Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma.

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

Benefits of napping habits in healthy adults: Maintaining alerting performance and cortisol levels change within 90 min of habitual napping time.

BACKGROUND: Napping is garnering increased attention as a strategy for adults to sustain alertness and alleviate stress in contemporary society. The nuances of napping habits are emerging as an independent factor influencing the extent of individual benefits. This study aimed to demonstrate the long-term benefits of napping and explore the impact of napping habits on individual alertness, as well as whether this effect was correlated with cortisol levels. METHODS: The study involved 80 healthy adults categorized into two groups based on self-reported napping habits: habitual nappers (n = 49) and non-habitual nappers (n = 31). Karolinska Sleepiness Scale (KSS), psychomotor vigilance task (PVT), and saliva collection were performed every 30 min within 90 min in the absence of napping during the afternoon dip. The measurements were analyzed using repeated measures ANOVA and Pearson correlation analyses. RESULTS: There was an interaction between groups and time in reaction speed and lapse number of PVT and cortisol (all p < 0.05). Post hoc analysis found that habitual nappers maintained higher objective alertness and experienced more significant increases in cortisol over time (all p < 0.05). The cortisol levels at sleepiness time were negatively associated with the slowest 10 % reaction speed of PVT in non-habitual nappers (r = -0.409, p = 0.022). CONCLUSION: Under the premise of mitigating the impacts of acute nap deprivation on sleep homeostasis and rhythm, napping habits emerge as a potential factor influencing the ability of individuals to sustain heightened alertness.

A real­world pharmacovigilance study of FDA adverse event reporting system events for daratumumab.

BACKGROUND: Daratumumab, a first-in-class humanized IgG1κ monoclonal antibody that targets the CD38 epitope, has been approved for treatment of multiple myeloma by FDA. The current study was to evaluate daratumumab-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of daratumumab-associated AEs. RESULTS: Out of 10,378,816 reports collected from the FAERS database, 8727 reports of daratumumab-associated AEs were identified. A total of 183 significant disproportionality preferred terms (PTs) were retained. Unexpected significant AEs such as meningitis aseptic, leukoencephalopathy, tumor lysis syndrome, disseminated intravascular coagulation, hyperviscosity syndrome, sudden hearing loss, ileus and diverticular perforation were also detected. The median onset time of daratumumab-related AEs was 11 days (interquartile range [IQR] 0-76 days), and most of the cases occurred within 30 days. CONCLUSION: Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship.

[A Growth Prediction Model of Pulmonary Ground-Glass Nodules Based on Clinical Visualization Parameters].

Objective To establish a model for predicting the growth of pulmonary ground-glass nodules (GGN) based on the clinical visualization parameters extracted by the 3D reconstruction technique and to verify the prediction performance of the model. Methods A retrospective analysis was carried out for 354 cases of pulmonary GGN followed up regularly in the outpatient of pulmonary nodules in Zhoushan Hospital of Zhejiang Province from March 2015 to December 2022.The semi-automatic segmentation method of 3D Slicer was employed to extract the quantitative imaging features of nodules.According to the follow-up results,the nodules were classified into a resting group and a growing group.Furthermore,the nodules were classified into a training set and a test set by the simple random method at a ratio of 7∶3.Clinical and imaging parameters were used to establish a prediction model,and the prediction performance of the model was tested on the validation set. Results A total of 119 males and 235 females were included,with a median age of 55.0 (47.0,63.0) years and the mean follow-up of (48.4±16.3) months.There were 247 cases in the training set and 107 cases in the test set.The binary Logistic regression analysis showed that age (95%CI=1.010-1.092,P=0.015) and mass (95%CI=1.002-1.067,P=0.035) were independent predictors of nodular growth.The mass (M) of nodules was calculated according to the formula M=V×(CTmean+1000)×0.001 (where V is the volume,V=3/4πR3,R:radius).Therefore,the logit prediction model was established as ln[P/(1-P)]=-1.300+0.043×age+0.257×two-dimensional diameter+0.007×CTmean.The Hosmer-Lemeshow goodness of fit test was performed to test the fitting degree of the model for the measured data in the validation set (χ2=4.515,P=0.808).The check plot was established for the prediction model,which showed the area under receiver-operating characteristic curve being 0.702. Conclusions The results of this study indicate that patient age and nodule mass are independent risk factors for promoting the growth of pulmonary GGN.A model for predicting the growth possibility of GGN is established and evaluated,which provides a basis for the formulation of GGN management strategies.

Clinical performance of metagenomic next-generation sequencing for diagnosis of pulmonary Aspergillus infection and colonization.

