resistance profiles.

Clinicopathological features affecting the efficacy in 131I ablation therapy of papillary thyroid carcinoma with lymph node metastasis.

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131I ablation therapy. Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed. Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group. Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR.

Primary exophytic urothelial carcinoma of the bladder: A case report.

RATIONALE: Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients. PATIENT CONCERNS: An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss. DIAGNOSIS: Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC. INTERVENTIONS: The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy. OUTCOMES: The patient's mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery. LESSONS: UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.

Prevalence and Risk Factors of Chronic Kidney Disease in Patients With Type 2 Diabetes in China: Cross-Sectional Study.

BACKGROUND: Chronic kidney disease (CKD) is a significant long-term complication of diabetes and is a primary contributor to end-stage kidney disease. OBJECTIVE: This study aimed to report comprehensive nationwide data on the prevalence, screening, and awareness rates of CKD in Chinese patients with type 2 diabetes, along with associated risk factors. METHODS: Baseline data analysis of the ongoing prospective, observational IMPROVE study was conducted. The study cohort comprised patients who had been diagnosed with type 2 diabetes more than 12 months prior, received at least 1 hypoglycemic medication, and were aged ≥18 years. The participants completed questionnaires and underwent laboratory assessments, including blood and urine samples. The data encompassed patient demographics, medical history, concurrent medications, and comorbidities. Comprehensive evaluations involved physical examinations, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, fasting blood lipid profile, and urinalysis. Descriptive statistics were applied for data interpretation, and logistic regression analyses were used to identify the CKD-associated risk factors in patients with type 2 diabetes. RESULTS: A national study from December 2021 to September 2022 enlisted 9672 participants with type 2 diabetes from 45 hospitals that had endocrinology departments. The enrollees were from diverse regions in China, as follows: central (n=1221), east (n=3269), south (n=1474), north (n=2219), and west (n=1489). The prevalence, screening, and awareness rates of CKD among patients with type 2 diabetes were 31% (2997/9672), 27% (810/2997), and 54.8% (5295/9672), respectively. Multivariate binary regression analysis revealed that the CKD risk factors were screening, awareness, smoking, age, diabetes duration, concurrent antihypertensive and microcirculation medications, diabetic complications (foot, retinopathy, and neuropathy), hypertension, elevated low-density lipoprotein (LDL) cholesterol, and suboptimal glycemic control. Subgroup analysis highlighted an increased CKD prevalence among older individuals, those with prolonged diabetes durations, and residents of fourth-tier cities. Residents of urban areas that had robust educational and economic development exhibited relatively high awareness and screening rates. Notably, 24.2% (1717/7107) of patients with an eGFR ≥90 mL/min/1.73 m2 had proteinuria, whereas 3.4% (234/6909) who had a UACR <30 mg/g presented with an eGFR <60 mL/min/1.73 m2. Compared with patients who were cognizant of CKD, those who were unaware of CKD had increased rates of HbA1c ≥7%, total cholesterol >5.18 µmol/L, LDL cholesterol >3.37 µmol/L, BMI ≥30 kg/m2, and hypertension. CONCLUSIONS: In a Chinese population of adults with type 2 diabetes, the CKD prevalence was notable, at 31%, coupled with low screening and awareness rates. Multiple risk factors for CKD have been identified. TRIAL REGISTRATION: ClinicalTrials.gov NCT05047471; https://clinicaltrials.gov/study/NCT05047471.

Addressing the Accuracy-Cost Trade-off in Material Property Prediction Using a Teacher-Student Strategy.

Deep learning has catalyzed a transformative shift in material discovery, offering a key advantage over traditional experimental and theoretical methods by significantly reducing associated costs. Models adept at predicting properties from chemical compositions alone do not require structural information. However, this cost-efficient approach compromises model precision, particularly in Chemical Composition-based Property Prediction Models (CPMs), which are notably less accurate than Structure-based Property Prediction Models (SPMs). Addressing this challenge, our study introduces a novel Teacher-Student (TS) strategy, where a pretrained SPM serves as an instructive 'teacher' to enhance the CPM's precision. This TS strategy successfully harmonizes low-cost exploration with high accuracy, achieving a significant 47.1% reduction in relative error in scenarios involving 100 data entries. We also evaluate the effectiveness of the proposed strategy by employing perovskites as a case study. This method represents a significant advancement in the exploration and identification of valuable materials, leveraging CPM's potential while overcoming its precision limitations.

Efficacy and safety of omega-3-acid ethyl acetate 90 capsules in severe hypertriglyceridemia: A randomized, controlled, multicenter study.

