Applying 12 machine learning algorithms and Non-negative Matrix Factorization for robust prediction of lupus nephritis.

Lupus nephritis (LN) is a challenging condition with limited diagnostic and treatment options. In this study, we applied 12 distinct machine learning algorithms along with Non-negative Matrix Factorization (NMF) to analyze single-cell datasets from kidney biopsies, aiming to provide a comprehensive profile of LN. Through this analysis, we identified various immune cell populations and their roles in LN progression and constructed 102 machine learning-based immune-related gene (IRG) predictive models. The most effective models demonstrated high predictive accuracy, evidenced by Area Under the Curve (AUC) values, and were further validated in external cohorts. These models highlight six hub IRGs (CD14, CYBB, IFNGR1, IL1B, MSR1, and PLAUR) as key diagnostic markers for LN, showing remarkable diagnostic performance in both renal and peripheral blood cohorts, thus offering a novel approach for noninvasive LN diagnosis. Further clinical correlation analysis revealed that expressions of IFNGR1, PLAUR, and CYBB were negatively correlated with the glomerular filtration rate (GFR), while CYBB also positively correlated with proteinuria and serum creatinine levels, highlighting their roles in LN pathophysiology. Additionally, protein-protein interaction (PPI) analysis revealed significant networks involving hub IRGs, emphasizing the importance of the interleukin family and chemokines in LN pathogenesis. This study highlights the potential of integrating advanced genomic tools and machine learning algorithms to improve diagnosis and personalize management of complex autoimmune diseases like LN.

CD19 CAR-T treatment shows limited efficacy in r/r DLBCL with double expression and TP53 alterations.

OBJECT: Autologous CD19 chimeric antigen receptor T-cell therapy (CAR-T) significantly modifies the natural course of chemorefractory diffuse large B-cell lymphoma (DLBCL). However, 25% to 50% of patients with relapsed/refractory DLBCL still do not achieve remission. Therefore, investigating new molecular prognostic indicators that affect the effectiveness of CAR-T for DLBCL and developing novel combination therapies are crucial. METHODS: Data from 73 DLBCL patients who received CD19 CAR-T (Axi-cel or Relma-cel) were retrospectively collected from Shanghai Tongji Hospital of Tongji University, The Second Affiliated Hospital Zhejiang University School of Medicine, and The Affiliated People's Hospital of Ningbo University. Prior to CD19 CAR-T-cell transfusions, the patients received fludarabine and cyclophosphamide chemotherapy regimen. RESULTS: Our study revealed that relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) patients with both Double-expression (MYC > 40% and BCL2 > 50%) and TP53 alterations tend to have a poorer clinical prognosis after CAR-T therapy, even when CAR-T therapy is used in combination with other therapies. However, CAR-T therapy was found to be effective in patients with only TP53 alterations or DE status, suggesting that their prognosis is in line with that of patients without TP53 alterations or DE status. CONCLUSIONS: Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities.

Fugacity model covering abiotic and biotic matrices to investigate the transfer and fate of perfluoroalkyl acids in a large shallow lake of eastern China.

Solving the challenges faced during the measurement of the cross-interface transfer of perfluoroalkyl acids (PFAAs) in lakes is crucial for clarifying environmental behaviours of these chemicals and their efficient governance. This study developed a multimedia fugacity model based on the quantitative water-air-sediment interaction (QWASI) covering abiotic/biotic matrices to investigate the cross-interface transfer and fate of PFAAs in Luoma Lake, a typical PFAA-contaminated shallow lake in eastern China. The accuracy and reliability of the established model were confirmed using Percent bias and Monte Carlo simulation, respectively. Using the QWASI model, the multimedia transfer of the PFAAs and their accumulation and persistence in different sub-compartments were described and measured, and the differences among individual PFAAs were explored. The simulation results showed that the sedimentation and resuspension of PFAAs were the most intense cross-interfacial transfers, and the sediments served as a chemical sink in the long term. A significant negative correlation of NC-F (the number of CF bonds) with the relative outflow flux (TW·out-ct) but a positive correlation with the relative net transfer across the interface between water and aquatic plants (Tp-ct) was detected, indicating that the PFAA migration capacity decreased but the bioaccumulation potential increased with the CF bond number. The persistence in water (Pw) of individual PFAAs ranged from 19.65d (PFOA) to 32.22d (PFOS), with an average of 26.15d; their persistence in sediment (Ps) ranged from 432d (PFBA) to 3216d (PFOS), with an average of 1524d, increasing linearly with an increase in NC-F. The water advection flows into and out of the lake (QW·in and QW·out), the PFAA concentration of water inflow (CW·in), and bioconcentration factor of aquatic plants (BCFp) were the primary parameters sensitive to PFAAs in all sub-compartments, which are essential indexes for exploring promising remediation pathways for lacustrine PFAA contamination based on the fugacity model simulation.

