The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia.

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Ultrasound-based nomogram to predict the recurrence in papillary thyroid carcinoma using machine learning.

BACKGROUND AND AIMS: The recurrence of papillary thyroid carcinoma (PTC) is not unusual and associated with risk of death. This study is aimed to construct a nomogram that combines clinicopathological characteristics and ultrasound radiomics signatures to predict the recurrence in PTC. METHODS: A total of 554 patients with PTC who underwent ultrasound imaging before total thyroidectomy were included. Among them, 79 experienced at least one recurrence. Then 388 were divided into the training cohort and 166 into the validation cohort. The radiomics features were extracted from the region of interest (ROI) we manually drew on the tumor image. The feature selection was conducted using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. And multivariate Cox regression analysis was used to build the combined nomogram using radiomics signatures and significant clinicopathological characteristics. The efficiency of the nomogram was evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to analyze the recurrence-free survival (RFS) in different radiomics scores (Rad-scores) and risk scores. RESULTS: The combined nomogram demonstrated the best performance and achieved an area under the curve (AUC) of 0.851 (95% CI: 0.788 to 0.913) in comparison to that of the radiomics signature and the clinical model in the training cohort at 3 years. In the validation cohort, the combined nomogram (AUC = 0.885, 95% CI: 0.805 to 0.930) also performed better. The calibration curves and DCA verified the clinical usefulness of combined nomogram. And the Kaplan-Meier analysis showed that in the training cohort, the cumulative RFS in patients with higher Rad-score was significantly lower than that in patients with lower Rad-score (92.0% vs. 71.9%, log rank P < 0.001), and the cumulative RFS in patients with higher risk score was significantly lower than that in patients with lower risk score (97.5% vs. 73.5%, log rank P < 0.001). In the validation cohort, patients with a higher Rad-score and a higher risk score also had a significantly lower RFS. CONCLUSION: We proposed a nomogram combining clinicopathological variables and ultrasound radiomics signatures with excellent performance for recurrence prediction in PTC patients.

Deletion of Bmal1 in aggrecan-expressing cells leads to mouse temporomandibular joint osteoarthritis.

INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer.

OBJECTIVE: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). METHODS: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. RESULTS: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%). CONCLUSIONS: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.

Bidirectional Copy-Paste Mamba for Enhanced Semi-Supervised Segmentation of Transvaginal Uterine Ultrasound Images.

Automated perimetrium segmentation of transvaginal ultrasound images is an important process for computer-aided diagnosis of uterine diseases. However, ultrasound images often contain various structures and textures, and these structures have different shapes, sizes, and contrasts; therefore, accurately segmenting the parametrium region of the uterus in transvaginal uterine ultrasound images is a challenge. Recently, many fully supervised deep learning-based methods have been proposed for the segmentation of transvaginal ultrasound images. Nevertheless, these methods require extensive pixel-level annotation by experienced sonographers. This procedure is expensive and time-consuming. In this paper, we present a bidirectional copy-paste Mamba (BCP-Mamba) semi-supervised model for segmenting the parametrium. The proposed model is based on a bidirectional copy-paste method and incorporates a U-shaped structure model with a visual state space (VSS) module instead of the traditional sampling method. A dataset comprising 1940 transvaginal ultrasound images from Tongji Hospital, Huazhong University of Science and Technology is utilized for training and evaluation. The proposed BCP-Mamba model undergoes comparative analysis with two widely recognized semi-supervised models, BCP-Net and U-Net, across various evaluation metrics including Dice, Jaccard, average surface distance (ASD), and Hausdorff_95. The results indicate the superior performance of the BCP-Mamba semi-supervised model, achieving a Dice coefficient of 86.55%, surpassing both U-Net (80.72%) and BCP-Net (84.63%) models. The Hausdorff_95 of the proposed method is 14.56. In comparison, the counterparts of U-Net and BCP-Net are 23.10 and 21.34, respectively. The experimental findings affirm the efficacy of the proposed semi-supervised learning approach in segmenting transvaginal uterine ultrasound images. The implementation of this model may alleviate the expert workload and facilitate more precise prediction and diagnosis of uterine-related conditions.

Association between blood lead levels and parathyroid hormone among United States adolescents aged 12-19: a cross-sectional study.

