Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins.

JOURNAL/nrgr/04.03/01300535-202501000-00032/figure1/v/2024-05-14T021156Z/r/image-tiff Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies.

Unveiling diabetic nephropathy: a novel diagnostic model through single-cell sequencing and co-expression analysis.

BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes that affects the kidneys. Disulfidptosis, a newly defined type of programmed cell death, has emerged as a potential area of interest, yet its significance in DN remains unexplored. METHODS: This study utilized single-cell sequencing data GSE131882 from GEO database combined with bulk transcriptome sequencing data GSE30122, GSE30528 and GSE30529 to investigate disulfidptosis in DN. Single-cell sequencing analysis was performed on samples from DN patients and healthy controls, focusing on cell heterogeneity and communication. Weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA) were employed to identify disulfidptosis-related gene sets and pathways. A diagnostic model was constructed using machine learning techniques based on identified genes, and immunocorrelation analysis was conducted to explore the relationship between key genes and immune cells. PCR validation was performed on blood samples from DN patients and healthy controls. RESULTS: The study revealed significant disulfidptosis heterogeneity and cell communication differences in DN. Specific targets related to disulfidptosis were identified, providing insights into the pathogenesis of DN. The diagnostic model demonstrated high accuracy in distinguishing DN from healthy samples across multiple datasets. Immunocorrelation analysis highlighted the complex interactions between immune cells and key disulfidptosis-related genes. PCR validation supported the differential expression of model genes VEGFA, MAGI2, THSD7A and ANKRD28 in DN. CONCLUSION: This research advances our understanding of DN by highlighting the role of disulfidptosis and identifying potential biomarkers for early detection and personalized treatment.

Novel therapeutic strategies and drugs for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Currently, drugs used to treat IPF in clinical practice exhibit severe side effects and limitations. To address these issues, this paper discusses the therapeutic effects of preclinical targeted drugs (such as STAT3 and TGF-ß/Smad pathway inhibitors, chitinase inhibitors, PI3K and phosphodiesterase inhibitors, etc.) and natural products on IPF. Through a summary of current research progress, it is found that natural products possess multitarget effects, stable therapeutic efficacy, low side effects, and nondrug dependence. Furthermore, we discuss the significant prospects of natural product molecules in combating fibrosis by influencing the immune system, expecting that current analytical data will aid in the development of new drugs or the investigation of active ingredients in natural products for potential IPF treatments in the future.

Designing Fast-Moving Antibacterial Microtorpedoes to Treat Lethal Bacterial Biofilm Infections.

Engineering fast-moving microrobot swarms that can physically disassemble bacterial biofilms and kill the bacteria released from the biofilms is a promising way to combat bacterial biofilm infections. Here, we report electrochemical design of Ag7O8NO3 microtorpedoes with outstanding antibacterial performance and meanwhile capable of moving at speeds of hundreds of body lengths per second in clinically used H2O2 aqueous solutions. These fast-moving antibacterial Ag7O8NO3 microtorpedoes could penetrate into and disintegrate the bacterial biofilms and, in turn, kill the bacteria released from the biofilms. Based on the understanding of the growth behavior of the microtorpedoes, we could fine-tune the morphology of the microtorpedoes to accelerate the moving speed and increase their penetration depth into the biofilms simply via controlling the potential waveforms. We further developed an automatic shaking method to selectively peel off the uniformly structured microtorpedoes from the electrode surface, realizing continuous electrochemical production of the microtorpedoes. Animal experiments proved that the microtorpedo swarms greatly increased the survival rate of the mice infected by lethal biofilms to >90%. We used the electrochemical method to design and massively produce uniformly structured fast-moving antibacterial microtorpedo swarms with application potentials in treatment of lethal bacterial biofilm infections.

Lipid remodelling and the conversion of lipids into sugars associated with tolerance to cadmium toxicity during white clover seed germination.

