1H-nuclear magnetic resonance analysis reveals dynamic changes in the metabolic profile of patients with severe burns.

Background: Severe burn injury causes a hypermetabolic response, resulting in muscle protein catabolism and multiple organ damage syndrome. However, this response has not yet been continuously characterized by metabolomics in patients. This study aims to quantify temporal changes in the metabolic processes of patients with severe burns. Methods: We employed 1H-nuclear magnetic resonance (NMR) spectroscopy to scrutinize metabolic alterations during the initial 35 days following burn injury in a cohort of 17 adult patients with severe burns, with 10 healthy individuals included as controls. Plasma specimens were collected from patients on postburn days 1, 3, 7, 14, 21, 28 and 35. After performing multivariate statistical analysis, repeated-measures analysis of variance and time-series analysis, we quantified changes in metabolite concentrations. Results: Among the 36 metabolites quantified across 119 samples from burn patients, branched-chain amino acids, glutamate, glycine, glucose, pyruvate, lactate, trimethylamine N-oxide and others exhibited obvious temporal variations in concentration. Notably, these metabolites could be categorized into three clusters based on their temporal characteristics. The initial response to injury was characterized by changes in lactate and amino acids, while later changes were driven by an increase in fatty acid catabolism and microbial metabolism, leading to the accumulation of ketone bodies and microbial metabolites. Conclusions: Metabolomics techniques utilizing NMR have the potential to monitor the intricate processes of metabolism in patients with severe burns. This study confirmed that the third day after burn injury serves as the boundary between the ebb phase and the flow phase. Furthermore, identification of three distinct temporal patterns of metabolites revealed the intrinsic temporal relationships between these metabolites, providing clinical data for optimizing therapeutic strategies.

Computer-aided diagnostic system with automated deep learning method based on the AutoGluon framework improved the diagnostic accuracy of early esophageal cancer.

Background: There have been studies on the application of computer-aided diagnosis (CAD) in the endoscopic diagnosis of early esophageal cancer (EEC), but there is still a significant gap from clinical application. We developed an endoscopic CAD system for EEC based on the AutoGluon framework, aiming to explore the feasibility of automatic deep learning (DL) in clinical application. Methods: The endoscopic pictures of normal esophagus, esophagitis, and EEC were collected from The First Affiliated Hospital of Soochow University (September 2015 to December 2021) and the Norwegian HyperKvasir database. All images of non-cancerous esophageal lesions and EEC in this study were pathologically examined. There were three tasks: task A was normal vs. lesion classification under non-magnifying endoscopy (n=932 vs. 1,092); task B was non-cancer lesion vs. EEC classification under non-magnifying endoscopy (n=594 vs. 429); and task C was non-cancer lesion vs. EEC classification under magnifying endoscopy (n=505 vs. 824). In all classification tasks, we took 100 pictures as the verification set, and the rest comprised as the training set. The CAD system was established based on the AutoGluon framework. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior >15 years; junior <5 years). Model evaluation indicators included accuracy, recall rate, precision, F1 value, interpretation time, and the area under the receiver operating characteristic (ROC) curve (AUC). Results: In tasks A and B, the accuracies of medium-performance CAD and high-performance CAD were lower than those of junior doctors and senior doctors. In task C, the medium-performance and high-performance CAD accuracies were close to those of junior doctors and senior doctors. The high-performance CAD model outperformed the junior doctors in both task A (0.850 vs. 0.830) and task C (0.840 vs. 0.830) in sensitivity comparison, but there was still a large gap between high-performance CAD models and doctors in sensitivity comparison. In task A, with the aid of CAD pre-interpretation, the accuracy of junior and senior physicians were significantly improved (from 0.880 to 0.915 and from 0.920 to 0.945, respectively); the time spent on film reading was significantly shortened (junior: from 11.3 to 8.7 s; senior: from 6.7 to 5.5 s). In task C, with the aid of CAD pre-interpretation, the accuracy of junior and senior physicians were significantly improved (from 0.850 to 0.865 and from 0.915 to 0.935, respectively); the reading time was significantly shortened (junior: from 9.5 to 7.7 s; senior: from 5.6 to 3.0 s). Conclusions: The CAD system based on the AutoGluon framework can assist doctors to improve the diagnostic accuracy and reading time of EEC under endoscopy. This study reveals that automatic DL methods are promising in clinical application.