Aims: Studies on the association between serum lead levels and parathyroid function in adolescents are lacking. Therefore, in this study, we elucidated the possible association between blood lead levels (BLLs) and the parathyroid hormone (PTH) in adolescents aged 12-19 years in the United States. Methods: In this study, information from the database of the National Health and Nutrition Examination Survey was utilized. The study included 3919 participants from survey cycles between 2003-2004 and 2005-2006. Multivariable linear regression analysis was performed to determine the correlation between BLLs and PTH. Furthermore, smooth curve fitting was utilized to analyze the dose-response relationship between BLLs and PTH. Results: Multivariable linear regression analysis revealed that every 1 µg/dL increase in BLLs was associated with 0.67 pg/mL increase in PTH (ß = 0.67, 95% CI: 0.16-1.18, p < 0.01). However, sex-stratified subgroup analysis revealed that this positive association was only observed in males (ß = 1.16, 95% CI: 0.50-1.83 p < 0.01). Smooth curve fitting revealed a positive correlation between BLLs and PTH. Conclusions: In adolescents in the United States, BLLs are positively correlated with PTH, particularly in males.

ChatGPT compared to national guidelines for management of ovarian cancer: Did ChatGPT get it right? - A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: We evaluated the performance of a chatbot compared to the National Comprehensive Cancer Network (NCCN) Guidelines for the management of ovarian cancer. METHODS: Using NCCN Guidelines, we generated 10 questions and answers regarding management of ovarian cancer at a single point in time. Questions were thematically divided into risk factors, surgical management, medical management, and surveillance. We asked ChatGPT (GPT-4) to provide responses without prompting (unprompted GPT) and with prompt engineering (prompted GPT). Responses were blinded and evaluated for accuracy and completeness by 5 gynecologic oncologists. A score of 0 was defined as inaccurate, 1 as accurate and incomplete, and 2 as accurate and complete. Evaluations were compared among NCCN, unprompted GPT, and prompted GPT answers. RESULTS: Overall, 48% of responses from NCCN, 64% from unprompted GPT, and 66% from prompted GPT were accurate and complete. The percentage of accurate but incomplete responses was higher for NCCN vs GPT-4. The percentage of accurate and complete scores for questions regarding risk factors, surgical management, and surveillance was higher for GPT-4 vs NCCN; however, for questions regarding medical management, the percentage was lower for GPT-4 vs NCCN. Overall, 14% of responses from unprompted GPT, 12% from prompted GPT, and 10% from NCCN were inaccurate. CONCLUSIONS: GPT-4 provided accurate and complete responses at a single point in time to a limited set of questions regarding ovarian cancer, with best performance in areas of risk factors, surgical management, and surveillance. Occasional inaccuracies, however, should limit unsupervised use of chatbots at this time.

A Room-Temperature All-Solid-State Na-Ag Battery with a Long Cycle Life and Low Overpotential.

Aqueous Zn-Ag batteries have been developed and commercialized for nearly a century, offering stable discharge and high specific energies. Sodium, with its lower redox potential, smaller charge-to-mass ratio, and abundant resources, presents a promising alternative to zinc. In this study, we successfully developed an all-solid-state Na-Ag battery system. This battery demonstrates stable discharge and charge voltages, low overpotential (0.27 V), high energy efficiency (>91%), and long cycle life under moderate humidity at room temperature. The reaction mechanism was elucidated through combined analyses using differential electrochemical mass spectrometry (DEMS), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Our findings indicate that metallic Ag in the cathode materials acts as an effective catalyst for the oxygen reduction reaction during the initial discharge process, forming NaOH as the discharge product. Ag is then oxidized during the charging process and recovered during discharge, serving as an active reactant in the Na-Ag battery. This work demonstrates superior performance of all-solid-state Na-Ag battery over aqueous Zn-Ag battery. Na-Ag battery may be of interest in applications with stringent requirements on stable discharge voltage and high specific energy.