Polyoxometalate-Based Metal-Organic Frameworks with Both Proton Acid and Multioxidative Active Sites: Highly Efficient Catalytic Synthesis of Quinazolinones.

Quinazolinone derivatives are an important class of pharmaceutical and pesticide intermediates, which are generally synthesized starting with the condensation reaction between aldehydes and 2-aminobenzamide to obtain corresponding intermediates and then oxidized to obtain the products. Although some catalysts have been developed currently for the synthesis of quinazolinone derivatives, their catalytic efficiency is relatively low because only the oxidative catalytic sites of the catalyst have been focused on. Herein, we synthesized three new polyoxometalate-based metal-organic frameworks, [CuI4(4,4'-bipy)7(Hn-1PMo12-nVnO40)]·2H2O (n = 1-3), which were formed by coordinating a Cu(I)-bipy complex with different Keggin-type phosphomolybdic acids. An important feature of these compounds is that they possess proton and multioxidative active sites [Cu(I) center and V(V) center]; thus, we applied them to the catalytic synthesis of quinazolinone derivatives. The results indicate that compound 3 has an excellent catalytic activity. Based on density functional theory calculations, it is speculated that protons participate in the aldehyde amine condensation reaction, which changes the reaction pathway and reduces the activation energy from 55.1 to 31.4 kcal/mol, thereby increasing the reaction rate significantly. Interestingly, Raman spectra and electron paramagnetic resonance measurements indicate the presence of CuIIOO• and •O2- during the oxidative dehydrogenation process, which facilitates the rapid consumption of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one intermediates, thereby promoting the chemical reaction to move toward the positive direction. Thanks to the synergistic effect of multicatalytic sites, compound 3 achieved highly efficient catalytic synthesis of quinazolinones with 99% yield in 1 h.

Alteration of ascending colon mucosal microbiota in patients after cholecystectomy.

BACKGROUND: Cholecystectomy is a successful treatment option for gallstones, although the incidence of colorectal cancer (CRC) has notably increased in post-cholecystectomy (PC) patients. However, it remains uncertain whether the altered mucosal microbiota in the ascending colon is related. AIM: To investigate the potential correlation between gut microbiota and the surgical procedure of cholecystectomy. METHODS: In total, 30 PC patients and 28 healthy controls underwent colonoscopies to collect mucosal biopsy samples. PC patients were divided based on their clinical features. Then, 16S-rRNA gene sequencing was used to analyze the amplicon, alpha diversity, beta diversity, and composition of the bacterial communities. Additionally, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) database, sourced from the Kyoto Encyclopedia of Genes and Genomes, was used to predict the functional capabilities of the bacteria. RESULTS: PC patients were comparable with healthy controls. However, PC patients older than 60 years had a distinct composition compared to those under 60 years old. Bacteroidetes richness was considerably higher at the phylum level in PC patients. Bacteroides, Parabacteroides, and Bilophila were more abundant in the PC group than in the control group. Furthermore, PC patients exhibited greater enrichment in metabolic pathways, specifically those related to lipopolysaccharide biosynthesis and vancomycin group antibiotic production, than controls. CONCLUSION: This study indicated that the mucosal microbiota in PC patients was altered, perhaps offering new perspectives on the treatment possibilities for CRC and diarrhea following cholecystectomy.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial.

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

Elucidating T cell dynamics and molecular mechanisms in syngeneic and allogeneic islet transplantation through single-cell RNA sequencing.