Prognostic value of geriatric nutritional risk index in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. METHODS: This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. RESULTS: The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI < 98 group (HR 0.04, 95% CI 0.00, 0.89). ROC analysis showed that the baseline GNRI had a very high predictive performance for all-cause death (AUC = 0.8844), and the predictive threshold was 98.62; additionally, in the RCS regression analysis and piecewise linear regression analysis we found that the threshold point for the GNRI-related all-cause death risk was 98.28 and the risk will be significantly reduced when the subjects' baseline GNRI was greater than 98.28. CONCLUSIONS: GNRI level at admission was an independent predictor of all-cause death in SCAD patients after PCI, and GNRI equal to 98.28 may be a useful threshold for nutritional intervention in SCAD patients treated with PCI.

New-generation advanced PROTACs as potential therapeutic agents in cancer therapy.

Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit the endogenous E3 ubiquitin ligases to facilitate degradation of the proteins of interest (POIs) through the ubiquitin-proteasome system (UPS) in a cyclic catalytic manner. Despite recent endeavors to advance the utilization of PROTACs in clinical settings, the majority of PROTACs fail to progress beyond the preclinical phase of drug development. There are multiple factors impeding the market entry of PROTACs, with the insufficiently precise degradation of favorable POIs standing out as one of the most formidable obstacles. Recently, there has been exploration of new-generation advanced PROTACs, including small-molecule PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, to improve the in vivo efficacy of PROTACs. These improved PROTACs possess the capability to mitigate undesirable physicochemical characteristics inherent in traditional PROTACs, thereby enhancing their targetability and reducing off-target side effects. The new-generation of advanced PROTACs will mark a pivotal turning point in the realm of targeted protein degradation. In this comprehensive review, we have meticulously summarized the state-of-the-art advancements achieved by these cutting-edge PROTACs, elucidated their underlying design principles, deliberated upon the prevailing challenges encountered, and provided an insightful outlook on future prospects within this burgeoning field.

Efficacy and Safety of Ultrasound-Guided Acupotomy Versus Celecoxib in Patients with Thoracodorsal Myofascial Pain Syndrome: A Randomized Controlled Trial.

Objective: To evaluate the efficacy and safety of ultrasound-guided acupotomy (UgA) for the treatment of thoracodorsal myofascial pain syndrome (TDMPS) and monitor its mid-term efficacy at 3 months after treatment. Methods: A 3-week, evaluator-blinded randomized clinical trial was conducted among 100 patients with TDMPS (visual analogue scale [VAS] score > 3) in the outpatient clinic of the Department of Orthopaedics of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, with a 3-month follow-up starting after completion of treatment. These patients were randomly assigned to receive UgA (n = 50) or oral celecoxib (n = 50). Recruitment was conducted between January 2021 and July 2022. The primary outcome was the VAS score, and the secondary outcomes included the Oswestry Disability Index (ODI), Pain Anxiety Symptoms Scale (PASS), and TNF-α and IL-1ß levels. Outcome data were collected at baseline, week 3 (post-treatment) and week 15 (follow-up). Results: Compared with that in the celecoxib group, the pain in the UgA group was alleviated more strongly, with an adjusted mean group difference of -0.69 (95% CI,-1.07 to -0.31 after multiple imputation) at week 3 and -1.96 (95% CI,-2.33 to -1.59 after multiple imputation) at week 15 (p < 0.001 for overall group × time interaction). Both groups exhibited improvements in the ODI and PASS scores at weeks 3 and 15, but these improvements were significantly greater in the UgA group (p < 0.05). At week 3, the TNF-α and IL-1 levels were significantly lower in both groups, but celecoxib was more effective (p < 0.05). Results from analyses with multilevel multiple imputation for missingness were similar. Conclusion: UgA led to greater and safer alleviation of pain, dysfunction, and pain anxiety in patients treated with TDMPS than did celecoxib and had a durable 3-month efficacy but was inferior to celecoxib in reducing the level of inflammatory factors. These findings may prompt clinicians to recommend UgA as an alternative and supplementary therapy for pain management in patients with TDMPS.