Background: Investigations assessing the value of metagenomic next-generation sequencing (mNGS) for distinguish Aspergillus infection from colonization are currently insufficient. Methods: The performance of mNGS in distinguishing Aspergillus infection from colonization, along with the differences in patients' characteristics, antibiotic adjustment, and lung microbiota, were analyzed. Results: The abundance of Aspergillus significantly differed between patients with Aspergillus infection (n=36) and colonization (n=32) (P < 0.0001). Receiver operating characteristic (ROC) curve result for bronchoalveolar lavage fluid (BALF) mNGS indicated an area under the curve of 0.894 (95%CI: 0.811-0.976), with an optimal threshold value of 23 for discriminating between Aspergillus infection and colonization. The infection group exhibited a higher proportion of antibiotic adjustments in comparison to the colonization group (50% vs. 12.5%, P = 0.001), with antibiotic escalation being more dominant. Age, length of hospital stay, hemoglobin, cough and chest distress were significantly positively correlated with Aspergillus infection. The abundance of A. fumigatus and Epstein-Barr virus (EBV) significantly increased in the infection group, whereas the colonization group exhibited higher abundance of A. niger. Conclusion: BALF mNGS is a valuable tool for differentiating between colonization and infection of Aspergillus. Variations in patients' age, length of hospital stay, hemoglobin, cough and chest distress are observable between patients with Aspergillus infection and colonization.

Identification of immune subtypes associated with neutrophils in tuberculosis infection based on weighted gene co-expression network analysis.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is a major global health concern. Neutrophils play a significant role in TB infection and patient outcomes. This study aimed to identify gene modules associated with neutrophil infiltration in TB samples using WGCNA. Gene ontology and enrichment analyses were performed, and a random forest model was constructed to identify differentially expressed genes. K-means clustering was used to classify samples into subtypes, and immune-related scores, PD-L1 expression, HLA expression, and gene enrichment analysis were evaluated. The blue module showed significant correlation with neutrophils and enrichment in immune-related processes. The model exhibited good classification performance, and subtype 1 demonstrated higher immune-related scores, PD-L1 expression, HLA class I molecule expression, and immune-related pathway enrichment. These findings enhance our understanding of TB pathogenesis and provide potential targets for diagnosis and treatment strategies.

Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis.

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP inhibitor, we successfully induce macrophage re-polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1-YAP signalling axis in macrophage mechanosensing and stiffness-mediated macrophage polarisation and provides cues for the design of immuno-modulatory biomaterials that can regulate the macrophage phenotype.

A Scalable and Robust Personal Health Management Textile with Multiple Desired Thermal Functions and Electromagnetic Shielding.

The development of functional textiles combining conventional apparel with advanced technologies for personal health management (PHM) has garnered widespread attention. However, the current PHM textiles often achieve multifunctionality by stacking functional modules, leading to poor durability and scalability. Herein, a scalable and robust PHM textile is designed by integrating electrical, radiative, and solar heating, electromagnetic interference (EMI) shielding, and piezoresistive sensing performance onto cotton fabric. This is achieved through an uncomplicated screen-printing process using silver paste. The conductivity of the PHM textile is ≈1.6  ×  104 S m-1, ensuring an electric heating temperature of ≈134 °C with a low voltage of 1.7 V, as well as an EMI shielding effectiveness of ≈56 dB, and human motion monitoring performance. Surprisingly, the radiative/solar heating capability of the PHM textile surpasses that of traditional warm leather. Even after undergoing rigorous physical and chemical treatments, the PHM textile maintains terrific durability. Additionally, the PHM textile possesses maneuverable scalability and comfortable wearability. This innovative work opens up new avenues for the strategic design of PHM textiles and provides an advantageous guarantee of mass production.

Ultralight Flexible Collagen Fiber Based Aerogels Derived from Leather Solid Waste for High Electromagnetic Interference Shielding.

Designing and developing high-performance shielding materials against electromagnetic interference is of utmost importance due to the rapid advancement of wireless telecommunication technologies. Such materials hold both fundamental and technological significance. A three-stage process is presented for creating ultralight, flexible aerogels from biomass to shield against electromagnetic interference. Collagen fibers sourced from leather solid waste are used for: (i) freeze-drying preparation of collagen fibers/poly(vinyl alcohol) (PVA) aerogels, (ii) adsorption of silver nanowires (AgNWs) onto collagen fiber/PVA aerogels, and (iii) Hydrophobic modification of collagen fiber/PVA/AgNWs aerogels with 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane (POTS). Scanning electron microscopy studies reveal that an interweaving of AgNWs and collagen fiber/PVA porous network has formed a conductive network, exhibiting an electrical conductivity of 103 S·m-1. The electromagnetic interference shielding effectiveness reached more than 62 dB, while the density was merely 5.8 mg/cm3. The collagen fiber/PVA/AgNWs/POTS aerogel displayed an even better electromagnetic shielding efficiency of 73 dB and water contact angle of 147°. The study results emphasize the distinctive capacity of leather solid waste to generate cost-effective, ecofriendly, and highly efficient electromagnetic interference shielding materials.

