Therapeutic sleep deprivation for major depressive disorder: A randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Rim 18F-fluorodeoxyglucose uptake of hepatic cavernous hemangioma on positron emission tomography/computed tomography: A case report.

BACKGROUND: Peripheral FDG accumulation in a hepatic hemangioma presenting in a patient with prolonged fever is rare. Therefore, clinicians should pay close attention to patients with hepatic mass. CASE SUMMARY: A 54-year-old woman with a 4-wk history of daily fevers was admitted to our hospital. A whole body 18F-Fluordesoxyglucose (PET-FDG) positron emission tomography/computed tomography (PET/CT) was performed to elucidate the source of the fever. However, whole body 18F-FDG PET/CT raised the suspicion of a malignant lesion because of peripheral FDG accumulation (SUVmax 3.5 g/mL) higher than that of the normal liver parenchyma (SUVmax 1.6 g/mL) surrounding a hypoactive area, and no other abnormalities were showed. Subsequently, the patient underwent liver mass resection. Histopathology showed a hepatic cavernous hemangioma with fatty infiltration around the lesion. The fever disappeared four days after surgery and the patient did not present any complications during follow-up. CONCLUSION: Fatty infiltration in the peripheral parts of hepatic cavernous hemangioma may lead to subacute inflammation which further activate the Kupffer cells. This may cause prolonged fever and peripheral rim FDG accumulation on PET/CT.

Red cell distribution width to total serum calcium ratio and in-hospital mortality risk in patients with acute ischemic stroke: A MIMIC-IV retrospective analysis.

We investigated the relationship among red cell distribution width (RDW), to total serum calcium (TSC) ratio (RCR), and in-hospital mortality in patients with acute ischemic stroke (AIS). This study was a retrospective analysis. The data of 2700 AIS patients was retrospectively analyzed from the Medical Information Mart for Intensive Care database (version IV). The main outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether RCR was independently associated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves for RCR. Subgroup analyses were performed to measure the mortality across various subgroups. The area under curve (AUC) of receiver operating characteristic curve (ROC) was calculated to ascertain the quality of RCR as a predictor of in-hospital mortality in patients with AIS. In the multivariate analysis, statistically significant differences were identified in age, ethnicity, length of ICU stay, mechanical ventilation, sequential organ failure assessment (SOFA) score, RDW, hemoglobin, RCR, whether taking anticoagulants, hyperlipidemia, and atrial fibrillation (P < .05). A threshold inflection point value of 1.83 was obtained through a two-piecewise regression model. There was a non-linear relationship between RCR and hospital mortality in patients with AIS. The hazard ratio (HR) and the 95% confidence intervals (CI) on the right and left of the inflection point were 0.93 (0.57-1.51; P = .7660) and 2.96 (1.37-6.42; P = .0060), respectively. The Kaplan-Meier curve indicated that survival rates were higher when RCR was ≤ 1.83 and lower when RDW was > 1.83 after adjustment for age, gender, BMI, ethnicity. The area under curve (AUC) of RCR was 0.715. A higher RCR was associated with an increased risk of in-hospital mortality in patients with AIS.

Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), a novel ALPPS procedure for the treatment of hepatocellular carcinoma with severe fibrosis: Retrospective clinical cohort study.