Cadmium (Cd) is a leading environmental issue worldwide. The current study was conducted to investigate Cd tolerance of 10 commercial white clover (Trifolium repens) cultivars during seed germination and to further explore differences in lipid remodelling, glycometabolism, and the conversion of lipids into sugars contributing to Cd tolerance in the early phase of seedling establishment as well as the accumulation of Cd in seedlings and mature plants. The results show that Cd stress significantly reduced seed germination of 10 cultivars. Compared to Cd-sensitive Sulky, Cd-tolerant Pixie accelerated amylolysis to produce more glucose, fructose, and sucrose by maintaining higher amylase and sucrase activities under Cd stress. Pixie maintained higher contents of various lipids, higher DGDG/MGDG ratio, and lower unsaturation levels of lipids, which could be beneficial to membrane stability and integrity as well as signal transduction in cells after being subjected to Cd stress. In addition, Pixie upregulated expression levels of key genes (TrACX1, TrACX4, TrSDP6, and TrPCK1) involved in the conversion of lipids into sugars for early seedling establishment under Cd stress. These findings indicate that lipid remodelling, enhanced glycometabolism, and accelerated conversion of lipids into sugars are important adaptive strategies for white clover seed germination and subsequent seedling establishment under Cd stress. In addition, Pixie not only accumulated more Cd in seedlings and mature plants than Sulky but also had significantly better growth and phytoremediation efficiency under Cd stress. Pixie could be used as a suitable and critical germplasm for the rehabilitation and re-establishment of Cd-contaminated areas.

Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory.

5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-ß-galactosidase (SA-ß-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

Light-Powered Directional Ion Transport via PFN-Br/MoS2 Heterogeneous Membranes: Band Alignment and Activation Energy Barrier Engineering.

Biological photoresponsive ion transport systems consistently attract researchers' attention owing to their remarkable functions of harvesting energy from nature and participating in visual perception systems. Designing and constructing artificial light-driven ion transport devices to mimic biological counterparts remains a challenge owing to fabrication limitations in nanoconfined spaces. Herein, a typical conjugated polyelectrolyte (PFN-Br) was assembled onto a laminated MoS2M using simple solution-processing vacuum filtration, resulting in a heterogeneous three- and two-dimensional nanoporous membrane. The designed band alignment between PFN-Br and MoS2 enables effective directional ion transport under irradiation in an equilibrium solution, even against a 30-fold concentration gradient. The staggered energy structure of PFN-Br and MoS2 enhances charge separation and establishes a photogenerated potential as the driving force for ion transport. Additionally, the activation energy barrier for ion transport across the heterogeneous membrane decreased by 60% after light irradiation, considerably improving ion transport flux. The easy fabrication and high performance of the membrane in light-powered ion transport provide promising approaches for designing nanofluidic devices with possible applications in energy conversion, light-enhanced biosensing, and photoresponsive ionic devices.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment: A Case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of patients with Epidermal growth factor receptor (EGFR) sensitive mutations in non-small cell lung cancer (NSCLC). CASE SUMMARY: A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment. Secondary pathological tissue biopsy confirmed squamous cell carcinoma (SCC) transformation. Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time, while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC. Notably, EGFR-TKIs resistance includes primary and acquired. Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs, with SCC transformation being relatively rare. Our results provide more detailed results of the patient's diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma. CONCLUSION: Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

High-Resolution and Large-Dynamic Range Fiber-Optic Sensors Based on Dual-Mode Direct Spectrum Interrogation Method.

Conventional optical fiber temperature/strain sensors often have to make compromises between the resolution and the dynamic range. Here we present a new method that meets the measurement requirements for both high resolution and large dynamic range. A high-quality optical fiber Fabry-Perot Interferometer (FPI) constructed using a pair of chirped fiber Bragg gratings is employed as the sensor and a dual-mode direct spectrum interrogation method is proposed to identify the small drift of external temperature or strain. As a proof-of-concept illustration, a temperature resolution of 0.2 °C within 30-130 °C is demonstrated. For strain sensing, the resolution can be 10 µÎµ within 0-1000 µÎµ. The measurement resolution can be improved further by routinely increasing the reflectivity of the CFBG and the cavity length and the sensor can also be mass-produced. This new sensing schema not only resolves the conflict between the resolution and the dynamic range of fiber-optic temperature/strain sensors but can also be extended to other sensors and measurands.