Reaction sites of pyrimidine bases and nucleosides during chlorination: A computational study.

As important components of soluble microbial products in water, nucleobases have attracted much attention due to the high toxicity of their direct aromatic halogenated disinfection by-products (AH-DBPs) during chlorination. However, multiple halogenation sites of AH-DBPs pose challenges to identify them. In this study, reaction sites of pyrimidine bases and nucleosides during chlorination were investigated by quantum chemical computational method. The results indicate that the anion salt forms play key roles in chlorination of uracil, thymine, and their nucleosides, while neutral forms make predominant contributions to cytosine and cytidine. In view of both kinetics and thermodynamics, C5 is the most reactive site for uracil and thymine, N3/C5 and N3 for respective uridine and thymidine, N1/C5/N4 and N4 for respective cytosine and cytidine, whose estimated apparent rate constants kobs-est of ∼103, 103/102, 106/102/104, and 103 M-1 s-1, respectively, in consistent with the known experimental results. C6 in all pyrimidine compounds is hardly attacked by Cl+ in HOCl ascribed to its positive charge, but readily attacked by OH‾ in hydrolysis and the N1=C6 bond was found to possess the highest reactivity in hydrolysis among all double bonds. In addition, the structure-kinetic reactivity relationship study reveals a relatively strong correlation between lgkobs-est and APT charge in all pyrimidine compounds rather than FED2 (HOMO). The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination.

Effectiveness analysis of three-drug combination therapies for refractory focal epilepsy.

Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann-Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini-Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n â€‹= â€‹95). At the last clinical visit, 14.9% (n â€‹= â€‹48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17-0.85; adjusted P â€‹< â€‹0.001) and 0.63 (IQR, 0.21-1.04; adjusted P â€‹< â€‹0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR â€‹= â€‹0.67; adjusted P â€‹= â€‹0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.

Identification of reaction sites and chlorinated products of purine bases and nucleosides during chlorination: a computational study.

Hypochlorous acid (HOCl) released from activated leukocytes plays a significant role in the human immune system, but is also implicated in numerous diseases due to its inappropriate production. Chlorinated nucleobases induce genetic changes that potentially enable and stimulate carcinogenesis, and thus have attracted considerable attention. However, their multiple halogenation sites pose challenges to identify them. As a good complement to experiments, quantum chemical computation was used to uncover chlorination sites and chlorinated products in this study. The results indicate that anion salt forms of all purine compounds play significant roles in chlorination except for adenosine. The kinetic reactivity order of all reaction sites in terms of the estimated apparent rate constant kobs-est (in M-1 s-1) is heterocyclic NH/N (102-107) > exocyclic NH2 (10-2-10) > heterocyclic C8 (10-5-10-1), but the order is reversed for thermodynamics. Combining kinetics and thermodynamics, the numerical simulation results show that N9 is the most reactive site for purine bases to form the main initial chlorinated product, while for purine nucleosides N1 and exocyclic N2/N6 are the most reactive sites to produce the main products controlled by kinetics and thermodynamics, respectively, and C8 is a possible site to generate the minor product. The formation mechanisms of biomarker 8-Cl- and 8-oxo-purine derivatives were also investigated. Additionally, the structure-kinetic reactivity relationship study reveals a good correlation between lg kobs-est and APT charge in all purine compounds compared to FED2 (HOMO), which proves again that the electrostatic interaction plays a key role. The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination.

Impact of changes in energy structure and industrial structure on green total factor productivity in the context of environmental protection-evidence from China.

To achieve high-quality economic development in the process of promoting the development of China's environment quality, and green economy, green total factor productivity is an important indicator to measure high-quality economic development. Therefore, it is of great significance to study the impact of changes in energy and industrial structure on green total factors. Each specific province in China is taken as the research object, and the green total factor productivity index into green technology efficiency and green technology progress are decomposed in this paper. On the basis of constructing the industrial structure upgrading index and energy structure upgrading index, a fixed-effect model and threshold regression model are used to analyze the influence of industrial structure and energy structure on green total factor productivity and its internal mechanism. Results shows that green total factor productivity, industrial structure and energy structure all show a trend of "continuous rise in small fluctuations," but there is a spatial disequilibrium; the upgrading and optimization of industrial structure and energy structure can effectively promote the improvement of green total factor productivity, and the growth mainly comes from the improvement of green technology progress, not the improvement of green technology efficiency; the impact of the improvement of industrial structure and energy structure on green technology efficiency has a significant nonlinear trend of increasing marginal effect; the upgrading of the industrial structure has a stronger role in promoting green total factor productivity in the central and western regions than in the eastern region; while the optimization of the energy structure has a significant promoting effect on green total factor productivity in the eastern region, but has a certain inhibitory effect on the central and western regions.