Islet transplantation is a promising therapy for diabetes treatment. However, the molecular underpinnings governing the immune response, particularly T-cell dynamics in syngeneic and allogeneic transplant settings, remain poorly understood. Understanding these T cell dynamics is crucial for enhancing graft acceptance and managing diabetes treatment more effectively. This study aimed to elucidate the molecular mechanisms, gene expression differences, biological pathway alterations, and intercellular communication patterns among T-cell subpopulations after syngeneic and allogeneic islet transplantation. Using single-cell RNA sequencing, we analyzed cellular heterogeneity and gene expression profiles using the Seurat package for quality control and dimensionality reduction through t-SNE. Differentially expressed genes (DEGs) were analyzed among different T cell subtypes. GSEA was conducted utilizing the HALLMARK gene sets from MSigDB, while CellChat was used to infer and visualize cell-cell communication networks. Our findings revealed genetic variations within T-cell subpopulations between syngeneic and allogeneic islet transplants. We identified significant DEGs across these conditions, highlighting molecular discrepancies that may underpin rejection or other immune responses. GSEA indicated activation of the interferon-alpha response in memory T cells and suppression in CD4+ helper and γδ T cells, whereas TNFα signaling via NFκB was particularly active in regulatory T cells, γδ T cells, proliferating T cells, and activated CD8+ T cells. CellChat analysis revealed complex communication patterns within T-cell subsets, notably between proliferating T cells and activated CD8+ T cells. In conclusion, our study provides a comprehensive molecular landscape of T-cell diversity in islet transplantation. The insights into specific gene upregulation in xenotransplants suggest potential targets for improving graft tolerance. The differential pathway activation across T-cell subsets underscores their distinct roles in immune responses posttransplantation.

Effects of household concrete floors on maternal and child health - the CRADLE trial: a randomised controlled trial protocol.

Introduction: Early life soil-transmitted helminth infection and diarrhea are associated with growth faltering, anemia, impaired child development, and mortality. Exposure to fecally contaminated soil inside the home may be a key contributor to enteric infections, and a large fraction of rural homes in low-income countries have soil floors. The objective of this study is to measure the effect of installing concrete floors in homes with soil floors on child soil-transmitted helminth infection and other maternal and child health outcomes in rural Bangladesh. Methods and analysis: The Cement-based flooRs AnD chiLd hEalth (CRADLE) trial is an individually randomised trial in Sirajganj and Tangail districts, Bangladesh. Households with a pregnant woman, a soil floor, walls that are not made of mud will be eligible, and no plan to relocate for 3 years. We will randomise 800 households to intervention or control (1:1) within geographic blocks of 10 households to account for strong geographic clustering of enteric infection. Laboratory staff and data analysts will be blinded; participants will be unblinded. We will install concrete floors when the birth cohort is in utero and measure outcomes at child ages 3, 6, 12, 18, and 24 months. The primary outcome is prevalence of any soil-transmitted helminth infection (Ascaris lumbricoides, Necator americanus, or Trichuris trichiura) detected by qPCR at 6, 12, 18, or 24 months follow-up in the birth cohort. Secondary outcomes include household floor and child hand contamination with E. coli, extended-spectrum beta-lactamase producing E. coli, and soil-transmitted helminth DNA; child diarrhea, growth, and cognitive development; and maternal stress and depression. Ethics and dissemination: Study protocols have been approved by institutional review boards at Stanford University and the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). We will report findings on ClinicalTrials.gov, in peer-reviewed publications, and in stakeholder workshops in Bangladesh. Trial registration number: NCT05372068, pre-results.

High expression of EBP is an adverse prognostic factor for de novo acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease, for which identifying reliable prognostic markers is critical for accurate clinical prognosis and treatment optimization. The inhibition of emopamil-binding protein gene (EBP) expression has been demonstrated to induce cancer cell death via depleting downstream sterols. Nevertheless, no comprehensive studies have been conducted specifically in tumors, including AML. METHOD: Herein, survival analyses were performed on the dataset obtained from The Cancer Genome Atlas (TCGA). Besides, the EBP levels were quantified using real-time qPCR in a cohort of 120 AML patients, and the value of EBP was further assessed using our clinical data. RESULTS: Patients with high EBP expression had worse overall survival (OS) and event-free survival (EFS) than patients with low EBP expression, both in the TCGA dataset and our clinical data. Additionally, white blood cell (WBC) counts were higher in patients with high EBP expression (P = 0.032). Moreover, in patients with intermediate-risk AML, it was discovered that elevated EBP expression was linked to a worse EFS (P = 0.038). Multivariate analysis demonstrated that high EBP expression was an independent prognostic factor in AML patients and was associated with a shorter OS and EFS (OS: P = 0.041; EFS: P = 0.017). Furthermore, the data revealed that transplantation in the high-EBP group led to an improvement in survival (OS: P = 0.001; EFS: P = 0.001). The same benefit was also observed in intermediate-risk AML patients (OS: P = 0.026; EFS: P = 0.026). CONCLUSION: Collectively, our findings indicated that high expression of EBP in AML patients was an adverse prognostic factor, but transplantation had the otential to alleviate its negative effects.

Direct Identification of O─O Bond Formation Through Three-Step Oxidation During Water Splitting by Operando Soft X-ray Absorption Spectroscopy.