Photosynthetic bacteria-based whole-cell inorganic-biohybrid system for multimodal enhanced tumor radiotherapy.

The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2-), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2- production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

γ-Aminobutyric acid (GABA) priming alleviates acid-aluminum toxicity to roots of creeping bentgrass via enhancements in antioxidant defense and organic metabolites remodeling.

MAIN CONCLUSION: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots.

Nanoparticle-mediated celastrol ER targeting delivery amplify immunogenic cell death in melanoma.

INTRODUCTION: Chemoimmunotherapy, which benefits from the combination of chemotherapy and immunotherapy, has emerged as a promising strategy in cancer treatment. However, effectively inducing a robust immune response remains challenging due to the limited responsiveness across patients. Endoplasmic reticulum (ER) stress is essential for activating intracellular signaling pathways associated with immunogenic cell death (ICD), targeting drugs to ER might enhance ER stress and improve ICD-related immunotherapy. OBJECTIVES: To improve the immune response of Chemoimmunotherapy. METHODS: ER targeting nanoparticles TSE-CEL/NP were constructed to enhance immunogenic cancer cell death. Flow cytometry, confocal microscope, TEM and immunofluorescence were used to evaluate the ER targeting effect and immunogenic tumor cell death in vitro on B16F10 tumor cells. Unilateral and bilateral tumor models were constructed to investigate the efficacy of anti-tumor and immunotherapy in vivo. Lung metastasis B16F10 melanoma tumor-bearing mice were used to assess the anti-metastasis efficacy. RESULTS: TSE-CEL/NP could specially accumulate in ER, thereby induce ER stress. High ER stress trigger the exposure of CRT, the extracellular release of HMGB1 and ATP. These danger signals subsequently promote the recruitment and maturation of dendritic cells (DCs), which in turn increase the proliferation of cytotoxic T lymphocytes (CD8+ T cells), ultimately resulted in an improved immunotherapy efficacy against melanoma. Invivo experiments showed that TSE-CEL/NP exhibits excellent antitumor efficacy and triggers a strong immune response. CONCLUSION: Our findings demonstrated that celastrol ER targeting delivery could amplify immunogenic cell death in melanoma, which provide experimental basis for melanoma immunotherapy.

Breaking barriers: bacterial-microalgae symbiotic systems as a probiotic delivery system.

The gut microbiota is one of the essential contributors of the pathogenesis and progress of inflammatory bowel disease (IBD). Compared with first-line drug therapy, probiotic supplementation has emerged as a viable and secure therapeutic approach for managing IBD through the regulation of both the immune system and gut microbiota. Nevertheless, the efficacy of oral probiotic supplements is hindered by their susceptibility to the gastrointestinal barrier, leading to diminished bioavailability and restricted intestinal colonization. Here, we developed a bacteria-microalgae symbiosis system (EcN-SP) for targeted intestinal delivery of probiotics and highly effective treatment of colitis. The utilization of mircroalge Spirulina platensis (SP) as a natural carrier for the probiotic Escherichia coli Nissle 1917 (EcN) demonstrated potential benefits in promoting EcN proliferation, facilitating effective intestinal delivery and colonization. The alterations in the binding affinity of EcN-SP within the gastrointestinal environment, coupled with the distinctive structural properties of the SP carrier, served to overcome gastrointestinal barriers, minimizing transgastric EcN loss and enabling sustained intestinal retention and colonization. The oral administration of EcN-SP could effectively treat IBD by reducing the expression of intestinal inflammatory factors, maintaining the intestinal barrier and regulating the balance of gut microbiota. This probiotic delivery approach is inspired by symbiotic interactions found in nature and offers advantages in terms of feasibility, safety, and efficacy, thus holding significant promise for the management of gastrointestinal disorders.