A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score): a Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery. METHODS: We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated. Five-fold cross-validation was applied to the multivariate model. Significant variables were assigned a 'BLOODS' (BLood transfusion Over an Ovarian cancer Debulking Surgery) score of +1 if present. A total BLOODS score was calculated for each patient, and the odds of receiving a transfusion was determined for each score. RESULTS: Overall, 1566 patients met eligibility criteria; 800 (51%) underwent a peri-operative blood transfusion. Odds ratios (OR) were statistically significant for American Society of Anesthesiologists scores of 3 and 4 (OR 1.34, 95% confidence interval (95% CI) 1.09 to 1.63), pre-operative levels of cancer antigen 125 (CA125) (OR 2.43, 95% CI 1.98 to 2.99), platelets (OR 1.59, 95% CI 1.45 to 1.74), obesity (OR 0.76, 95% CI 0.60 to 0.96), presence of carcinomatosis (OR 2.45, 95% CI 1.93 to 3.11), bulky upper abdominal disease (OR 2.86, 95% CI 2.32 to 3.54), pre-operative serum albumin level (OR 0.31, 95% CI 0.24 to 0.40), and pre-operative hemoglobin level (OR 0.56, 95% CI 0.51 to 0.61). The corrected AUC was 0.748 (95% CI 0.693 to 0.804). BLOODS scores of 0 and 5 corresponded to 11% and 73% odds, respectively, of receiving a peri-operative blood transfusion. CONCLUSIONS: We developed a universal pre-operative scoring system, the BLOODS score, to help identify patients with ovarian cancer who would benefit from surgical planning and blood-saving techniques. The BLOODS score was directly proportional to the American Society of Anesthesiologists score, presence of upper abdominal disease, carcinomatosis, CA125 level, and platelets level. We believe this model can help physicians with surgical planning and can benefit patient outcomes.

Comprehensive analysis of adverse events associated with pimavanserin using the FAERS database.

OBJECTIVE: Pimavanserin, a novel 5-HT2A receptor antagonist, has been approved for the treatment of Parkinson's disease psychosis (PDP). This study aims to conduct a comprehensive analysis of the adverse events (AEs) of pimavanserin by analyzing the FDA's Adverse Event Reporting System (FAERS) database. METHODS: AE reports related to pimavanserin in the FAERS database from the second quarter of 2016 to the fourth quarter of 2023 were mined. Signal detection methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were employed to identify and classify AEs. RESULTS: The study collected 12,839,687 AE reports, with 30,997 reports primarily suspecting pimavanserin, identifying 166 Preferred Terms (PTs) across 27 System Organ Classes (SOCs). The data showed that males reported more frequently than females, with the highest reporting in patients aged 75 and above. Reports increased over time, with a significant rise in 2023 compared to 2016. Major categories of AEs included hallucination, death, product dose omission issue, and confusional state, with death being notably the second most reported issue. Strong and new potential AEs were identified, including sleep-related issues like somnolence, insomnia, and sleep talking; cognitive and behavioral issues such as alexithymia, belligerence, and aggression; dose-related issues like prescribed underdose and underdose; and other AEs like nonspecific reactions. CONCLUSION: This study reveals potential AEs of pimavanserin, including sleep disorders and cognitive changes, underscoring the importance of careful monitoring and personalized treatment in managing PDP.

Learning obstacle avoidance and predation in complex reef environments with deep reinforcement learning.

The reef ecosystem plays a vital role as a habitat for fish species with limited swimming capabilities, serving not only as a sanctuary and food source but also influencing their behavioral tendencies. Understanding the intricate mechanism through which fish adeptly navigate the moving targets within reef environments within complex water flow, all while evading obstacles and maintaining stable postures, has remained a challenging and prominent subject in the realms of fish behavior, ecology, and biomimetics alike. An integrated simulation framework is used to investigate fish predation problems within intricate environments, combining deep reinforcement learning algorithms (DRL) with high-precision fluid-structure interaction numerical methods-lmmersed Boundary Lattice Boltzmann Method (lB-LBM). The Soft Actor-Critic (SAC) algorithm is used to improve the intelligent fish's capacity for random exploration, tackling the multi-objective sparse reward challenge inherent in real-world scenarios. Additionally, a reward shaping method tailored to its action purposes has been developed, capable of capturing outcomes and trend characteristics effectively. The convergence and robustness advantages of the method elucidated in this paper are showcased through two case studies: one addressing fish capturing randomly moving targets in hydrostatic flow field, and the other focusing on fish counter-current foraging in reef environments to capture drifting food. A comprehensive analysis was conducted of the influence and significance of various reward types on the decision-making processes of intelligent fish within intricate environments.

Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports.