Omega-3-acid ethyl acetate 90 capsules (containing 465 mg of eicosapentaenoic acid and 375 mg docosahexaenoic acid) is composed of highly purified omega-3 polyunsaturated fatty acid (PUFA) ethyl esters, whose lipid-lowering effect for severe hypertriglyceridemia (HTG) treatment is unclear. This study aimed to evaluate the efficacy and safety of omega-3-acid ethyl acetate 90 capsules in patients with severe HTG. In this randomized, double-blind, placebo-controlled, multicenter study, 239 patients with severe HTG were enrolled and randomized (1:1) into omega-3 group (N = 122) and placebo group (N = 117) to receive 12-week corresponding treatments. Lipid-related indexes were obtained at treatment initiation (W0), 4 weeks (W4), W8, and W12 after treatment. Adverse events and adverse drug reactions were recorded. Triacylglycerols (TAG), total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein C-III (Apo C-III) at W4, W8, and W12 were decreased in the omega-3 group versus the placebo group (all p < 0.05). Moreover, the percentage changes of TAG, TC, non-HDL-C, and VLDL-C from W0 to W4, W8, and W12, and the percentage change of Apo C-III from W0 to W4 and W8, were more obvious in the omega-3 group compared with the placebo group (all p < 0.05). However, no difference was observed in the percentage changes of HDL-C, low-density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C ratio during follow-up between groups (all p > 0.05). Additionally, there was no discrepancy in adverse events and adverse drug reactions between groups (all p > 0.05). Omega-3-acid ethyl acetate 90 capsules exhibit satisfied lipid-lowering effect with tolerable safety profile in patients with severe HTG.

Association between Serum Phosphorus Levels and Diabetic Retinopathy: A Cross-Sectional Study.

Background and Aims: The aim of this study was to investigate the association between serum phosphate levels and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods and Results: The study sample consisted of 1657 T2DM patients hospitalized between 2017 and 2019. Patients were categorized into quartiles based on their serum phosphate levels (Q1-Q4). An increasing trend in the prevalence of DR was observed across these quartiles. Subsequently, logistic regression analysis was employed to adjust for potential confounders, such as gender, age, BMI, and duration of diabetes, and to evaluate the odds ratios (ORs) associated with these quartiles. The prevalence of DR showed an increasing trend with elevated serum phosphate levels. Logistic regression further confirmed that serum phosphate levels remain an independent risk factor for DR. Conclusion: Elevated serum phosphate levels are closely associated with the prevalence of DR in hospitalized T2DM patients. Further studies are needed to establish causality. This trial is registered with chiCTR2000032374.

Association between low-density lipoprotein cholesterol levels and serum uric acid to serum creatinine ratio in Chinese male gout patients.

This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18-83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24-28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (ß = 0.67, 95% CI 0.35-0.98, P < 0.001). Moreover, LDL-C showed a significant positive correlation with SUA/SCr with a BMI of 28 or greater (ß = 0.30, 95% CI 0.05-0.55, P = 0.019). However, no association was found between LDL-C and SUA/SCr with a BMI of less than 24 (ß = 0.42, 95% CI - 0.03-0.86, P = 0.070). LDL-C levels were associated with SUA/SCr in Chinese male gout patients, but this correlation appeared inconsistent among different BMIs. Our findings suggest that LDL-C levels may be more noteworthy in overweight and/or obese male gout patients.

sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-ß via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-ß (Aß) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aß from the brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aß. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aß in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aß. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aß after binding to Aß. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.

Solar-Driven Biomass Reforming for Hydrogen Generation: Principles, Advances, and Challenges.

Hydrogen (H2) has emerged as a clean and versatile energy carrier to power a carbon-neutral economy for the post-fossil era. Hydrogen generation from low-cost and renewable biomass by virtually inexhaustible solar energy presents an innovative strategy to process organic solid waste, combat the energy crisis, and achieve carbon neutrality. Herein, the progress and breakthroughs in solar-powered H2 production from biomass are reviewed. The basic principles of solar-driven H2 generation from biomass are first introduced for a better understanding of the reaction mechanism. Next, the merits and shortcomings of various semiconductors and cocatalysts are summarized, and the strategies for addressing the related issues are also elaborated. Then, various bio-based feedstocks for solar-driven H2 production are reviewed with an emphasis on the effect of photocatalysts and catalytic systems on performance. Of note, the concurrent generation of value-added chemicals from biomass reforming is emphasized as well. Meanwhile, the emerging photo-thermal coupling strategy that shows a grand prospect for maximally utilizing the entire solar energy spectrum is also discussed. Further, the direct utilization of hydrogen from biomass as a green reductant for producing value-added chemicals via organic reactions is also highlighted. Finally, the challenges and perspectives of photoreforming biomass toward hydrogen are envisioned.

Theoretical study of transition metal-doped ß12 borophene as a new single-atom catalyst for carbon dioxide electroreduction.