BACKGROUND: Associating liver partition with portal vein ligation for staged liver resection (ALPPS) has been used in the treatment of patients with advanced or massive liver cancer without sufficient future liver remnant, but concerns remain regarding tumor outcomes and surgical safety. This study aims to evaluate the efficacy and safety of a new procedure, Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), in the treatment of HCC patients especially with severe fibrosis. METHODS: This retrospective study analyzed 8 patients who underwent HARO-ALPPS for HCC and compared their outcomes with 64 patients who underwent conventional ALPPS. The primary outcomes assessed were liver regeneration ability (measured by relative and absolute kinetic growth rates), postoperative complications, and mortality. The secondary outcomes included overall survival and disease-free survival. RESULTS: HARO-ALPPS significantly restricted the blood supply of the hepatic artery. One week after surgery, the blood flow of the right hepatic artery dropped to 62.1%. At the same time, HARO-ALPPS shows superior liver regeneration ability, which is particularly prominent in the background of liver fibrosis. No serious complications occurred after HARO-ALPPS. The overall survival rate of HARO-ALPPS was 75%, which was higher than that of ALPPS (64%, P=0.816). CONCLUSION: Compared to conventional ALPPS, HARO-ALPPS exhibits a better liver regeneration ability, and favorable long-term outcomes. Further prospective studies are needed to validate these findings and evaluate the long-term oncologic outcomes of this novel procedure.

Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study.

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.

Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

From leaf to multiscale models of photosynthesis: applications and challenges for crop improvement.

To keep up with the growth of human population and to circumvent deleterious effects of global climate change, it is essential to enhance crop yield to achieve higher production. Here we review mathematical models of oxygenic photosynthesis that are extensively used, and discuss in depth a subset that accounts for diverse approaches providing solutions to our objective. These include models (1) to study different ways to enhance photosynthesis, such as fine-tuning antenna size, photoprotection and electron transport; (2) to bioengineer carbon metabolism; and (3) to evaluate the interactions between the process of photosynthesis and the seasonal crop dynamics, or those that have included statistical whole-genome prediction methods to quantify the impact of photosynthesis traits on the improvement of crop yield. We conclude by emphasizing that the results obtained in these studies clearly demonstrate that mathematical modelling is a key tool to examine different approaches to improve photosynthesis for better productivity, while effective multiscale crop models, especially those that also include remote sensing data, are indispensable to verify different strategies to obtain maximized crop yields.

Berlin Green with tunable iron content as ultra-high rate host for efficient aqueous ammonium ion storage.

Prussian blue analogues (PBAs) are regarded as promising cathode materials for ammonium-ion batteries (AIBs) because of their low cost and superb theoretical capacity. However, its inherently poor conductivity and structural collapse can significantly limit the enhancement of rate property and cycling stability. In this work, Berlin Green (BG) electrode materials with similar wool-like clusters were constructed by direct precipitation method to accelerate the kinetic, which realizes outstanding cycling stability. Berlin Green with the appropriate amount of iron (BG-2) has a fast ion transport channel, enhanced structure stability, highly reversible insertion/extraction of NH4+, and fine electrochemical reaction activity. Benefiting from the unique architecture and component, the BG-2 electrode shows an excellent rate performance with a discharge/charge specific capacity of 60.1/59.3 mAh g-1 at 5 A g-1. Even at 5 A g-1, BG-2 exhibits remarkable cycling stability with an initial discharge capacity of 59.5 mAh g-1 and a capacity retention rate of approximately 76% after 30,000 cycles. The BG-2 reveals exceedingly good electrochemical reversibility during the process of NH4+ (de)insertion. BG materials indicate huge potential as a cathode material for the next generation of high-performance aqueous batteries.

[Air Microbial Contamination and Risk of Respiratory Exposure of Workers in Chicken Farms].