Catalytically Relevant Organocopper(III) Complexes Formed through Aryl-Radical-Enabled Oxidative Addition.

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation of these fundamental steps remain elusive owing largely to the typically slow oxidative addition rate of copper(I) complexes and the instability of the copper(III) species. We report herein a novel aryl-radical-enabled stepwise oxidative addition pathway that allows for the formation of well-defined alkyl-CuIII species from CuI complexes. The process is enabled by the SET from a CuI species to an aryl diazonium salt to form a CuII species and an aryl radical. Subsequent iodine abstraction from an alkyl iodide by the aryl radical affords an alkyl radical, which then reacts with the CuII species to form the alkyl-CuIII complex. The structure of resultant [(bpy)CuIII(CF3)2(alkyl)] complexes has been characterized by NMR spectroscopy and X-ray crystallography. Competition experiments have revealed that the rate at which different alkyl iodides undergo oxidative addition is consistent with the rate of iodine abstraction by carbon-centered radicals. The CuII intermediate formed during the SET process has been identified as a four-coordinate complex, [CuII(CH3CN)2(CF3)2], through electronic paramagnetic resonance (EPR) studies. The catalytic relevance of the high-valent organo-CuIII has been demonstrated by the C-C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis of these formal CuIII complexes indicates inverted ligand fields in σ(Cu-CH2) bonds. These results demonstrate the stepwise oxidative addition in copper catalysis and provide a general strategy to investigate the elusive formal CuIII complexes.

Intracranial aneurysm circulating exosome-derived LncRNA ATP1A1-AS1 promotes smooth muscle cells phenotype switching and apoptosis.

Exosomal long non-coding RNAs (LncRNAs) play a crucial role in the pathogenesis of cerebrovascular diseases. However, the expression profiles and functional significance of exosomal LncRNAs in intracranial aneurysms (IAs) remain poorly understood. Through high-throughput sequencing, we identified 1303 differentially expressed LncRNAs in the plasma exosomes of patients with IAs and healthy controls. Quantitative real-time polymerase chain reaction (qRT-PCR) verification confirmed the differential expression of LncRNAs, the majority of which aligned with the sequencing results. ATP1A1-AS1 showed the most significant upregulation in the disease group. Importantly, subsequent in vitro experiments validated that ATP1A1-AS1 overexpression induced a phenotype switching in vascular smooth muscle cells, along with promoting apoptosis and upregulating MMP-9 expression, potentially contributing to IAs formation. Furthermore, expanded-sample validation affirmed the high diagnostic value of ATP1A1-AS1. These findings suggest that ATP1A1-AS1 is a potential therapeutic target for inhibiting IAs progression and serves as a valuable clinical diagnostic marker.

Postoperative Lenvatinib plus PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with MVI (BCLC 0-A): A Propensity Score Matching Analysis.

PURPOSE: This research seeks to determine the effectiveness of post-operative adjuvant lenvatinib plus PD-1 blockade for early-stage HCC patients with microvascular invasion (MVI). METHODS: 393 HCC patients (Barcelona Clinic Liver Cancer stage 0-A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to inclusion and exclusion criteria and assigned to two groups: surgery alone (Surgery-alone) and surgery with lenvatinib and PD-1 blockade (Surgery+Len+PD-1) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate following the application of propensity score matching (PSM). The Cox proportional hazards model was utilized for univariate and multivariate analysis. RESULTS: 99 matched pairs were selected using PSM. Patients in the Surgery+Len+PD-1 group had significantly higher three-year RFS (76.8%, 65.7%, and 53.5%) compared to patients in the Surgery-alone group (60.6%, 45.5%, and 37.4%) (P=0.012). The two groups showed no significant differences in recurrence types and OS. Surgery-alone, MVI-M2, and AFP≥200ng/mL were independent risk factors for RFS (P<0.05), and history of alcoholism was an independent risk factor for OS (P=0.022). CONCLUSIONS: Postoperative lenvatinib plus PD-1 blockade improved the RFS in HCC patients with MVI and was particularly beneficial for specific individuals.

Diagnostic Performance of [18F]AlF-Thretide PET/CT in Patients with Newly Diagnosed Prostate Cancer Using Histopathology as Reference Standard.

This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E-02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score-predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.

