TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation.

BACKGROUND AND AIMS: Vascular smooth muscle cell (VSMC) senescence is crucial for the development of atherosclerosis, characterized by metabolic abnormalities. Tumour necrosis factor receptor-associated protein 1 (TRAP1), a metabolic regulator associated with ageing, might be implicated in atherosclerosis. As the role of TRAP1 in atherosclerosis remains elusive, this study aimed to examine the function of TRAP1 in VSMC senescence and atherosclerosis. METHODS: TRAP1 expression was measured in the aortic tissues of patients and mice with atherosclerosis using western blot and RT-qPCR. Senescent VSMC models were established by oncogenic Ras, and cellular senescence was evaluated by measuring senescence-associated ß-galactosidase expression and other senescence markers. Chromatin immunoprecipitation (ChIP) analysis was performed to explore the potential role of TRAP1 in atherosclerosis. RESULTS: VSMC-specific TRAP1 deficiency mitigated VSMC senescence and atherosclerosis via metabolic reprogramming. Mechanistically, TRAP1 significantly increased aerobic glycolysis, leading to elevated lactate production. Accumulated lactate promoted histone H4 lysine 12 lactylation (H4K12la) by down-regulating the unique histone lysine delactylase HDAC3. H4K12la was enriched in the senescence-associated secretory phenotype (SASP) promoter, activating SASP transcription and exacerbating VSMC senescence. In VSMC-specific Trap1 knockout ApoeKO mice (ApoeKOTrap1SMCKO), the plaque area, senescence markers, H4K12la, and SASP were reduced. Additionally, pharmacological inhibition and proteolysis-targeting chimera (PROTAC)-mediated TRAP1 degradation effectively attenuated atherosclerosis in vivo. CONCLUSIONS: This study reveals a novel mechanism by which mitonuclear communication orchestrates gene expression in VSMC senescence and atherosclerosis. TRAP1-mediated metabolic reprogramming increases lactate-dependent H4K12la via HDAC3, promoting SASP expression and offering a new therapeutic direction for VSMC senescence and atherosclerosis.

Regional quality analysis of the hydrological environment with an improved random forest model based on the chimpanzee algorithm.

High-precision evaluations of water environment quality are highly important for improving the accuracy of early warning systems of regional water pollution risk and improving the regional water environment. This paper employs the chimp optimization algorithm (ChOA) to enhance the traditional random forest model, resulting in the chimp optimization algorithm-random forest (ChOA-RF) water quality assessment model for evaluating the Jiansanjiang area in Heilongjiang Province, China. The results show that the overall water environment in Jiansanjiang has the following characteristics: "The water quality of farms in the northwest is poor, and the quality of groundwater is better than that of surface water." Total nitrogen (TN) and total phosphorus (TP) in surface water and ammonium nitrogen (NH3-N), ferrum (Fe), and manganese (Mn) in groundwater are the main pollutants. The TP and TN in surface water and the NH3-N in groundwater exceeded the relevant standards, likely due to the excessive application of chemical fertilizers, especially nitrogen fertilizers. Additionally, Fe and Mn are harmful native substances. According to these findings, targeted improvement strategies, such as reducing nitrogen fertilizer application, plugging well, and increasing the surface water utilization rate, are proposed. Moreover, the ChOA-RF model is compared with the traditional empirical value model and the particle swarm optimization-random forest (PSO-RF) model. The results show that the ChOA-RF model can effectively reduce the root mean square error and mean absolute percentage error and improve the coefficient of determination. The running time and convergence ability are also better than those of the PSO-RF model, which is a more accurate and efficient machine learning model. The model can be used not only for high-precision evaluation of regional water environment quality but also for other machine learning fields.

Primary hyperaldosteronism associated with type 3 autoimmune polyendocrine syndrome: A rare case report.