Animal farms are important sources of microbial contamination in the air environment. However, there are few reports on the time-regularity characteristics of airborne microbial contamination in farms. In the context of this situation, a study was conducted for more than 80 weeks using 16S rRNA gene amplicon sequencing to characterize the bacterial distribution and respiratory exposure in the farm air and fecal environment, respectively, taking a layer farm as an example. The results showed that 16S rRNA concentrations in air and manure samples ranged from 6.08×105-4.90×106 copies·m-3 and 4.27×108-1.15×1010 copies·g-1, respectively. The mean values of airborne bacterial concentrations were significantly higher in winter than in summer, whereas the biodiversity showed the opposite trend. The dominant bacterial phylum in both air and manure in the layer farm was Firmicutes. During the investigated time, the top three dominant genera in the air were relatively stable, in the order of Lactobacillus, Bacteroides, and Faecalibacterium, whereas the dominant genera in feces fluctuated with the increase in breeding time. The correlation between the community structure of bacteria and pathogenic bacteria in both air and manure was not significant, but the concentrations of both target microorganisms in different media were significantly correlated. The bioaerosolization index of bacteria in manure showed an increasing trend with increasing breeding time, whereas the opposite trend was observed for pathogenic bacteria. In this case, [Ruminococcus]_torques_group, Bacteroides, and Faecalibacterium were the top three pathogenic genera that were the most prone to aerosolization. There were seasonal differences in bacterial respiratory exposures of chicken farm workers, with mean intake values of 2.54×107 copies·d-1 and 2.87×105 copies·d-1 for bacteria and pathogenic bacteria, respectively. The results of this study will provide a scientific basis for systematically assessing the contamination characteristics and potential health risks of airborne microorganisms on farms and for developing corresponding industry standards for occupational exposure and prevention and control measures.

Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway.

BACKGROUND: In this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5'-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PURPOSE: The aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. STUDY DESIGN: HUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. METHODS: In type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. RESULTS: We first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. CONCLUSIONS: The main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Glial fibrillary acidic protein astrocytopathy presented as meningitis: A case report.

Introduction: Glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune neurological disorder and is diagnosed by GFAP-IgG in cerebrospinal fluid (CSF) measurement. Case report: Herein, we described a 10-year-old boy with abnormal neurological symptoms and signs. GFAP-IgG was detected in CSF using cell-based assay (CBA), and his CSF showed an increase in lymphocytes, a slight decrease in glucose and an increase in protein level in the early stage. The cranial MRI showed multiple strips of T2-FLAIR hyperintense signal changes on the surface of medulla oblongata, pons, and gyrus in bilateral cerebral hemispheres. He was treated with immunoglobulin (IVIG) and high-dose methylprednisolone pulse treatment, and his clinical presentations gradually improved. Conclusion: We highlight that patients with normal inflammatory markers in peripheral blood have obvious meningitis-like symptoms, and clinicians need to consider GFAP astrocytopathy. The early diagnosis and treatment of GFAP astrocytopathy are important for improving the prognosis.

Left Hepatectomy Combined with Right Hepatic Artery Resection and Reconstruction for Hilar Cholangiocarcinoma.

BACKGROUND: Hepatectomy combined with hepatic artery reconstruction in the operation for hilar cholangiocarcinoma (Klatskin tumor) is a challenging procedure. We present a video of left hepatectomy combined with right hepatic artery reconstruction for hilar cholangiocarcinoma. PATIENT AND METHODS: The patient was a 60-year-old male who presented with obstructive jaundice. The imaging examination showed that the confluence of left and right hepatic ducts and the wall of common hepatic duct were thickened, the local lumen was narrowed, the intrahepatic bile duct was dilated, and the right hepatic artery was invaded by tumors nearly 2.3 centimeters. Left hepatectomy with total caudate lobectomy, resection with reconstruction of right hepatic artery, hilar lymphadenectomy, and Roux-en-Y hepaticojejunostomy were performed. RESULTS: The operation time was 345 min, and the amount of bleeding was about 400 ml. There was no blood transfusion. The pathology showed poorly differentiated adenocarcinoma, with negative margins of common bile duct and right hepatic duct, and negative results of all lymph nodes. The patient's recovery was uneventful and he was discharged on postoperative day 14. The patient was disease free at 12-month follow-up evaluation. CONCLUSIONS: Hepatic artery resection and reconstruction procedure is safe and feasible for hilar cholangiocarcinoma in a highly tertiary hepatobiliary center.

MCPNET: Development of an interpretable deep learning model based on multiple conformations of the compound for predicting developmental toxicity.

