Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

A personalized multitasking framework for real-time prediction of blood glucose levels in type 1 diabetes patients.

Real-time prediction of blood glucose levels (BGLs) in individuals with type 1 diabetes (T1D) presents considerable challenges. Accordingly, we present a personalized multitasking framework aimed to forecast blood glucose levels in patients. The patient data was initially categorized according to gender and age and subsequently utilized as input for a modified GRU network model, creating five prediction sub-models. The model hyperparameters were optimized and tuned after introducing the decay factor and incorporating the TCN network and attention mechanism into the GRU model. This step was undertaken to improve the capability of feature extraction. The Ohio T1DM clinical dataset was used to train and evaluate the performance of the proposed model. The metrics, including Root Mean Square Error (RMSE), Mean Absolute Error (MAE) and Clark Error Grid Analysis (EGA), were used to evaluate the performance. The results showed that the average RMSE and the MAE of the proposed model were 16.896 and 9.978 mg/dL, respectively, over the prediction horizon (PH) of 30 minutes. The average RMSE and the MAE were 28.881 and 19.347 mg/dL, respectively, over the PH of 60 min. The proposed model demonstrated excellent prediction accuracy. In addition, the EGA analysis showed that the proposed model accurately predicted 30-minute and 60-minute PH within zones A and B, demonstrating that the framework is clinically feasible. The proposed personalized multitask prediction model in this study offers robust assistance for clinical decision-making, playing a pivotal role in improving the outcomes of individuals with diabetes.

Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.

Eight Years and Beyond Longitudinal Changes of Peripapillary Structures on OCT in Adult Myopia.

PURPOSE: To investigate the long-term changes of peripapillary structures detected by enhanced depth imaging of OCT in adult myopia. DESIGN: Observational case series. METHODS: Myopic participants who had undergone a full baseline ophthalmologic examination and followed up with a minimum of 8 years were included. Using enhanced depth imaging of OCT, scans around the optic disc in the follow-up mode which enabled capturing of the same positions were performed in 65 eyes. The peripapillary parameters including the size of border tissue, Bruch's membrane opening (BMO), peripapillary choroidal thickness, and the angle between peripapillary Bruch's membrane and anterior sclera were manually delineated and measured. RESULTS: The axial length showed a significant elongation after a mean follow up time of 9.46±0.92 years. The rates of changes were 0.015±0.011 mm/y in the medium myopia group, and 0.057±0.039 mm/y in the high myopia group. At the last visit, the average border tissue length and BMO diameter were increased. The angle between peripapillary BM did not show significant change, while the angle between peripapillary sclera showed significant rise. In multivariate analysis, the border tissue elongation, BMO enlargement, and increased sclera angle were all associated with the change of axial length. The development of BM defect and inward protrusion of sclera on temporal peripapillary region was observed on 8 (34.8%) eyes in the high myopia group, along with an extreme thinning or disappearing of peripapillary choroid. CONCLUSION: A marked longitudinal changes of peripapillary structures including border tissue, BM, choroid and sclera could be observed in adult myopic eyes, which may impact the biomechanical environment around optic nerve head.

MiR-4763-3p accelerates lipopolysaccharide-induced cardiomyocyte apoptosis and inflammatory response by targeting IL10RA.

In order to investigate miR-4763-3p and associated genes' roles in myocarditis, AC16 cell line was divided into LPS + miR-4763-3p inhibitor, LPS + NC inhibitor, LPS + miR-4763-3p inhibitor + si-IL10RA and NC groups, and Q-PCR was used to find out whether miR-4763-3p was expressed; Targetscan, Genecards, and MiRDB were used to estimate the miR-4763-3p target; Targetscan was used to display binding sites. Western blot assay was undertaken to detect Bax, Bcl-2, and IL10RA expression. Proliferation and apoptosis were processed using CCK8 and the flow cytometry assay, respectively. Migration and invasion were confirmed utilizing Transwell test. ELISA assay was processed to show the content of IL-6, IL-1ß, IL-10 and TGF-ß in the cell culture supernatant. After being exposed to LPS, cardiomyocyte cells expressed more miR-4763-3p. MiR-4763-3p inhibitor accelerated proliferation, migration and invasion behavior, while it also decreased apoptosis rate in LPS-treated cardiomyocyte cells. MiR-4763-3p inhibitor attenuated the inflammatory response by up-regulating Bax expression and down-regulating Bcl-2 level in LPS-treated cardiomyocyte cells. In cardiomyocyte cells treated with LPS, MiR-4763-3p expression was elevated. si-IL10RA The miR-4763-3p inhibitor restored its effects. MiR-4763-3p accelerates lipopolysaccharide-induced cardiomyocyte apoptosis and inflammatory response by targeting IL10RA, which might be a potential target for myocarditis.