Key Clinical Message: Primary hyperaldosteronism with type 3 autoimmune polyendocrine syndrome was a rare combination of both hyper- and hypoendocrine gland function. Comprehensive treatment including surgery and replacement therapy might be an effective strategy. Abstract: Primary aldosteronism (PA) is a common cause of secondary hypertension originating from hormones. Type 3 autoimmune polyendocrine syndrome (APS-3) is characterized by the simultaneous or subsequent occurrence of autoimmune-mediated endocrine gland damage, except for Addison disease. Here we reported an extremely rare case of a 63-year-old woman with PA and APS-3 who initially presented with hypertension (HT). The APS-3 of this patient mainly exhibited type 1 diabetes mellitus (T1DM) and Hashimoto's thyroiditis. She underwent the adrenal adenoma resection with a histopathologic diagnosis of adrenal cortical adenoma. After surgery, the HT of this patient was immediately reversed, and the concentration of serum potassium went back to normal. Then, this patient was administered with replacement therapy of insulin and levothyroxine sodium tablets (L-T4).

Robot-assisted radical nephroureterectomy using the KangDuo Surgical Robot-01 Sys-tem versus the da Vinci System: a multicenter prospective randomized controlled trial.

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Conventional ultrasonography enabled with augmented reality needle guidance for percutaneous kidney access: An innovative methodologies randomized controlled trial.

IMPORTANCE: Successful needle puncture of the renal collecting system is a critical but difficult procedure in percutaneous nephrolithotomy (PCNL). Although fluoroscopy and ultrasound are the standard imaging techniques to guide puncture during PCNL, both have known limitations. OBJECTIVE: To assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. DESIGN: This study employed a single-center randomized controlled trial (RCT) design to assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. Conducted between May 2021 and November 2021, the trial utilized computer-generated random numbers for participant allocation to control for selection bias. SETTING: The trial was executed at the *********, which serves as an academic medical center. PARTICIPANTS: All patients who met the inclusion criteria were randomly divided into two groups, with 29 patients in each group. One group underwent PCNL procedures using the new navigation system, while the control group underwent standard ultrasound-guided PCNL procedures. Included patients had renal pelvis or caliceal calculi larger than 2.0 cm in diameter or had multiple or staghorn stones. The puncture procedure was performed with the support of real-time ultrasound imaging and visual guidance displayed on the screen. MAIN OUTCOMES AND MEASURES: The primary outcome was system feasibility and puncture success rate. Secondary outcomes included puncture time, total surgical time, number of attempts, post-procedure complications, and one-year and three-year stone recurrence rates. Stone clearance was defined by postoperative CT. Descriptive statistics summarized patient demographics, stone size, and location. Independent samples t-tests analyzed puncture time and total surgical time. Chi-square or Fisher's exact tests compared stone clearance, complications, socioeconomic status, renal hydronephrosis, stone location, race, and medical history. Linear regression examined the correlation between BMI and puncture time. Significance was set at P<0.05. RESULTS: For all 58 patients undergoing PCNL, needle punctures of the renal collecting system were completed with a success rate of 100%. The average time from planning the puncture protocol to successful puncture was significantly shorter in the AcuSee guidance system group (3.12 min, range 0.2-6.88 min) compared to the standard ultrasound-guided group (7.58 min, range 5.41-10.68 min), representing a reduction of approximately 59%. The total surgical time was also shorter in the AcuSee group for patients with no and mild hydronephrosis (P<0.05). Complication rates were lower in the AcuSee group, with no major complications observed. However, 3 patients in the standard ultrasound-guided group have adverse effects after the PCNL procedure. The one-year stone recurrence rate was significantly lower in the AcuSee group (3.4%) compared to the standard group (24.1%), and the three-year recurrence rate was also lower (6.9% vs. 41.4%). Patient-specific factors such as BMI, renal morphology, and prior surgical history did not significantly affect the performance of the AcuSee system. CONCLUSIONS AND RELEVANCE: We report the first clinical application of a new navigation system for needle puncture in ultrasound-guided PCNL. It has been demonstrated that it is feasible and safe compared to the standard ultrasound-guided group in percutaneous renal puncture. This technology provides intuitive and easy-to-use visual guidance, which may facilitate safe, accurate and fast needle puncture of the kidney.

Levothyroxine sodium tablets reversed Hashimoto thyroiditis-induced kidney injury, muscle injury, and lipid metabolism disorder: A case report and literature review.

RATIONALE: Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed. PATIENT CONCERNS, DIAGNOSES, AND INTERVENTIONS: We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate). OUTCOMES AND LESSONS: Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms.