The development of deep learning models for predicting toxicological endpoints has shown great promise, but one of the challenges in the field is the accuracy and interpretability of these models. The bioactive conformation of a compound plays a critical role for it to bind in the target. It is a big issue to figure out the bioactive conformation in deep learning without the co-crystal structure or highly precise molecular simulations. In this study, we developed a deep learning framework of Multi-Conformation Point Network (MCPNET) to construct classification and regression models, respectively, based on electrostatic potential distributions on vdW surfaces around multiple conformations of the compound using a dataset of compounds with developmental toxicity in zebrafish embryo. MCPNET applied 3D multi-conformational surface point cloud to extract the molecular features for model training, which may be critical for capturing the structural diversity of compounds. The models achieved an accuracy of 85 % on the classification task and R2 of 0.66 on the regression task, outperforming traditional machine learning models and other deep learning models. The key feature of our model is its interpretability with the component visualization to identify the factors contributing to the prediction and to understand the compound action mechanism. MCPNET may predict the conformation quietly close to the bioactive conformation of a compound by attention-based multi-conformation pooling mechanism. Our results demonstrated the potential of deep learning based on 3D molecular representations in accurately predicting developmental toxicity. The source code is publicly available at https://github.com/Superlit-CC/MCPNET.

Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection.

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.

Key candidate genes for male sterility in peppers unveiled via transcriptomic and proteomic analyses.

This study aimed to enhance the use of male sterility in pepper to select superior hybrid generations. Transcriptomic and proteomic analyses of fertile line 1933A and nucleic male sterility line 1933B of Capsicum annuum L. were performed to identify male sterility-related proteins and genes. The phylogenetic tree, physical and chemical characteristics, gene structure characteristics, collinearity and expression characteristics of candidate genes were analyzed. The study identified 2,357 differentially expressed genes, of which 1,145 and 229 were enriched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, respectively. A total of 7,628 quantifiable proteins were identified and 29 important proteins and genes were identified. It is worth noting that the existence of CaPRX genes has been found in both proteomics and transcriptomics, and 3 CaPRX genes have been identified through association analysis. A total of 66 CaPRX genes have been identified at the genome level, which are divided into 13 subfamilies, all containing typical CaPRX gene conformal domains. It is unevenly distributed across 12 chromosomes (including the virtual chromosome Chr00). Salt stress and co-expression analysis show that male sterility genes are expressed to varying degrees, and multiple transcription factors are co-expressed with CaPRXs, suggesting that they are involved in the induction of pepper salt stress. The study findings provide a theoretical foundation for genetic breeding by identifying genes, metabolic pathways, and molecular mechanisms involved in male sterility in pepper.

Dynamic Analysis of Chlorophyll a Fluorescence in Response to Time-Variant Excitations during Strong Actinic Illumination and Application in Probing Plant Water Loss.

Magnitude measurement of chlorophyll a fluorescence (ChlF) involves challenges, and dynamic responses to variable excitations may offer an alternative. In this research, ChlF was measured during strong actinic light by using a pseudo-random binary sequence as a time-variant multiple-frequency illumination excitation. The responses were observed in the time domain but were primarily analyzed in the frequency domain in terms of amplitude gain variations. The excitation amplitude was varied, and moisture loss was used to induce changes in the plant samples for further analysis. The results show that when nonphotochemical quenching (NPQ) activities start, the amplitude of ChlF responses vary, making the ChlF responses to illumination excitations nonlinear and nonstationary. NPQ influences the ChlF responses in low frequencies, most notably below 0.03 rad/s. The low-frequency gain is linearly correlated with NPQ and can thus be used as a reference to compensate for the variations in ChlF measurements. The high-frequency amplitude gain showed a stronger correlation with moisture loss after correction with the low-frequency gain. This work demonstrates the usefulness of dynamic characteristics in broadening the applications of ChlF measurements in plant analysis and offers a way to mitigate variabilities in ChlF measurements during strong actinic illumination.