Right congenital pyriform sinus fistula.

.

Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage.

OBJECTIVE: Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury. METHODS: We established an AKI mouse model by intraperitoneal injection of cisplatin in vivo, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR. RESULTS: Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage in vitro. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated. CONCLUSION: Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI.

The effect of clean cooking on the social participation of middle-aged and older adults in China: A prospective cohort study.

BACKGROUND: Indoor air pollution stemming from the use of solid fuels, such as biomass and coal, is a significant public health concern, especially in developing countries. Understanding the connection between indoor air quality and social participation is essential for crafting effective interventions and enhancing the well-being of these populations. This study aims to investigate the influence of indoor air pollution on social participation among middle-aged and olderly individuals in China. METHODS: This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS), encompassing 17,711 samples, to investigate the link between cooking fuel type and social participation. Survival analysis Cox regression was used, complemented by logistic regression for supplementary analyses. FINDINGS: Upon accounting for confounding factors, the analysis revealed that individuals who consistently used clean fuels and those who switched to clean fuels exhibited a significantly higher likelihood of increased social participation compared to those using solid fuels. The hazard ratios were 1.31 (95 % CI: 1.19-1.44) and 1.39 (95 % CI: 1.28-1.51), respectively. These findings remained consistent across various regression models and showed no signs of population heterogeneity. Furthermore, this study found that in the investigation of mediating effects, chronic disease did not demonstrate any mediating effect on social participation. However, the mediating effects of depression level and IADL (Instrumental Activities of Daily Living) were significant, accounting for 1.82 % and 7.35 % of the impact of clean cooking on social participation, respectively. INTERPRETATION: This study provides compelling evidence that adopting clean cooking practices positively influences social participation among middle-aged and older individuals in China. We recommend that governments, communities, and individuals prioritize measures to enhance indoor air quality.

Accuracy of solid portion size measured on multiplanar volume rendering images for assessing invasiveness in lung adenocarcinoma manifesting as subsolid nodules.

Background: The solid component of subsolid nodules (SSNs) is closely associated with the invasiveness of lung adenocarcinoma, and its accurate assessment is crucial for selecting treatment method. Therefore, this study aimed to evaluate the accuracy of solid component size within SSNs measured on multiplanar volume rendering (MPVR) and compare it with the dimensions of invasive components on pathology. Methods: A pilot study was conducted using a chest phantom to determine the optimal MPVR threshold for the solid component within SSN, and then clinical validation was carried out by retrospective inclusion of patients with pathologically confirmed solitary SSN from October 2020 to October 2021. The radiological tumor size on MPVR and solid component size on MPVR (RSSm) and on lung window (RSSl) were measured. The size of the tumor and invasion were measured on the pathological section, and the invasion, fibrosis, and inflammation within SSNs were also recorded. The measurement difference between computed tomography (CT) and pathology, inter-observer and inter-measurement agreement were analyzed. Receiver operating characteristic (ROC) analysis and Bland-Altman plot were performed to evaluate the diagnostic efficiency of MPVR. Results: A total of 142 patients (mean age, 54±11 years, 39 men) were retrospectively enrolled in the clinical study, with 26 adenocarcinomas in situ, 92 minimally invasive adenocarcinomas (MIAs), and 24 invasive adenocarcinomas (IAs). The RSSl was significantly smaller than pathological invasion size with fair inter-measurement agreement [intraclass correlation coefficient (ICC) =0.562, P<0.001] and moderate interobserver agreement (ICC =0.761, P<0.001). The RSSm was significantly larger than pathological invasion size with the excellent inter-measurement agreement (ICC =0.829, P<0.001) and excellent (ICC =0.952, P<0.001) interobserver agreement. ROC analysis showed that the cutoff value of RSSm for differentiating adenocarcinoma in situ from MIA and MIA from IA was 1.85 and 6.45 mm (sensitivity: 93.8% and 95.5%, specificity: 85.7% and 88.2%, 95% confidence internal: 0.914-0.993 and 0.900-0.983), respectively. The positive predictive value-and negative predictive value of MPVR in predicting invasiveness were 92.8% and 100%, respectively. Conclusions: Using MPVR to predict the invasive degree of SSN had high accuracy and good inter-observer agreement, which is superior to lung window measurements and helpful for clinical decision-making.