Interfacial Reactions between Sn-Based Solders and n-Type Bi2(Te,Se)3 Thermoelectric Material.

This study investigated the interfacial reactions between n-type Bi2(Te,Se)3 thermoelectric material, characterized by a highly-oriented (110) plane, and pure Sn and Sn-3.0Ag-0.5Cu (wt.%) solders, respectively. At 250 °C, the liquid-state Sn/Bi2(Te,Se)3 reactions resulted in the formation of both SnTe and BiTe phases, with Bi-rich particles dispersed within the SnTe phase. The growth of the SnTe phase exhibited diffusion-controlled parabolic behavior over time. In contrast, the growth rate was considerably slower compared to that observed with p-type (Bi,Sb)2Te3. Solid-state Sn/Bi2(Te,Se)3 reactions conducted between 160 °C and 200 °C exhibited similar interfacial microstructures. The SnTe phase remained the primary reaction product, embedded with tiny Bi-rich particles, revealing a diffusion-controlled growth. However, the BiTe layer had no significant growth. Further investigation into growth kinetics of intermetallic compounds and microstructural evolution was conducted to elucidate the reaction mechanism. The slower growth rates in Bi2(Te,Se)3, compared to the reactions with (Bi,Sb)2Te3, could be attributed to the strong suppression effect of Se on SnTe growth. Additionally, the interfacial reactions of Bi2(Te,Se)3 with Sn-3.0Ag-0.5Cu were also examined, showing similar growth behavior to those observed with Sn solder. Notably, compared with Ag, Cu tends to diffuse towards the interfacial reaction phases, resulting in a high Cu solubility within the SnTe phase.

Dichotomous transactivation domains contribute to growth inhibitory and promotion functions of TAp73.

The transcription factor p73, a member of the p53 tumor-suppressor family, regulates cell death and also supports tumorigenesis, although the mechanistic basis for the dichotomous functions is poorly understood. We report here the identification of an alternate transactivation domain (TAD) located at the extreme carboxyl (C) terminus of TAp73ß, a commonly expressed p73 isoform. Mutational disruption of this TAD significantly reduced TAp73ß's transactivation activity, to a level observed when the amino (N)-TAD that is similar to p53's TAD, is mutated. Mutation of both TADs almost completely abolished TAp73ß's transactivation activity. Expression profiling highlighted a unique set of targets involved in extracellular matrix-receptor interaction and focal adhesion regulated by the C-TAD, resulting in FAK phosphorylation, distinct from the N-TAD targets that are common to p53 and are involved in growth inhibition. Interestingly, the C-TAD targets are also regulated by the oncogenic, amino-terminal-deficient DNp73ß isoform. Consistently, mutation of C-TAD reduces cellular migration and proliferation. Mechanistically, selective binding of TAp73ß to DNAJA1 is required for the transactivation of C-TAD target genes, and silencing DNAJA1 expression abrogated all C-TAD-mediated effects. Taken together, our results provide a mechanistic basis for the dichotomous functions of TAp73 in the regulation of cellular growth through its distinct TADs.

The effect of student-perceived teacher support on math anxiety: chain mediation of teacher-student relationship and math self-efficacy.

Introduction: This study investigates the mechanisms linking students' perceived teacher support with math anxiety, focusing on the mediating roles of the teacher-student relationship and mathematics self-efficacy. Methods: The research was conducted with 401 fifth-grade students in China, utilizing scales for Students' Perceived Teacher Support, Teacher-Student Relationship, Math Self-Efficacy, and Math Anxiety. Results: Findings revealed that student-perceived math teacher support, teacher-student relationship, and math self-efficacy were all significantly negatively correlated with math anxiety. It was notably found that student-perceived math teacher support influenced math anxiety through the chain mediation of teacher-student relationship and math self-efficacy. Additionally, the effect of students' perceived emotional support from math teachers on math anxiety, mediated by teacher-student relationship intimacy, was significant only among male students. Discussion: These results underscore the importance of fostering positive teacher-student interactions and enhancing self-efficacy to reduce math anxiety among primary school students. The gender-specific findings regarding emotional support and relationship intimacy highlight the need for tailored strategies in addressing math anxiety.

Verteporfin suppressed mitophagy via PINK1/parkin pathway in endometrial cancer.