OBJECTIVE: Daridorexant, a novel dual orexin receptor antagonist, was approved by the FDA in 2022 for the treatment of insomnia in adults. The aim of this study is to delve into the adverse events (AEs) of daridorexant by analyzing data from the FAERS database, to assess its safety and effectiveness in clinical applications. METHODS: This study selected data from the FAERS database from the first quarter of 2022 to the third quarter of 2023. Various data analysis methods were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), to assess AEs related to daridorexant. RESULTS: The study analyzed a total of 2,624,030 AE reports, of which 1318 were related to daridorexant. It identified 59 preferred terms (PTs) involving 23 system organ classes (SOCs). Signal mining identified new potential AEs related to daridorexant, including sleep-related psychiatric symptoms (nightmare, abnormal dreams, sleep terror, etc.), emotional and perceptual abnormalities (hallucination, depression, agitation), physiological and behavioral responses (palpitations, dry mouth, energy increased, etc.), suicide risk (suicidal ideation, intentional overdose), and other special concern AEs (tachyphrenia, sleep-related eating disorder, hypersensitivity). CONCLUSION: Although some new potential AEs have been identified, these findings need further verification in broader datasets and long-term studies due to limitations in data sources and analysis methods. Future research should comprehensively assess the safety and effectiveness of daridorexant, providing more accurate guidance for medical professionals in the treatment of insomnia.

ERBB2 mutations define a subgroup of endometrial carcinomas associated with high tumor mutational burden and the microsatellite instability-high (MSI-H) molecular subtype.

Anti-HER2 therapy is indicated for erb-b2 receptor tyrosine kinase 2 (ERBB2)-amplified/overexpressing endometrial carcinoma (EC). Mutations constitute another mode of ERBB2 activation, but only rare ERBB2-mutated ECs have been reported. We sought to characterize the clinicopathologic and genetic features of ERBB2-mutated EC. From an institutional cohort of 2638 ECs subjected to clinical tumor-normal panel sequencing, 69 (2.6%) with pathogenic ERBB2 mutation(s) were identified, of which 11 were also ERBB2-amplified. The most frequent ERBB2 hotspot mutations were V842I (38%) and R678Q (25%). ERBB2 mutations were clonal in 87% of evaluable cases. Immunohistochemistry revealed low HER2 protein expression in most ERBB2-mutated ECs (0/1+ in 66%, 2+ in 27%); all 3+ tumors (7.3%) were also ERBB2-amplified. Compared to ERBB2-wildtype ECs (with or without ERBB2 amplification), ERBB2-mutated/non-amplified ECs were enriched for the microsatellite instability-high (MSI-H) and, to a lesser extent, DNA polymerase epsilon, catalytic subunit (POLE) molecular subtypes, and associated with high tumor mutational burden and low chromosomal instability. Survival outcomes were similar between patients with ERBB2-mutated/non-amplified versus wildtype EC, whereas ERBB2 amplification was associated with worse prognosis on univariate, but not multivariate, analyses. In conclusion, ERBB2 mutation defines a rare subgroup of ECs that is pathogenically distinct from ERBB2-wildtype and ERBB2-amplified ECs.

Extraocular muscle volume on time-of-flight magnetic resonance angiography in patients with myasthenia gravis.

INTRODUCTION/AIMS: Despite being a prominent feature of myasthenia gravis (MG), extraocular muscle (EOM) has received little attention in clinical research. The aim of this study was to examine EOM volume in patients with MG and controls using time-of-flight magnetic resonance angiography (TOF-MRA). METHODS: EOM volumes (overall and individual rectus muscles) were calculated using TOF-MRA images and compared between MG patients (including subgroups) and controls. The correlation between EOM volume and disease duration was examined. Predictive equations for the selected parameters were developed using multiple linear regression analysis. RESULTS: EOM volume was lower in MG patients than controls, especially in MG patients with ophthalmoparesis (MG-O). MG-O exhibited a moderate negative correlation between EOM volume and disease duration. Multiple linear regression showed that disease duration and EOM status (ophthalmoparesis or not) account for 48.4% of EOM volume. DISCUSSION: Patients with MG show atrophy of the EOMs, especially those with ophthalmoparesis and long disease duration.

Folate receptor alpha expression in low-grade serous ovarian cancer: Exploring new therapeutic possibilities.