Arginine Regulates Skeletal Muscle Fiber Type Formation via mTOR Signaling Pathway.

The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino acid, has been observed to promote the formation of slow-twitch muscle fibers in animal models. However, the precise molecular mechanisms are still unclear. This study investigates the role of Arg in skeletal muscle fiber composition and mitochondrial function through the mTOR signaling pathway. In vivo, 4-week C56BL/6J male mice were divided into three treatment groups and fed a basal diet supplemented with different concentrations of Arg in their drinking water. The trial lasted 7 weeks. The results show that Arg supplementation significantly improved endurance exercise performance, along with increased SDH enzyme activity and upregulated expression of the MyHC I, MyHC IIA, PGC-1α, and NRF1 genes in the gastrocnemius (GAS) and quadriceps (QUA) muscles compared to the control group. In addition, Arg activated the mTOR signaling pathway in the skeletal muscle of mice. In vitro experiments using cultured C2C12 myotubes demonstrated that Arg elevated the expression of slow-fiber genes (MyHC I and Tnnt1) as well as mitochondrial genes (PGC-1α, TFAM, MEF2C, and NRF1), whereas the effects of Arg were inhibited by the mTOR inhibitor rapamycin. In conclusion, these findings suggest that Arg modulates skeletal muscle fiber type towards slow-twitch fibers and enhances mitochondrial functions by upregulating gene expression through the mTOR signaling pathway.

Serum Macrophage Colony-Stimulating Factor Relates to the Severity and the Pregnancy Outcomes in Hypertensive Disorders Complicating Pregnancy.

PURPOSE: This study aimed to assess the predictive value of macrophage colony-stimulating factor (M-CSF) in the first trimester for hypertensive disorders complicating pregnancy (HDCP) and its association with disease severity and adverse pregnancy outcomes. HDCP pose significant risks to both maternal health and fetal health. M-CSF is implicated in the pathogenesis of HDCP by promoting inflammation and endothelial damage. METHODS: Serum levels of M-CSF were measured using an enzyme-linked immunosorbent assay, and clinical characteristics and pregnancy outcomes were compared between groups. RESULTS: Pregnant women with HDCP had significantly higher levels of proteinuria, systolic blood pressure, and diastolic blood pressure compared to those with normal pregnancy. Among patients with HDCP, the severity of disease correlated positively with serum levels of M-CSF. Furthermore, M-CSF levels in the first trimester were significantly associated with adverse pregnancy outcomes. The findings suggest that M-CSF may serve as a potential biomarker for predicting HDCP and its severity, as well as adverse pregnancy outcomes. CONCLUSIONS: Early detection and monitoring of M-CSF levels could aid in identifying high-risk pregnancies and implementing appropriate interventions to improve maternal and fetal outcomes.

Predicting brain edema and outcomes after thrombectomy in stroke: Frontal delta/alpha ratio as an optimal quantitative EEG index.

OBJECTIVE: We aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). METHODS: A total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. RESULTS: Significantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. CONCLUSIONS: QEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SIGNIFICANCE: QEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.

Rapid inference of antibiotic resistance and susceptibility for Klebsiella pneumoniae by clinical shotgun metagenomic sequencing.