Endometrial cancer (EC) is a malignancy that poses a threat to woman's health worldwide. Building upon prior work, we explored the inhibitory effect of verteporfin on EC. We showed that verteporfin can damage the mitochondria of EC cells, leading to a decrease of mitochondrial membrane potential and an increase in ROS (reactive oxygen species). In addition, verteporfin treatment was shown to inhibit the proliferation and migration of EC cells, promote apoptosis, and reduce the expression of mitophagy-related proteins PINK1/parkin and TOM20. The ROS inhibitor N-Acetyl Cysteine was able to rescue the expression of PINK1/parkin proteins. This suggests that verteporfin may inhibit mitophagy by elevating ROS levels, thereby inhibiting EC cell viability. The effect of verteporfin on mitophagy supports further investigation as a potential therapeutic option for EC.

Electropolymerization of a Carbonyl-Modified Dihydropyrazine Derivative for Aqueous Zinc Batteries with Ultrahigh Cycling Stability.

The design of aqueous zinc-ion batteries (ZIBs) that have high specific capacity and long-term stability is essential for future large-scale energy storage systems. Cathode materials with extended π-conjugation and abundant active sites are desirable to enhance the charge storage performance and the cycling stability of the aqueous ZIB. Based on this concept, 6,9-dihydropyrazino[2,3-g]quinoxaline-2,3,7,8(1H,4H)-tetrone was chosen as the monomer to be electropolymerized onto carbon cloth (PDHPQ-Tetrone/CC). When used as the cathode material for aqueous ZIBs, an exceptional cycling life (>20,000 cycles) at a current density of 10 A g-1 was achieved, with the specific capacity maintained at 82.8% and with the Coulombic efficiency at around 100% throughout cycling. At the charge-discharge current density of 0.1 A g-1, the ZIB with PDHPQ-Tetrone/CC achieved a high specific capacity of 248 mAh g-1. Kinetic analyses showed that both surface-capacitive-controlled processes and semi-infinite diffusion-controlled processes contribute to the stored charge. The charge storage mechanism was investigated with ex situ characterizations and involves the redox processes of carbonyl/hydroxyl and amino/imino groups coupled with insertion and extraction of both Zn2+ and H+.

The efficacy of electroacupuncture for cervical nerve edema and movement disorder caused by the brachial plexus injury: a case report.

The brachial plexus injury (BPI) is one of the most severe types of peripheral nerve injuries, often caused by upper limb traction injury. In clinic, the surgery is widely used to treat the BPI. However, surgery may need to be performed multiple times at different stages, which carries risks and brings heavy economic burden. In non-surgical treatment, splinting, local injection of corticosteroids, and oral corticosteroids can achieve significant short-term benefits, but they are prone to recurrence and may cause complications of mechanical or chemical nerve damage. In this report, we present a case of a 46-year-old female patient with BPI. The patient had difficulty in raising, flexing and extending of the left upper limb, and accompanied with the soreness and pain of neck and shoulder. After 3 months of EA treatment, a significant reduction in the inner diameter of the left C5 to C7 root at the outlet of brachial plexus nerve was detected by musculoskeletal ultrasound, and the soreness and pain in the left neck and shoulder were significantly reduced. The soreness and pain in the left neck and shoulder did not recur for 2 years. Case summary: The patient is a 46-year-old female with BPI. She experienced difficult in lifting, flexing and extending of the left upper limb, which accompanied by soreness and pain in the left neck and shoulder. After 3 months of EA treatment, the patient's pain and limb's movement disorder was improved. After 2 years of follow-up, the patient's left neck and shoulder showed no further pain. Conclusion: EA has shown satisfied efficacy in BPI, improving limb restrictions and relieving pain in patients for at least 2 years.

STAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to promote tumor growth.

SCAP plays a central role in controlling lipid homeostasis by activating SREBP-1, a master transcription factor in controlling fatty acid (FA) synthesis. However, how SCAP expression is regulated in human cancer cells remains unknown. Here, we revealed that STAT3 binds to the promoter of SCAP to activate its expression across multiple cancer cell types. Moreover, we identified that STAT3 also concurrently interacts with the promoter of SREBF1 gene (encoding SREBP-1), amplifying its expression. This dual action by STAT3 collaboratively heightens FA synthesis. Pharmacological inhibition of STAT3 significantly reduces the levels of unsaturated FAs and phospholipids bearing unsaturated FA chains by reducing the SCAP-SREBP-1 signaling axis and its downstream effector SCD1. Examination of clinical samples from patients with glioblastoma, the most lethal brain tumor, demonstrates a substantial co-expression of STAT3, SCAP, SREBP-1, and SCD1. These findings unveil STAT3 directly regulates the expression of SCAP and SREBP-1 to promote FA synthesis, ultimately fueling tumor progression.

