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Abstract Glioma is the most common malignant tumor in the central nervous system, and its unique pathogenesis often leads to poor treatment outcomes and prognosis. In 2021, the World Health Organization (WHO) divided gliomas into five categories based on their histological characteristics and molecular changes. Non-coding RNA is a type of RNA that does not encode proteins but can exert biological functions at the RNA level, and long non-coding RNA (lncRNA) is a type of non-coding RNA with a length exceeding 200 nt. It is controlled by various transcription factors and plays an indispensable role in the regulatory processes in various cells. Numerous studies have confirmed that the dysregulation of lncRNA is critical in the pathogenesis, progression, and malignancy of gliomas. Therefore, this article reviews the proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, glycolysis, stemness, and drug resistance changes caused by the dysregulation of lncRNA in gliomas, and summarizes their potential clinical significance in gliomas.

Wheat straw (WS) has long been subjected to rough treatment by traditional incineration, which not only results in the waste of biomass resources but also poses a risk of atmospheric pollution and is not conducive to the sustainable utilization of natural resources. With great humification potential, WS can be utilized as a valuable composting material. The study optimized the C/N ratio by mixing WS and chicken manure (CM) as composting raw materials, and found that this method could significantly improve the compost quality. In comparison to the conventional poplar woodchip (PW) conditioning, the incorporation of WS resulted in an elevated composting temperature, an extended high-temperature period, a more expeditious lignocellulose degradation, a notable enhancement in the organic matter content, a suppression of hydrogen sulfide production under low C/N ratio, and a promotion of elemental sulfur conversion, collectively contributing to an enhanced overall quality and environmental friendliness of the compost. Correlation analysis of microbial communities and environmental factors demonstrated that the mixed compost facilitated the growth of actinomycetes and sulfur-transforming bacteria. Additionally, structural equation model indicated that parameters such as temperature and pH value played a key role in the composting process.

The feasibility of the aerobic granulation of activated sludge was investigated in a continuous-flow anaerobic–anoxic–oxic system under gradient-controlled hydraulic loading on the surface of a cyclone separator. Concentrated domestic sewage was used. After 80 days of operation, 80% of activated sludge in the system was in the form of granular sludge with an average particle size of 373 μm. High removal efficiency was achieved for chemical oxygen demand (94.40%), NH4+-N (99.93%), total nitrogen (89.44%), and total phosphorus (96.92%). A batch study revealed that Pseudomonas (1.34%) and Dechloromonas (1.05%) as the main denitrifying phosphorus-accumulating organisms could efficiently remove phosphorus using nitrate as an electron acceptor, which improved the utilization efficiency of carbon sources and achieved simultaneous denitrification and phosphorus removal. Overall, the study demonstrates the feasibility of enhanced denitrification and phosphorus removal in a continuous-flow granular sludge system. The sludge system enables simultaneous nitrogen and phosphorus removal under low carbon-to-nitrogen ratios.

In this study, the effect of arsenic on the sulfamethoxazole (SMX) removal efficiency and microbial community structure was investigated over 60 days using the SBR process. The results showed that the presence of arsenic had no significant impact on the system performance, the removal efficiencies of two reactors, R1 (the control test) and R2 (with the addition of arsenic), were 13.36 ± 5.71 and 14.20 ± 5.27%, which were attributed to the adsorption of SMX by fulvic acid-like substances and tryptophan-like proteins of extracellular polymeric substances. Compared to the seed sludge, the species number indicated that R2 possessed the richer diversity, while R1 possessed the lower diversity on day 60, which might be relative to the transferring of antibiotic resistance genes (ARGs) in sludge bacterial communities; the minute amounts of arsenic could make the relative levels of Sul1 and Sul2 genes which encode ARGs of sulfonamides in R2 (2.07 and 2.47%) be higher than that in R1 (1.65 and 1.27%), which made the bacterial community of the R2 system more adaptable to SMX stress. Therefore, the minute amounts of arsenic weakened the effect of SMX on the system and enhanced the stability of the microbial community structure. HIGHLIGHTS The addition of arsenic has no significant effect on the removal efficiency of sulfamethoxazole (SMX).; The extracellular polymeric substances played an important role in the SMX removal in both R1 and R2 reactors.; The arsenic could promote antibiotic resistance geness transfer in sludge bacterial communities.; The arsenic enhanced the microbial adaptation to SMX stress.; The arsenic ensured the stability of the microbial community structure.;