Anionic redox allows the direct formation of O─O bonds from lattice oxygens and provides higher catalytic in the oxygen evolution reaction (OER) than does the conventional metal ion mechanism. While previous theories have predicted and experiments have suggested the possible O─O bond, it has not yet been directly observed in the OER process. In this study, operando soft X-ray absorption spectroscopy (sXAS) at the O K-edge and the operando Raman spectra is performed on layered double CoFe hydroxides (LDHs) after intercalation with [Cr(C2O4)3]3-, and revealed a three-step oxidation process, staring from Co2+ to Co3+, further to Co4+ (3d6L), and ultimately leading to the formation of O─O bonds and O2 evolution above a threshold voltage (1.4 V). In contrast, a gradual oxidation of Fe is observed in CoFe LDHs. The OER activity exhibits a significant enhancement, with the overpotential decreasing from 300 to 248 mV at 10 mA cm-2, following the intercalation of [Cr(C2O4)3]3- into CoFe LDHs, underscoring a crucial role of anionic redox in facilitating water splitting.

Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study.

BACKGROUND: Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results. OBJECTIVE: The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D). METHODS: Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)-adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users. RESULTS: This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA. CONCLUSION: Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.

The efficacy and safety of pH-responsive and photothermal-sensitive multifunctional nanoparticles loaded with cryptotanshinone for the treatment of gastric cancer.

A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti-gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near-infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH-responsive and NIR-triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti-GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.

AGAMOUS-LIKE 24 senses continuous inductive photoperiod in the inflorescence meristem to promote anthesis in chrysanthemum.

During the floral transition, many plant species including chrysanthemum (Chrysanthemum morifolium) require continuous photoperiodic stimulation for successful anthesis. Insufficient photoperiodic stimulation results in flower bud arrest or even failure. The molecular mechanisms underlying how continuous photoperiodic stimulation promotes anthesis are not well understood. Here, we reveal that in wild chrysanthemum (C. indicum), an obligate short-day (SD) plant, floral evocation is not limited to SD conditions. However, SD signals generated locally in the inflorescence meristem (IM) play a vital role in ensuring anthesis after floral commitment. Genetic analyses indicate that the florigen FLOWERING LOCUS T-LIKE3 (CiFTL3) plays an important role in floral evocation, but a lesser role in anthesis. Importantly, our data demonstrate that AGAMOUS-LIKE 24 (CiAGL24) is a critical component of SD signal perception in the IM to promote successful anthesis, and that floral evocation and anthesis are two separate developmental events in chrysanthemum. We further reveal that the central circadian clock component PSEUDO-RESPONSE REGULATOR 7 (CiPRR7) in the IM activates CiAGL24 expression in response to SD conditions. Moreover, our findings elucidate a negative feedback loop in which CiAGL24 and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (CiSOC1) modulate LEAFY (CiLFY) expression. Together, our results demonstrate that the CiPRR7-CiAGL24 module is vital for sustained SD signal perception in the IM to ensure successful anthesis in chrysanthemum.

Atopic diseases and the risk of alopecia areata among pre-teens and teenagers in Taiwan.

Background Alopecia areata (AA), a disorder of non-scarring hair loss with a variable relapsing and remitting course, is a common autoimmune disease in children. Although it often presents as several focal small patchy bald lesions, early onset AA can lead to a total loss of scalp hair, even body hairs, a severe subtype. Atopic diseases are common concurrent disorders in AA, especially among those with early onset severe type of hair loss. Whether atopic diseases increase the risk of AA in the paediatric population of Taiwan, remains unclear. Objective To identify if atopic diseases increase the risk of AA among pre-teens and teenagers in Taiwan. Methods From Taiwan National Health Insurance Database 2010, we used the claims data to clarify the risk of AA in pre-teens and teenagers with atopic diseases (atopic dermatitis, allergic conjunctivitis, asthma, allergic rhinitis and food allergy) as compared to the general population. Cox proportional hazards model yielded hazard ratios (HRs) to address the impact of atopic diseases, sex and age on AA risk after adjusting for covariates and subsequent stratified analyses. Results Overall, 21,070 children (10,535 patients with atopic diseases and 10,535 normal cohort) aged over nine years were recruited. During a follow-up of 15 years, 39 (0.37%) cases were identified to have AA in the atopic diseases group, while 11 (0.10%) had developed AA in the normal cohort. As compared with the normal population, the paediatric population with atopic diseases had a 9.66-fold higher risk of developing AA. The risk was greater for boys and increased with advanced age. In the atopic diseases group, pre-teens and teenagers with food allergies and Sjogren's syndrome were more likely to have AA. Limitations Only one ethnic group. Conclusion All atopic diseases enhanced the risk of developing AA in Taiwan pre-teens and teenagers. Children with atopic diseases should be monitored to look for the development of AA.