Suppressing HIFU interference in ultrasound images using 1D U-Net-based neural networks.

Objective.One big challenge with high-intensity focused ultrasound (HIFU) is that the intense acoustic interference generated by HIFU irradiation overwhelms the B-mode monitoring images, compromising monitoring effectiveness. This study aims to overcome this problem using a one-dimensional (1D) deep convolutional neural network.Approach. U-Net-based networks have been proven to be effective in image reconstruction and denoising, and the two-dimensional (2D) U-Net has already been investigated for suppressing HIFU interference in ultrasound monitoring images. In this study, we propose that the one-dimensional (1D) convolution in U-Net-based networks is more suitable for removing HIFU artifacts and can better recover the contaminated B-mode images compared to 2D convolution.Ex vivoandinvivoHIFU experiments were performed on a clinically equivalent ultrasound-guided HIFU platform to collect image data, and the 1D convolution in U-Net, Attention U-Net, U-Net++, and FUS-Net was applied to verify our proposal.Main results.All 1D U-Net-based networks were more effective in suppressing HIFU interference than their 2D counterparts, with over 30% improvement in terms of structural similarity (SSIM) to the uncontaminated B-mode images. Additionally, 1D U-Nets trained usingex vivodatasets demonstrated better generalization performance ininvivoexperiments.Significance.These findings indicate that the utilization of 1D convolution in U-Net-based networks offers great potential in addressing the challenges of monitoring in ultrasound-guided HIFU systems.

Intestinal Absorption of Nanoparticles to Reduce Oxidative Stress and Vasoconstriction for Treating Diabetic Nephropathy.

The etiology of diabetic nephropathy (DN) is complex, and the incidence is increasing year by year. The patient's kidney showed oxidative stress damage, increasing active oxygen species (ROS) content, and vasoconstriction. Due to poor drug solubility and low renal accumulation, the current treatment regimens have not effectively alleviated glomerulopathy and other kidney damage caused by DN. Therefore, it is of great significance to explore new treatment strategies and drug delivery systems. Here, we constructed an oral nanodelivery system (Tel/CAN@CS-DA) that reduced oxidative stress and vasoconstriction. Deoxycholic acid (DA)-modified nanoparticles entered into intestinal epithelial cells (Caco2 cells) via the bile acid biomimetic pathway, then escaped from the lysosomes and eventually spat out the cells, increasing the oral absorption of nanoparticles. Chitosan (CS) nanoparticles could achieve renal targeting through specific binding with a renal giant protein receptor and deliver drugs to renal tubule epithelial cells (HK-2 cells). In vitro studies also proved that telmisartan (Tel) and canagliflozin (CAN) effectively removed cellular reactive oxygen species (ROS) and reduced HK-2 cell apoptosis caused by high glucose. In the in vivo model induced by streptozotocin (STZ), the results showed that the nanosystem not only elevated AMPK protein expression, inhibited angiotensin II (Ang II) protein expression to effectively reduce oxidative stress level, dilated renal blood vessels but also reduced the degree of inflammation and fibrosis. Overall, Tel/CAN@CS-DA multifunctional oral nanosystem can effectively treat DN with low toxicity, which provides a new idea for the treatment of DN.

Azoramide ameliorates cadmium-induced cytotoxicity by inhibiting endoplasmic reticulum stress and suppressing oxidative stress.