A Study on the Surface Oxidation Pretreatment and Nickel Plating Mechanism of Carbon Fiber.

This study explores the effects of various temperatures on the surface modification of carbon fibers, as well as the effect of differing voltages and currents on the morphology, deposition rate, and thickness of the Ni plating layers. Post-treatment characterization of the samples was conducted utilizing scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) methods, thus facilitating a discussion on the mechanism of Ni plating. The findings demonstrate that at a temperature of 500 °C, the carbon fiber surface exhibits the highest concentration of functional groups, including hydroxyl (-OH), carboxyl (-COOH), and carbonyl (-C=O), resulting in the most efficacious modification. Specifically, exceeding 500 °C leads to significant carbon fiber mass loss, compromising the reinforcement effect. Under a stable voltage of 7.5 V, the Ni-plated layer on the carbon fibers appear smooth, fine, uniform, and complete. Conversely, at a voltage of 15 V, the instantaneous high voltage induces the continuous growth of Ni2+ ions along a singular deposition point, forming a spherical Ni-plated layer. In addition, a current of 0.6 A yields a comparatively uniform and dense carbon fiber coating. Nickel-plated layers on a carbon fiber surface with different morphologies have certain innovative significance for the structural design of composite reinforcements.

Processing of Counterfactual Conditional Sentences with Differential Propositional Truth-Value in Mandarin Chinese: Evidence from ERP.

Although many studies document the role of propositional truth-value in human psychological reading behavior, there is a relative paucity of research examining the role of differential propositional truth-value in processing Chinese counterfactual conditionals. This study is to investigate the role of differential propositional value in processing Chinese counterfactual conditionals by means of ERPs (event-related potentials). The study is based on comprehending two types of Chinese counterfactual conditionals, which is propositional truth value introduced by two different markers of conditional conjunctions in the protasis and apodosis, such as true counterfactual conditional markers jiaru (if) & jiu (so) in the sentence wo xiang yu jiaru you tui jiu keyi zai shuixia zhixi (I think if fish had legs so they could stifle under water), and false counterfactual conditional markers ruguo (if) & namo (then) in the sentence wo xiang gou ruguo you lin namo keyi zai shuixia huxi (I think if dogs had scales, then they could breathe under water). Two counterfactual propositional values (i.e. true and false propositional values) are constructed through manipulating sentence counterfactuality between the true and false counterfactual conditional markers in the protasis and the apodosis. Twenty-four full-time Chinese college students participated in the ERP study. The results demonstrated that processing the true counterfactual propositional sentences with conditional markers jiaru (if) & jiu (so) elicited the N400 effect relative to false propositional sentences with conditional markers ruguo (if) & namo (then). Moreover, the counterfactual sentences with true propositional conditions varied from the elicitation of the N400 effect in the protasis and absence of the N400 effect in the apodosis, showing that semantic roles may gradually disappear under the impact of truth value of propositional counterfactual condition, and/or the roles of semantic anomaly was eliminated in the accumulated sentence processing. While for the false counterfactual conditional sentences, elicitations of P300 in the protasis and robust N400 effect in the apodosis were shown, indicating the increasing semantic role in the processing. Interestingly, there was the absence of the P600 effect for processing sentences with syntactic violation, suggesting little extra syntactic cost in processing sentences with false propositional condition.

Comprehensive treatment of von Hippel-Lindau disease: A case report.

von Hippel-Lindau (VHL) disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular, as well as cysts in other organs. A great clinical treatment strategy is significantly warranted for good prognosis of patients with VHL disease. Herein, we reported a case of a 45-year-old woman diagnosed with VHL disease with spinal hemangioblastoma (HB) and clear cell renal cell carcinoma (ccRCC). Four years after the resection of the right kidney, a recurrent RCC in the right kidney and a malignant lesion in the left kidney were observed. This patient was started on sorafenib (800 mg, daily) and tislelizumab (200 mg per 3 weeks). After 6 months of treatment, the size of renal cell carcinoma was dramatically reduced and renal function improved. More importantly, she achieved partial response during the whole treatment. Microscopically, intramedullary masses resection was done and the HB in T4-5 thoracic spinal was removed. Neurologic symptoms such as numbness and pain were remarkably alleviated. Additionally, tislelizumab-induced elevation in liver transaminase levels and hypothyroidism were revered by hepatoprotector and levothyroxine, respectively. In short, comprehensive treatment strategies may benefit patients with VHL disease, especially with HB and ccRCC.