Atomic-scale stress modulation of nanolaminate for micro-LED encapsulation.

Micro/nano-LEDs for augmented reality (AR) and virtual reality (VR) applications face the challenge that the edge effect in micro-LEDs becomes significant as the size of devices shrinks. This issue can be effectively addressed through thin-film encapsulation, where zero stress of the thin film is a crucial factor, apart from the barrier property. Herein, a stress-modulation strategy was developed through a binary-cycle atomic-layer deposition (ALD) process combining PEALD SiO2 (compressive stress) and thermal ALD Al2O3 (tensile stress) in the same process window. The hybrid ALD process allows avoiding extra thermal stress generation and enables precise modulation of the atomic-scale thickness, thereby allowing the fabrication of nanolaminates with modulated stress. The optical nanolaminate developed herein achieved a stress level of near-zero, representing one of the best among reported studies. The structural design, characterized by a high-low refractive index, tortuous permeation path, and ultra-thin thickness, remarkably improved the optical transmittance and barrier properties (8.68 × 10-6 g m-2 day-1) of the nanolaminate. Moreover, the micro-LED encapsulated with SA2/1 exhibited excellent stability under thermal cycling, damp heat, and applied stress conditions. The mechanical stability of the nanolaminate was due to the strong interaction between Si-O and Al-O and the abundance of Si-O-Al bonding in the interface. Overall, the ALD-coating process provides a new avenue for accurately controlling the stress on nanolaminates, and has potential application to bolster the reliability of optoelectronic devices.

Efficient removal of Cr (VI) from coal gangue by indigenous bacteria-YZ1 bacteria: Adsorption mechanism and reduction characteristics of extracellular polymer.

The existence of heavy metals (especially Cr (VI)) in coal gangue has brought great safety risks to the environment. The indigenous bacteria (YZ1 bacteria) were separated and applied for removing Cr (VI) from the coal gangue, in which its tolerance to Cr (VI) was explored. The removal mechanism of Cr (VI) was investigated with pyrite in coal gangue, metabolite organic acids and extracellular polymer of YZ1 bacteria. The concentration of Cr (VI) could be stabilized around 0.012 mg/L by the treatment with YZ1 bacteria. The Cr (VI) tolerance of YZ1 bacteria reached 60 mg/L, and the removal efficiency of Cr (VI) was more than 95% by using YZ1 bacteria combined with pyrite. The organic acids had a certain reducing ability to Cr (VI) (removal efficiency of less than 10%). The extracellular polymers (EPS) were protective for the YZ1 bacteria resisting to Cr (VI). The polysaccharides and Humic-like substances in the soluble extracellular polymers (S-EPS) had strong adsorption and reduction effect on Cr (VI), in which the tryptophan and tyrosine proteins in the bound extracellular polymers (LB-EPS and TB-EPS) could effectively promote the reduction of Cr (VI). YZ1 bacteria could obviously reduce the damage of Cr (VI) from coal gangue to the environment.

A Transferability-Based Method for Evaluating the Protein Representation Learning.