The electrocatalytic carbon dioxide reduction reaction (CO2RR) presents a viable and cost-effective approach for the elimination of CO2 by transforming it into valuable products. Nevertheless, this process is impeded by the absence of exceptionally active and stable catalysts. Herein, a new type of electrocatalyst of transition metal (TM)-doped ß12-borophene (TM@ß12-BM) is investigated via density functional theory (DFT) calculations. Through comprehensive screening, two promising single-atom catalysts (SACs), Sc@ß12-BM and Y@ß12-BM, are successfully identified, exhibiting high stability, catalytic activity and selectivity for the CO2RR. The C1 products methane (CH4) and methanol (CH3OH) are synthesized with limiting potentials (UL) of -0.78 V and -0.56 V on Sc@ß12-BM and Y@ß12-BM, respectively. Meanwhile, CO2 is more favourable for reduction into the C2 product ethanol (CH3CH2OH) compared to ethylene (C2H4) via C-C coupling on these two SACs. More importantly, the dynamic barriers of the key C-C coupling step are 0.53 eV and 0.73 eV for the "slow-growth" sampling approach in the explicit water molecule model. Furthermore, Sc@ß12-BM and Y@ß12-BM exhibit higher selectivity for producing C1 compounds (CH4 and CH3OH) than C2 (CH3CH2OH) in the CO2RR. Compared with Sc@ß12-BM, Y@ß12-BM demonstrates superior inhibition of the competitive hydrogen evolution reaction (HER) in the liquid phase. These results not only demonstrate the great potential of SACs for direct reduction of CO2 to C1 and C2, but also help in rationally designing high-performance SACs.

Analysis of Factors Related to the Efficacy of Consciousness-Regaining Therapy for Prolonged Disorder of Consciousness: A Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to the efficacy of consciousness-regaining therapy (CRT) for prolonged disorder of consciousness. METHODS: A retrospective analysis was conducted on the case data of 114 patients with prolonged disorder of consciousness (pDOC) admitted to the Department of Functional Neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022 to explore the relevant factors that affect the efficacy of CRT for pDOC. Next, basic information on the cases, data on pDOC disease assessment, CRT methods, and efficacy evaluation were collected. RESULTS: These 114 patients were grouped, and a comparative analysis was done based on the efficacy at the end of treatment. Of these, 61 cases were allotted to the ineffective group and 53 cases to the effective group. There was a lack of statistical difference (P > 0.05) between the 2 groups based on gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of CRT, and CRT duration (P > 0.05). However, secondary hydrocephalus, CRT methods, JFK Coma Recovery Scale-Revised grading before treatment, and extended Glasgow Outcome Scale score at six months after treatment were found to be statistically different. The results of binary logistic regression analysis showed that the type of therapy (OR = 0.169, 95% CI: 0.057-0.508) affected the efficacy of CRT (P < 0.05). CONCLUSIONS: Personalized awakening therapy using various invasive CRT methods could improve the efficacy of therapy for pDOC compared with noninvasive therapy.

EMC10 modulates hepatic ER stress and steatosis in an isoform-specific manner.

BACKGROUND & AIMS: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis. The therapeutic effect of scEMC10-neutralizing antibody on mouse hepatosteatosis was explored. Associations of MASLD with serum scEMC10 and hepatic mEMC10 were determined in two cohorts of participants with MASLD. RESULTS: scEMC10 promoted, while mEMC10 suppressed, the activation of hepatic PERK-eIF2α-ATF4 signaling. Emc10 gene knockout exacerbated, while hepatic overexpression of mEMC10 ameliorated, hepatic ER stress and steatosis in mice challenged with either a methionine- and choline-deficient diet or tunicamycin, highlighting a direct, suppressive role of mEMC10 in MASLD via modulation of hepatic ER stress. Overexpression of scEMC10 promoted, whereas neutralization of circulating scEMC10 prevented, hepatosteatosis in mice with fatty liver, suggesting a role of scEMC10 in MASLD development. Clinically, serum scEMC10 was increased, while hepatic mEMC10 was decreased, in participants with MASLD. Correlative analysis indicated that serum scEMC10 positively, whereas hepatic mEMC10 negatively, correlated with liver fat content and serum ALT, AST, and GGT. CONCLUSIONS: These findings demonstrate a novel isoform-specific role for EMC10 in the pathogenesis of MASLD and identify the secreted isoform as a tractable therapeutic target for MASLD via antibody-based neutralization. IMPACT AND IMPLICATIONS: We have shown the role of EMC10 in the regulation of energy homeostasis and obesity. In this study, we determine the distinct roles of the two isoforms of EMC10 in the regulation of hepatic endoplasmic reticulum stress and steatosis in mice, and report on the associations of the different EMC10 isoforms with metabolic dysfunction-associated steatotic liver disease in humans. Our findings delineate a novel regulatory axis for hepatosteatosis and identify EMC10 as a modulator of the PERK-eIF2α-ATF4 signaling cascade that may be of broad physiological significance. Moreover, our pre-clinical and clinical studies provide evidence of the therapeutic potential of targeting scEMC10 in MASLD.