Renal function after ureteral reconstruction surgery in patients with solitary kidney.

Background: Ureteral strictures (US) could lead to impaired kidney function, which was alleviated by ureteral reconstruction surgery. However, solitary kidney (SK) patients with US were more complicated to treat. This study aimed to evaluate the impact of reconstruction surgery on renal function based on estimated glomerular filtration rate (eGFR) in patients with SK. Methods: We retrospectively enrolled patients who underwent reconstruction surgery between April 2014 to March 2022. eGFR was measured pre- and postoperatively. The 'static renal function' was defined as a change in eGFR of 20% or less at the last follow-up, and the 'worsening renal function group' was defined as a decrease of greater than 20%. Results: A total of 61 SK patients were involved. The success rate of ureteral reconstruction surgery was 90.16% (55/61). The median follow-up time was 20.8 months (range, 3.7-109.2 months). The median eGFR was 65.5 (range, 15.1-99.9) and 65.3 (range, 3.8-123.4) mL/min/1.73 m2 at the baseline and the last follow-up. No statistically significant difference in eGFR was observed between the preoperative baseline and last follow-up visits (P=0.58). However, in patients with baseline renal dysfunction [chronic kidney disease (CKD) stage 3-5], the eGFR significantly improved at the last follow-up compared to the baseline (P=0.02). Three patients developed a 'worsening renal function' (4.92%). Besides, the systolic blood pressures (SBP) at follow-up significantly reduced compared to the preoperative baseline (P=0.002). Conclusions: Ureteral reconstruction surgery is an effective treatment to preserve renal function, which also achieves a high success rate and is associated with the reduction of SBP for SK patients with US.

Heritability of functional gradients in the human subcortico-cortical connectivity.

The human subcortex plays a pivotal role in cognition and is widely implicated in the pathophysiology of many psychiatric disorders. However, the heritability of functional gradients based on subcortico-cortical functional connectivity remains elusive. Here, leveraging twin functional MRI (fMRI) data from both the Human Connectome Project (n = 1023) and the Adolescent Brain Cognitive Development study (n = 936) datasets, we construct large-scale subcortical functional gradients and delineate an increased principal functional gradient pattern from unimodal sensory/motor networks to transmodal association networks. We observed that this principal functional gradient is heritable, and the strength of heritability exhibits a heterogeneous pattern along a hierarchical unimodal-transmodal axis in subcortex for both young adults and children. Furthermore, employing a machine learning framework, we show that this heterogeneous pattern of the principal functional gradient in subcortex can accurately discern the relationship between monozygotic twin pairs and dizygotic twin pairs with an accuracy of 76.2% (P < 0.001). The heritability of functional gradients is associated with the anatomical myelin proxied by MRI-derived T1-weighted/T2-weighted (T1w/T2w) ratio mapping in subcortex. This study provides new insights into the biological basis of subcortical functional hierarchy by revealing the structural and genetic properties of the subcortical functional gradients.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Concentration controlling of carboxylic ester-based electrolyte for low temperature lithium-ion batteries.

Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li+ ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments.

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT.

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated by lactate, can regulate gene expression and participate in disease regulation. However, whether histone lactylation is involved in atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactate-dependent histone H3 lysine 18 lactylation (H3K18la) in vitro and in vivo, as well as in atherosclerotic patients' arteries. Mechanistically, the histone chaperone ASF1A was first identified as a cofactor of P300, which precisely regulated the enrichment of H3K18la at the promoter of SNAI1, thereby activating SNAI1 transcription and promoting EndMT. We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction. Functional analysis based on Apoe KO Asf1a ECKO mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endothelium-specific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development. Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la, SNAI1 transcription, and EndMT-induced atherosclerosis. This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis, which provides emerging therapies for atherosclerosis.

An outbreak of Providencia rettgeri bacteremia at a Ptyas mucosus farm in Hainan, China.