OBJECTIVE: Mirvetuximab soravtansine may be a potentially effective therapeutic option for ovarian low-grade serous carcinoma (LGSC), but the prevalence of folate receptor alpha (FRα) overexpression in this tumor type is unknown. We sought to characterize FRα expression in LGSC and its association with clinical and molecular features. METHODS: FRα immunohistochemistry was performed on a tissue microarray comprised of 89 LGSCs and 42 ovarian serous borderline tumors (SBTs). Clinical tumor-normal panel-based sequencing was performed on 78 LGSCs. Associations between FRα-high status and clinicopathologic characteristics and survival outcomes were examined. RESULTS: Of 89 LGSCs, 36 (40%) were FRα-high (≥75% of viable tumor cells exhibiting moderate-to-strong membranous expression). Of 9 patients with LGSC and samples from different timepoints, 4 (44%) had discordant results, with conversion from FRα-negative to FRα-high in 3 (33%) cases. There was no association between FRα-high status with age, race, or progression-free/overall survival. A MAPK pathway genetic alteration, most commonly involving KRAS (n = 23), was present in 45 (58%) LGSCs. Those lacking MAPK pathway alterations were more likely to be FRα-high compared to MAPK-altered LGSCs (61% vs 20%, p < 0.001). In SBTs, FRα-high expression was associated with high-risk (micropapillary) histology and/or subsequent LGSC recurrence compared to conventional SBTs without malignant recurrence (53% vs 9%, p = 0.008). CONCLUSIONS: Future studies of FRα-directed therapy in patients with LGSC are warranted. Discordant FRα status at recurrence suggests potential benefit for retesting. A biomarker-driven approach to direct treatment selection in LGSC is recommended. As high FRα expression is more common amongst tumors lacking MAPK pathway genetic alterations, FRα testing to determine eligibility for mirvetuximab soravtansine therapy is particularly recommended for this subgroup.

Controlled NiOx Defect Engineering to Harnessing Redox Reactions in Perovskite Photovoltaic Cells via Atomic Layer Deposition.

Albeit the undesirable attributes of NiOx, such as low conductivity, unmanageable defects, and redox reactions occurring at the perovskite/NiOx interface, which impede the progress in inverted perovskite solar cells (i-PSCs), it is the most favorable choice of technology for industrialization of PSCs. In this study, we propose a novel Ni vacancy defect modulate approach to leverage the conformal growth and surface self-limiting reaction characteristics of the atomic layer deposition (ALD)-fabricated NiOx by varying the O2 plasma injection time (tOE) to induce self-doping. Consequently, NiOx thin films with enhanced conductivity, an appropriate Ni3+/Ni2+ ratio, stable surface states, and ultrathinness are realized as hole-transporting layers (HTLs) in p-i-n PSCs. As a result of these improvements, ALD-NiOx-based devices exhibit the highest power conversion efficiency (PCE) of 19.86% and a fill factor (FF) of 81.86%. Notably, the optimal interfacial defects effectively suppressed the severe reaction between the perovskite and NiOx. This suppression is evidenced by the lowest decay rate observed in a harsh environment, lasting for 500 consecutive hours. The proposed approach introduces the possibility of a hierarchical distribution of defects and offers feasibility for the fabrication of large-area, uniform, and high-quality films.

GOLPH3 knockdown alleviates the inflammation and apoptosis in lipopolysaccharide-induced acute lung injury by inhibiting Golgi stress mediated autophagy.

Pneumonia, an acute inflammatory lesion of the lung, is the leading cause of death in children aged < 5 years. We aimed to study the function and mechanism of Golgi phosphoprotein 3 (GOLPH3) in infantile pneumonia. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and injury of MLE-12 cells were used as the pneumonia model in vitro. After GOLPH3 was knocked down, the histopathological changes of lung tissues were assessed by hematoxylin-eosin (H&E) staining. The Wet/Dry ratio of lung tissues was calculated. The enzyme-linked immunosorbent assay (ELISA) method was used to detecte the contents of inflammatory factors in bronchoalveolar lavage fluid (BALF). The damaged DNA in apoptotic cells in lung tissues was tested by Terminal deoxynucleotidyl transferase-mediated dUTP Nick end labeling (TUNEL) staining. Immunofluorescence staining analyzed LC3II and Golgi matrix protein 130 (GM130) expression in lung tissues and MLE-12 cells. The apoptosis of MLE-12 cells was measured by flow cytometry analysis. Additionally, the expression of proteins related to apoptosis, autophagy and Golgi stress was examined with immunoblotting. Results indicated that GOLPH3 knockdown alleviated lung tissue pathological changes in LPS-triggered ALI mice. LPS-induced inflammation and apoptosis in lung tissues and MLE-12 cells were remarkably alleviated by GOLPH3 deficiency. Besides, GOLPH3 depletion suppressed autophagy and Golgi stress in lung tissues and MLE-12 cells challenged with LPS. Moreover, Rapamycin (Rap), an autophagy inhibitor, counteracted inflammation and apoptosis inhibited by GOLPH3 silencing in LPS-induced MLE-12 cells. Furthermore, brefeldin A (BFA) pretreatment apparently abrogated the inhibitory effect of GOLPH3 knockdown on autophagy in MLE-12 cells exposed to LPS. To be concluded, GOLPH3 knockdown exerted lung protective effect against LPS-triggered inflammation and apoptosis by inhibiting Golgi stress mediated autophagy.