Self-supervised pre-trained language models have recently risen as a powerful approach in learning protein representations, showing exceptional effectiveness in various biological tasks, such as drug discovery. Amidst the evolving trend in protein language model development, there is an observable shift towards employing large-scale multimodal and multitask models. However, the predominant reliance on empirical assessments using specific benchmark datasets for evaluating these models raises concerns about the comprehensiveness and efficiency of current evaluation methods. Addressing this gap, our study introduces a novel quantitative approach for estimating the performance of transferring multi-task pre-trained protein representations to downstream tasks. This transferability-based method is designed to quantify the similarities in latent space distributions between pre-trained features and those fine-tuned for downstream tasks. It encompasses a broad spectrum, covering multiple domains and a variety of heterogeneous tasks. To validate this method, we constructed a diverse set of protein-specific pre-training tasks. The resulting protein representations were then evaluated across several downstream biological tasks. Our experimental results demonstrate a robust correlation between the transferability scores obtained using our method and the actual transfer performance observed. This significant correlation highlights the potential of our method as a more comprehensive and efficient tool for evaluating protein representation learning. Code and data are freely available at https://github.com/SIAT-code/OTMTD.

Experimental and simulated microplastics transport in saturated natural sediments: Impact of grain size and particle size.

Microplastics (MPs) present in terrestrial environments show potential leaching risk to deeper soil layers and aquifer systems, which threaten soil health and drinking water supply. However, little is known about the environmental fate of MPs in natural sediments. To examine the MPs transport mechanisms in natural sediments, column experiments were conducted using different natural sediments and MPs (10-150 µm) with conservative tracer. Particle breakthrough curves (BTCs) and retention profiles (RPs) were numerically interpreted in HYDRUS-1D using three different models to identify the most plausible deposition mechanism of MPs. Results show that the retention efficiency for a given particle size increased with decreasing grain size, and RPs exacerbated their hyper-exponential shape in finer sediments. Furthermore, the amounts of MPs present in the effluent increased to over 85 % as MPs size decreased to 10-20 µm in both gravel and coarse sand columns, while all larger MPs (125-150 µm) were retained in the coarse sand column. The modeling results suggested that the blocking mechanism becomes more important with increasing particle sizes. In particular, the attachment-detachment without blocking was the most suited parameterization to interpret the movement of small MPs, while a depth-dependent blocking approach was necessary to adequately describe the fate of larger particles.

Heat Stress Responsive Aux/IAA Protein, OsIAA29 Regulates Grain Filling Through OsARF17 Mediated Auxin Signaling Pathway.

High temperature during grain filling considerably reduces yield and quality in rice, but its molecular mechanisms are not fully understood. We investigated the functions of a seed preferentially expressed Aux/IAA gene, OsIAA29, under high temperature-stress in grain filling using CRISPR/Cas9, RNAi, and overexpression. We observed that the osiaa29 had a higher percentage of shrunken and chalkiness seed, as well as lower 1000-grain weight than ZH11 under high temperature. Meanwhile, the expression of OsIAA29 was induced and the IAA content was remarkably reduced in the ZH11 seeds under high temperature. In addition, OsIAA29 may enhance the transcriptional activation activity of OsARF17 through competition with OsIAA21 binding to OsARF17. Finally, chromatin immunoprecipitation quantitative real-time PCR (ChIP-qPCR) results proved that OsARF17 regulated expression of several starch and protein synthesis related genes (like OsPDIL1-1, OsSS1, OsNAC20, OsSBE1, and OsC2H2). Therefore, OsIAA29 regulates seed development in high temperature through competition with OsIAA21 in the binding to OsARF17, mediating auxin signaling pathway in rice. This study provides a theoretical basis and gene resources for auxin signaling and effective molecular design breeding.

Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.

Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients.

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.

Genomic characteristics of two strains of ESBL-producing Klebsiella pneumoniae ST268 isolated from different samples of one patient.