Aim: To describe the histopathology and etiology of an outbreak of respiratory disease at a Ptyas mucosus farm in Hainan, China. Methods and results: The etiology was confirmed by gross examination and microscopic analysis. The bacterial isolates from blood and internal organs were identified by biochemical analysis and 16S rRNA gene sequencing. The virulence and antibiotic resistance characteristics of the isolates were further demonstrated by polymerase chain reaction (PCR), disk diffusion testing, and LD50 analysis in Kunming mice. Histopathological analysis of the diseased P. mucosus revealed systemic lesions, including severe airway obstruction with large numbers of inflammatory cells and cellulose exudates in the lungs; severe multifocal hepatocyte vacuolar degeneration and necrosis in the liver with excessive inflammatory exudates and chronic granuloma; splenic hemorrhage and partial loss of splenic structure; and renal vascular and interstitial congestion. Providencia rettgeri was isolated from the blood and multiple internal organs (liver, spleen, kidneys, and lungs). All examined isolates (H1, H4, and H13) were multidrug-resistant but sensitive to four antibiotics-cefepime, imipenem, chloramphenicol, and ciprofloxacin. Both H1 and H4 carried five resistance genes [bla OXA, tet(A), tet(B), tet(E), and aac (3)-IIa], whereas H13 only carried the tet(A) gene. The dominant virulence pattern of the three isolates was hlyA + ZapA + luxS + rsbA. The virulence of H1 strain was tested, and its 50% lethal dose (LD50) in mice was 2.29 × 108 CFU ml-1. Conclusion: To our knowledge, this is the first study to describe an outbreak of bacteremia caused by P. rettgeri in farmed rat snakes. Significance and impact of the study: The results highlight that P. rettgeri is an emerging bacterial pathogen in farmed reptiles.

Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia.

Schizophrenia (SCZ), which affects approximately 1% of the world's population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

[Robot-assisted laparoscopic ureteroplasty with buccal mucosa graft for complex ureteral stricture].

OBJECTIVE: To investigate the feasibility, safety and effectiveness of robot-assisted laparoscopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture. METHODS: The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted laparoscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology, Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed. Intraoperative conditions, postoperative complications and follow-up data were also recorded and analyzed. RESULTS: The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery. The study included 14 males and 6 females with a mean age of (41±11) years (range: 19 to 60 years) and a mean body mass index of (24.3±3.6) kg/m2 (range: 18.2 to 31.8 kg/m2). There were 9 cases on the left side and 11 cases on the right side. The strictures of all the patients were located in the proximal segment of the ureter (including the ureteropelvic junction). The mean preoperative serum creatinine was (92.2±23.3) µmol/L (range: 49.2 to 138.9 µmol/L), and the mean length of ureteral stricture was (2.8±0.9) cm (range: 1.0 to 4.0 cm). Ten patients had previously undergone unsuccessful reconstructive surgery. During the operation, 12 patients received posteriorly augmented anastomosis with ventral onlay. The mean length of the buccal mucosa graft harvested during the operation was (3.1±0.6) cm (range: 2.0 to 4.3 cm), and the median width was 1.5 cm (range: 1.0 to 2.0 cm). The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases. The median operative time was 154 min (range: 113 to 300 min), and the median estimated blood loss was 45 mL (range: 0 to 100 mL). The median postoperative hospital stay was 4 d (range: 4 to 14 d). The mean postoperative follow-up time was (15.0±1.7) months (range: 12.5 to 17.9 months), and the surgical success rate was 100.0% in this study. After surgery, 11 patients reported mild discomfort at the oral donor site, 2 patients deve-loped urinary tract infection, and no postoperative complications were reported in the other 7 patients. The mean serum creatinine was (90.9±23.9) µmol/L (range: 60.0 to 153.0 µmol/L) six months after surgery. CONCLUSION: Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications, which has shown good feasibility, safety and effectiveness. However, large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.

A multi-classifier system integrated by clinico-histology-genomic analysis for predicting recurrence of papillary renal cell carcinoma.

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.

BSA-stabilized selenium nanoparticles ameliorate intracerebral hemorrhage's-like pathology by inhibiting ferroptosis-mediated neurotoxicology via Nrf2/GPX4 axis activation.

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.