Background: Cadmium (Cd) is hazardous to human health because of its cytotoxicity and long biological half-life. Azoramide is a small molecular agent that targets the endoplasmic reticulum (ER) and moderates the unfolded protein response. However, its role in Cd-induced cytotoxicity remains unclear. This study was performed to investigate the protective effect of azoramide against Cd-induced cytotoxicity and elucidate its underlying mechanisms. Methods: Inductively coupled plasma‒mass spectrometry was used to measure Cd concentrations in each tissue of ICR male mice. The human proximal tubule epithelial cell line HK-2 and the human retinal pigment epithelial cell line ARPE-19 were used in the in vitro study. Cell apoptosis was determined by DAPI staining, JC-1 staining, and annexin V/propidium iodide double staining. Intracellular oxidative stress was detected by MitoSOX red staining, western blot, and quantitative real-time PCR. Moreover, ER stress signaling, MAPK cascades, and autophagy signaling were analyzed by western blot. Results: The present data showed that Cd accumulated in various organs of ICR mice, and the concentrations of Cd in the studied organs, from high to low, were as follows: liver > kidney > testis > lung > spleen > eye. Our study demonstrated that azoramide inhibited ER stress by promoting BiP expression and suppressing the PERK-eIF2α-CHOP pathway. Additionally, we also found that azoramide significantly decreased ER stress-associated radical oxidative species production, attenuated p38 MAPK and JNK signaling, and inhibited autophagy, thus suppressing apoptosis in HK-2 and ARPE-19 cells. Conclusion: Our study investigated the effect of azoramide on Cd-induced cytotoxicity and revealed that azoramide may be a therapeutic drug for Cd poisoning.

Advances in the role of GPX3 in ovarian cancer (Review).

Ovarian cancer (OC) is the 5th most common malignancy in women, and the leading cause of death from gynecologic malignancies. Owing to tumor heterogeneity, lack of reliable early diagnostic methods and high incidence of chemotherapy resistance, the 5­year survival rate of patients with advanced OC remains low despite considerable advances in detection and therapeutic approaches. Therefore, identifying novel therapeutic targets to improve the prognosis of patients with OC is crucial. The expression of glutathione peroxidase 3 (GPX3) plays a crucial role in the growth, proliferation and differentiation of various malignant tumors. In OC, GPX3 is the only antioxidant enzyme the high expression of which is negatively correlated with the overall survival of patients. GPX3 may affect lipid metabolism in tumor stem cells by influencing redox homeostasis in the tumor microenvironment. The maintenance of stemness in OC stem cells (OCSCs) is strongly associated with poor prognosis and recurrence in patients. The aim of the present study was to review the role of GPX3 in OC and investigate the potential factors and effects of GPX3 on OCSCs. The findings of the current study offer novel potential targets for drug therapy in OC, enhance the theoretical foundation of OC drug therapy and provide valuable references for clinical treatment.

Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival.

Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries. Endothelin-converting enzyme-like 1 (ECEL1), a membrane-bound metallopeptidase, was initially identified as a molecule associated with nerve injuries. Damaged neurons exhibit a significant increase in the expression of ECEL1 following various types of nerve injuries, such as optic nerve injury and sciatic nerve injury. This study aimed to investigate the relationship between ECEL1 overexpression and the survival of injured MNs following BPRA injury. Our results observed a significant elevation in ECEL1 expression in injured MNs and positively correlated with MNs survival following BPRA injury. The transcription of ECEL1 is regulated by the transcription factors c-Jun and ATF3 in the context of BPRA injury, which is consistent with previous other nerve injuries study. In addition, the expression of TrkA gradually decreases in ECEL1-positive MNs and ECEL1 possibly preserves the activity of downstream AKT-GSK3ß pathway of TrkA in injured MNs. In conclusion, our results introduce a promising therapeutic molecular target to assist re-implantation surgery for the treatment of BPRA injury.

Transcription profiles and phenotype reveal global response of Staphylococcus aureus exposed to ultrasound and ultraviolet stressors.

Ultrasound and ultraviolet light have good inactivation performance against pathogens in sewage. In this study, the inactivation mechanisms of 60 kHz ultrasound and ultraviolet radiation against Staphylococcus aureus (S. aureus) were studied from the perspectives of cell phenotype and transcriptome for the first time. The results showed that both ultrasound and ultraviolet treatments had adverse impacts on the cellular morphology of S. aureus to varying degrees at cellular level. The transcriptomic analysis revealed that there were 225 and 1077 differentially expressed genes (DEGs) in the ultrasound and ultraviolet treatments, respectively. The result revealed that both ultrasound and ultraviolet could interfere with the expression of the genes involved in ABC transporters, amino acid and fatty acid metabolism to influence the membrane permeability. Besides the membrane permeability, ultraviolet also could disturb the ATP synthesis, DNA replication and cell division through restraining the expression of several genes related to carbohydrate metabolism, peptidoglycan synthesis, DNA-binding/repair protein synthesis. Compared with the single inactivation pathway of ultrasound, ultraviolet inactivation of S. aureus is multi-target and multi-pathway. We believe that the bactericidal mechanisms of ultrasound and ultraviolet radiation presented by this study could provide theoretical guidance for the synergistic inactivation of pathogens in sewage by ultrasound and ultraviolet radiation in the future.