Antisense oligonucleotides enhance SLC20A2 expression and suppress brain calcification in a humanized mouse model.

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.

In-situ rapid cultivation of aerobic granular sludge in A/O bioreactor by using Ca(ClO)2 pretreating sludge.

The efficient utilization of residual sludge and the rapid cultivation of aerobic granular sludge in continuous-flow engineering applications present significant challenges. In this study, aerobic granular cultivation was fostered in a continuous-flow system using Ca(ClO)2-sludge carbon (Ca-SC). Ca-SC retained the original sludge properties, contributing to granular growth in an A/O bioreactor. By day 40, the granule diameters increased to 0.8 mm with the SVI30 decreased by 2.7 times. Moreover, Ca-SC facilitated protein secretion, reaching 98.06 mg/g VSS and enhanced the hydrophobicity to 68.4 %. The continuous-flow aerobic granular sludge exhibited a nutrient removal rate above 90 %. Furthermore, Tessaracoccus and Nitrospira were enriched to promote granular formation and nitrogen removal. The residual sludge was carbonized and reused in the traditional wastewater treatment process to culture granular sludge in situ, aiming to achieve "self-production and self-consumption" of sludge and promote the innovative model of "treating waste with waste" in urban sewage environmental restoration.

Inhibition of the P38 MAPK/NLRP3 pathway mitigates cognitive dysfunction and mood alterations in aged mice after abdominal surgery plus sevoflurane.

BACKGROUND: Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model. METHODS: C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3ß (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed. RESULTS: SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors. CONCLUSIONS: Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway.

Electronic and Atomic Structural Properties Associated with Enhanced Photodegradation Activity in Mo-Doped TiO2 Nanoparticles.

The efficacy and structural evolution of Mo-doped titania nanoparticles (MTNPs) as advanced photocatalysts for degrading methyl blue (MB) are investigated by X-ray absorption spectroscopy (XAS). The 3 wt % MTNP, characterized by uniform size and anatase structure, exhibits higher efficiency. The spectral analyses unveiled structural variations in the TiO6 octahedral structure and revealed an active site of the distorted square pyramidal structure symmetry (C4v). The in situ XAS spectra illustrate that MTNPs, particularly at 3 wt % doping, effectively enhanced the hole carriers in Ti 3d orbitals with a charge transfer to Mo 4d orbitals and impeded electron-hole pair merging, significantly enhancing the photodegradation under light illumination. This study deepens our understanding of the crucial role of Mo doping in optimizing TiO2 nanoparticle performance for efficient environmental remediation, showcasing the potential of MTNPs as sustainable photocatalytic materials.

Deconvoluting Surface and Bulk Charge Storage Processes in Redox-Active Oxides by Integrating Electrochemical and Optical Insights.

Redox-active transition metal oxides (TMOs) play crucial roles in diverse energy storage and conversion technologies, such as batteries and pseudocapacitors. These materials show intricate electrochemical charge storage processes, encompassing both bulk ion-intercalation, typical of battery electrodes, and pseudocapacitive-like behavior localized near the surfaces. However, understanding the underlying mechanisms of charge storage in redox-active TMOs is challenging due to the coexistence of these behaviors. In this study, we propose an integrated approach that combines operando electrochemical and optical techniques to disentangle the contributions of bulk and surface phenomena. Using birnessite δ-MnO2-x as a model system, we account for surface pseudocapacitive-like layers and employ a refined model that incorporates both surface reactions and bulk chemical diffusion. This methodology allows us to extract essential kinetic parameters, establishing a fundamental framework for unraveling surface and bulk electrochemical processes. This advancement provides a valuable tool for the rational design of energy storage devices, enhancing our ability to tailor these materials for specific applications.

CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant.

Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative CT (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using Pulmonary Function Tests (PFT) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from two large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFT were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CIT), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients -- 66 BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with Forced Expiratory Volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS) (P < 0.0001). CIT's distinguished 94% of participants with BOS versus non-BOS, 85% early BOS versus non-BOS, 92% early BOS versus NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) 0.84 (95% confidence interval [CI] 0.74-0.94) and early BOS with AUC 0.84 (95% CI 0.69 - 0.97). Quantitative CT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.