OBJECTIVES: This study reports the whole-genome sequences of two strains of extended-spectrum beta-lactamase (ESBL)-producing and multidrug-resistant (MDR) K. pneumoniae ST268 and explores their acquired antibiotic resistance genes (ARGs) and the mobile genetic elements (MGEs). METHODS: Two strains of K. pneumoniae ST268 were isolated from different samples of one patient. Assessment of antimicrobial susceptibility was performed, and then whole-genome sequencing was conducted. Acquired ARGs, insertion sequences, and transposons harboured by the two strains of K. pneumoniae ST268 were identified, and then the genetic contexts associated with the ARGs were analysed systematically. RESULTS: Two strains of K. pneumoniae ST268 were found to carry the 118.6-kb hybrid IncFIIK:IncQ1:repBR1701 plasmid. All the acquired ARGs carried by the IncF plasmid were found to be situated on the 25.3-kb MDR region bracketed by ISKpn19 and IS26, which was widely present in the plasmids in 14 STs of strains in K. pneumoniae but also in IncF plasmids from Shigella flexneri and Klebsiella quasipneumoniae. Notably, the IncF plasmids harbouring the 25.3-kb MDR region were geographically distributed mainly in China, and the pKP161637-1/pKP160802-1 in our study was the first report on the IncF plasmid carrying the 25.3-kb MDR region bracketed in K. pneumoniae ST268. CONCLUSIONS: Two strains of ESBL-producing K. pneumoniae ST268 with a MDR IncF plasmid were identified in a hospital in China. The ARGs were identified on the 25.3-kb MDR region, bracketed by ISKpn19 and IS26, of the IncF plasmids, which were present not only in the K. pneumoniae but also in the S. flexneri and K. quasipneumoniae.

Preparation and Application of Polyaluminum Ferric Sulfate from Red Mud: Behaviors of Leaching, Polymerizing, and Coagulation.

Red mud is a solid waste containing valuable components, such as aluminum and iron. This paper aims to recover aluminum and iron from red mud by acid leaching and prepare polyaluminum ferric sulfate (PAFS) to apply for the turbidity reduction treatment of coal slurry water. The behaviors of leaching, polymerizing, and coagulation were analyzed by leaching thermodynamics and advanced micro-detection methods. More than 90% of aluminum and 60% of iron in red mud were dissolved into the leaching solution by using 50% sulfuric acid (v/v) with 7 mL/g at 100 °C for 2 h, where the crystal lattice of cancrinite was significantly destroyed to promote the dissolution of aluminum. The low polymerization (Al + Fe)a, medium polymerization (Al + Fe)b, and high polymerization (Al + Fe)c could be generated in PAFS by adjusting the basicity of the leaching solution with 0.7-0.9. The removal efficiency of turbidity of wastewater could reach more than 95% by using PAFS at 25 mg/L in the pH range of 6.0-7.0. The turbidity reduction mechanism included not only the electric neutralization of (Al + Fe)a but also the adsorption of (Al + Fe)b and the entrapment effect of (Al + Fe)c. This current study contributes to the future development of red mud based on flocculants containing aluminum and iron for wastewater treatment.

Associations between Serum Mineral Nutrients, Gut Microbiota, and Risk of Neurological, Psychiatric, and Metabolic Diseases: A Comprehensive Mendelian Randomization Study.

Recent observational studies have reported associations between serum mineral nutrient levels, gut microbiota composition, and neurological, psychiatric, and metabolic diseases. However, the causal effects of mineral nutrients on gut microbiota and their causal associations with diseases remain unclear and require further investigation. This study aimed to identify the associations between serum mineral nutrients, gut microbiota, and risk of neurological, psychiatric, and metabolic diseases using Mendelian randomization (MR). We conducted an MR study using the large-scale genome-wide association study (GWAS) summary statistics of 5 serum mineral nutrients, 196 gut microbes at the phylum, order, family, and genus levels, and a variety of common neurological, psychiatric, and metabolic diseases. Initially, the independent causal associations of mineral nutrients and gut microbiota with diseases were examined by MR. Subsequently, the causal effect of mineral nutrients on gut microbiota was estimated to investigate whether specific gut microbes mediated the association between mineral nutrients and diseases. Finally, we performed sensitivity analyses to assess the robustness of the study results. After correcting for multiple testing, we identified a total of 33 causal relationships among mineral nutrients, gut microbiota, and diseases. Specifically, we found 4 causal relationships between 3 mineral nutrition traits and 3 disease traits, 15 causal associations between 14 gut microbiota traits and 6 disease traits, and 14 causal associations involving 4 mineral nutrition traits and 15 gut microbiota traits. Meanwhile, 118 suggestive associations were identified. The current study reveals multiple causal associations between serum mineral nutrients, gut microbiota, risk of neurological, psychiatric, and metabolic diseases, and potentially provides valuable insights for subsequent nutritional therapies.