NagZ modulates the virulence of E. cloacae by acting through the gene of unknown function, ECL_03795.

ß-N-acetylglucosaminidase (NagZ), a cytosolic glucosaminidase, plays a pivotal role in peptidoglycan recycling. Previous research demonstrated that NagZ knockout significantly eradicated AmpC-dependent ß-lactam resistance in Enterobacter cloacae. However, NagZ's role in the virulence of E. cloacae remains unclear. Our study, incorporating data on mouse and Galleria mellonella larval mortality rates, inflammation markers, and histopathological examinations, revealed a substantial reduction in the virulence of E. cloacae following NagZ knockout. Transcriptome sequencing uncovered differential gene expression between NagZ knockout and wild-type strains, particularly in nucleotide metabolism pathways. Further investigation demonstrated that NagZ deletion led to a significant increase in cyclic diguanosine monophosphate (c-di-GMP) levels. Additionally, transcriptome sequencing and RT-qPCR confirmed significant differences in the expression of ECL_03795, a gene with an unknown function but speculated to be involved in c-di-GMP metabolism due to its EAL domain known for phosphodiesterase activity. Interestingly, in ECL_03795 knockout strains, a notable reduction in the virulence was observed, and virulence was rescued upon complementation with ECL_03795. Consequently, our study suggests that NagZ's function on virulence is partially mediated through the ECL_03795→c-di-GMP pathway, providing insight into the development of novel therapies and strongly supporting the interest in creating highly efficient NagZ inhibitors.

Flexible, Wearable Wireless-Charging Power System Incorporating Piezo-Ultrasonic Arrays and MXene-Based Solid-State Supercapacitors.

With the continuous development of wearable electronics, higher requirements are put forward for flexible, detachable, stable output, and long service life power modules. Given the limited capacity of energy storage devices, the integration of energy capture and storage is a viable approach. Here, we present a flexible, wearable, wireless-charging power system that integrates a piezoelectric ultrasonic array harvester (PUAH) with MXene-based solid-state supercapacitors (MSSSs) in a soft wristband format for sustainable applications. The MSSS as the energy storage module is developed by using Ti3C2Tx nanosheet-loaded inserted finger-like carbon cloth skeletons as electrodes and poly(vinyl alcohol)/H3PO4 gel as electrolytes, with high energy density (58.74 Wh kg-1) and long cycle life (99.37%, 10,000 cycles). A two-dimensional stretchable piezoelectric array as a wireless-charging module hybridizes high-performance 1-3 composite units with serpentine electrodes, which allows wireless power via ultrasonic waves, with a maximum power density of 1.56 W cm-2 and an output voltage of 20.75 V. The overall PUAH-MSSS wireless energy supply system is 2 mm thick and offers excellent energy conversion/storage performance, cyclic stability, and mechanical flexibility. The results of this project will lay the foundation for the development of next-generation wearable electronics.

Synergistic enhancement of anthocyanin stability and techno-functionality of colored wheat during the steamed bread processing by selectively hydrolyzed soy protein.

To improve the stability of anthocyanins and techno-functionality of purple and blue wheat, the selectively hydrolyzed soy protein (reduced glycinin, RG) and ß-conglycinin (7S) were prepared and their enhanced effects were comparatively investigated. The anthocyanins in purple wheat showed higher stability compared to that of the blue wheat during breadmaking. The cyanidin-3-O-glucoside and cyanidin-3-O-rutincoside in purple wheat and delphinidin-3-O-rutinoside and delphinidin-3-O-glucoside in blue wheat were better preserved by RG. Addition of RG and 7S enhanced the quality of steamed bread made from colored and common wheat, with RG exhibited a more prominent effect. RG and 7S suppressed the gelatinization of starch and improved the thermal stability. Both RG and 7S promoted the unfolding process of gluten proteins and facilitated the subsequent crosslinking of glutenins and gliadins by disulfide bonds. Polymerization of α- and γ-gliadin into glutenin were more evidently promoted by RG, which contributed to the improved steamed bread quality.