OBJECTIVES: The study aimed to develop a genotypic antimicrobial resistance testing method for Klebsiella pneumoniae using metagenomic sequencing data. METHODS: We utilized Lasso regression on assembled genomes to identify genetic resistance determinants for six antibiotics (Gentamicin, Tobramycin, Imipenem, Meropenem, Ceftazidime, Trimethoprim/Sulfamethoxazole). The genetic features were weighted, grouped into clusters to establish classifier models. Origin species of detected antibiotic resistant gene (ARG) was determined by novel strategy integrating "possible species," "gene copy number calculation" and "species-specific kmers." The performance of the method was evaluated on retrospective case studies. RESULTS: Our study employed machine learning on 3928 K. pneumoniae isolates, yielding stable models with AUCs > 0.9 for various antibiotics. GenseqAMR, a read-based software, exhibited high accuracy (AUC 0.926-0.956) for short-read datasets. The integration of a species-specific kmer strategy significantly improved ARG-species attribution to an average accuracy of 96.67%. In a retrospective study of 191 K. pneumoniae-positive clinical specimens (0.68-93.39% genome coverage), GenseqAMR predicted 84.23% of AST results on average. It demonstrated 88.76-96.26% accuracy for resistance prediction, offering genotypic AST results with a shorter turnaround time (mean ± SD: 18.34 ± 0.87 hours) than traditional culture-based AST (60.15 ± 21.58 hours). Furthermore, a retrospective clinical case study involving 63 cases showed that GenseqAMR could lead to changes in clinical treatment for 24 (38.10%) cases, with 95.83% (23/24) of these changes deemed beneficial. CONCLUSIONS: In conclusion, GenseqAMR is a promising tool for quick and accurate AMR prediction in Klebsiella pneumoniae, with the potential to improve patient outcomes through timely adjustments in antibiotic treatment.

Analysis of the Current Status of Nurses' Knowledge of Pressure Injuries and Factors Influencing It in Shaanxi Province, China: A Cross-Sectional Study.

Background: Pressure injuries are present in all healthcare environments and not only pose a significant health risk to individuals but also impose a heavy economic burden on society and families. Nurses, as the primary caregivers responsible for the prevention and management of pressure injuries, have knowledge that directly determines the incidence of pressure injuries. Aim: To understand the current status of nurses' knowledge of pressure injuries in Shaanxi Province and the factors influencing it. Design: A cross-sectional survey. Methods: In April - May 2022, 16,599 nurses from hospitals at all levels in Shaanxi Province were selected as survey subjects by convenience sampling method. They were surveyed using the general information questionnaire and the Pieper-Zulkowski pressure injury Knowledge Questionnaire through the Questionnaire Star platform. Results: 16,599 nurses had a pressure injury knowledge score of (44.32±10.11). Wound description and pressure ulcer staging dimensions were less than 60% correct. Comparison of pressure injury knowledge scores of nursing staff with different genders, hospital levels, titles, education, whether they were specialized nurses in wound stoma when they last attended a lecture on pressure ulcers, when they last read literature or books on pressure ulcers, and whether they ever looked for information about pressure ulcers on the Internet showed that the differences were statistically significant (P < 0.05), which were the influencing factors of the knowledge scores of the nursing staff in Shaanxi Province. Conclusion: Clinical nurses' awareness of stress-related injuries still needs to be improved, and nursing administrators can improve the quality of pressure-related injury care by increasing nursing staff's awareness through continuing education, tiered training, and other measures.

Construction of Frustrated Lewis Pairs in Poly(heptazine imide) Nanosheets via Hydrogen Bonds for Boosting CO2 Photoreduction.

The creation of frustrated Lewis pairs on catalyst surface is an effective strategy for tuning CO2 activation. The critical step in the formation of frustrated Lewis pairs is the spatial effect of proximal Lewis acid-Lewis base pairs. Here, we demonstrate a facile surface functionalization methodology that enables hydrogen bonding between N and H atoms to mediate the construction of frustrated Lewis pairs in poly(heptazine imide), thereby increasing the propensity to activate CO2 molecules. Experimental and theoretical results show that the construction of active hydrogen bonding regions can facilitate the bending of CO2 molecules. Furthermore, the delocalization of electron clouds induced by the hydrogen bonding-mediated frustrated Lewis pairs can promote the heterolytic cleavage and photocatalytic conversion of CO2. This work highlights the potential of utilizing hydrogen bonding-mediated strategy in heterogeneously photocatalytic activation of CO2 over polymer materials.