The role of cochlear and vestibular afferents in long-latency cervical vestibular evoked myogenic potentials.

OBJECTIVE: To examine the origin of cervical vestibular evoked myogenic potential (cVEMP) late waves (n34-p44) elicited with air-conducted click stimuli. DESIGN: Using a retrospective design, cVEMPs from normal volunteers were compared to those obtained from patients with vestibular and auditory pathologies. STUDY SAMPLE: (1) Normal volunteers (n = 56); (2) severe-to-profound sensorineural hearing loss (SNHL) with normal vestibular function (n = 21); (3) peripheral vestibular impairment with preserved hearing (n = 16); (4) total vestibulocochlear deficit (n = 23). RESULTS: All normal volunteers had ipsilateral-dominant early p13-n23 peaks. Late peaks were present bilaterally in 78%. The p13-n23 response was present in all patients with SNHL but normal vestibular function, and 43% had late waves. Statistical comparison of these patients to a subset of age-matched controls showed no significant difference in the frequencies, amplitudes or latencies of their ipsilateral early and late peaks. cVEMPs were absent in all patients with vestibular impairment. CONCLUSION: The presence of long-latency cVEMP waves was not dependent on the integrity of sensorineural hearing pathways, but instead correlated with intact vestibular function. This finding conflicts with the view that these late waves are cochlear in origin, and suggests that vestibular afferents may assume a more prominent role in their generation.

Boron modification promoting electrochemical surface reconstruction of NiFe-LDH for efficient and stable freshwater/seawater oxidation catalysis.

Transition metal-based electrocatalysts generally take place surface reconstruction in alkaline conditions, but little is known about how to improve the reconstruction to a highly active oxyhydroxide surface for an efficient and stable oxygen evolution reaction (OER). Herein, we develop a strategy to accelerate surface reconstruction by combining boron modification and cyclic voltammetry (CV) activation. Density functional theory calculations and in-situ/ex-situ characterizations indicate that both B-doping and electrochemical activation can reduce the energy barrier and contribute to the surface evolution into highly active oxyhydroxides. The formed oxyhydroxide active phase can tune the electronic configuration and boost the OER process. The reconstructed catalyst of CV-B-NiFe-LDH displays excellent alkaline OER performance in freshwater, simulated seawater, and natural seawater with low overpotentials at 100 mA cm-2 (η100: 219, 236, and 255 mV, respectively) and good durability. This catalyst also presents outstanding Cl- corrosion resistance in alkalized seawater electrolytes. The CV-B-NiFe-LDH||Pt/C electrolyzer reveals prominent performance for alkalized freshwater/seawater splitting. This study provides a guideline for developing advanced OER electrocatalysts by promoting surface reconstruction.

An extensive analysis of the prognostic and immune role of FOXO1 in various types of cancer.

Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.

Overcoming strength-ductility tradeoff with high pressure thermal treatment.

Conventional material processing approaches often achieve strengthening of materials at the cost of reduced ductility. Here, we show that high-pressure and high-temperature (HPHT) treatment can help overcome the strength-ductility trade-off in structural materials. We report an initially strong-yet-brittle eutectic high entropy alloy simultaneously doubling its strength to 1150 MPa and its tensile ductility to 36% after the HPHT treatment. Such strength-ductility synergy is attributed to the HPHT-induced formation of a hierarchically patterned microstructure with coherent interfaces, which promotes multiple deformation mechanisms, including dislocations, stacking faults, microbands and deformation twins, at multiple length scales. More importantly, the HPHT-induced microstructure helps relieve stress concentration at the interfaces, thereby arresting interfacial cracking commonly observed in traditional eutectic high entropy alloys. These findings suggest a new direction of research in employing HPHT techniques to help develop next generation structural materials.