A combined process, including As(III) oxidation and As removal by the fibrous anion exchange material FFA-1, was established to treat arsenite ([As(III)] = 10 mg L−1)-polluted groundwater. Both fixed-bed reactors (R1 and R2) were separately filled with pozzolana and FFA-1. After 72 h of inoculation and 10 days of operation, As(III) oxidation efficiency reached around 100% and the total As in the effluent was below 10 µg L−1 for over 100 days. Then, the combined system was stopped and a desorption experiment on the FFA-1 collected from R2 was carried out. The results revealed that the As trapped by the FFA-1 was distributed linearly along the axial length of R2, and the maximum capacity for removal of the FFA-1 from R2 was about 28 mg As g−1 FFA-1. Moreover, the anions’ competing test showed that they were preferentially sequestrated by the FFA-1 according to the following order: SO42− > PO43− ≈ AsO43− > NO3− at neutral pH. Furthermore, the microorganisms attached to the FFA-1, including some arsenite-oxidizing microorganisms (AsOBs), could be a beneficial complement to the As(III) oxidation and, thus, the total As removal. At the same time, the regeneration test proved that the As(V) interception capacity of FFA-1 was barely affected by the presence of biofilm. Additionally, the calculated operating cost showed that this combined process has great potential for the remediation of As-polluted groundwater.

This article examined the biological removal of high concentrated sulfamethazine (SMZ) antibiotics by the acclimatized activated sludge in lab-scale SBRs system. The removal of SMZ was characterized by a quick adsorption and a slow process of biodegradation. The adsorption capacity of activated sludge for SMZ was 44 and 47 µg SMZ/g SS, respectively, with the initial SMZ concentrations of 1 and 2 mg/L. The adsorption process fitted pseudo-second-order kinetic model. In a series of batch studies, with the increase of initial SMZ concentration that were 1, 2, 3, 5, 7 and 9 mg/L, 56.0%, 51.3%, 42.2%, 29.5%, 25.0% and 20.8% of influent SMZ were biodegraded within 24 h of biological reaction, respectively. The Monod equation applied to simulate SMZ biodegradation had a good coefficient of determination (R2 > 0.99). Furthermore, the results of HPLC demonstrated that the SMZ was not completely removed by the acclimatized activated sludge. From the analysis of LC-MS, 4 intermediates of SMZ biodegradation were identified: Sulfanilic Acid, 4-amino-N-(4,6-dimethyl-2 pyrimidin) benzene sulfonamide, N-(4,6-dimethyl-2-pyrimidin)-4-N-(benzene sulfonamide) benzene sulfonamide, N-(4,6-dimethyl-2-pyrimidin)-4-N-(4,6-dimethyl pyrimidine) benzene sulfonamide, and N-(4,6-dimethyl-2-pyrimidin)-4-N-(3-dimethyl-4-N sodium benzene sulfonamide) benzene sulfonamide.

Abstract Background Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. Methods In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. Results We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. Conclusions This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

Abstract Background The utilization of long reads for single nucleotide polymorphism (SNP) phasing has become popular, providing substantial support for research on human diseases and genetic studies in animals and plants. However, due to the complexity of the linkage relationships between SNP loci and sequencing errors in the reads, the recent methods still cannot yield satisfactory results. Results In this study, we present a graph-based algorithm, GCphase, which utilizes the minimum cut algorithm to perform phasing. First, based on alignment between long reads and the reference genome, GCphase filters out ambiguous SNP sites and useless read information. Second, GCphase constructs a graph in which a vertex represents alleles of an SNP locus and each edge represents the presence of read support; moreover, GCphase adopts a graph minimum-cut algorithm to phase the SNPs. Next, GCpahse uses two error correction steps to refine the phasing results obtained from the previous step, effectively reducing the error rate. Finally, GCphase obtains the phase block. GCphase was compared to three other methods, WhatsHap, HapCUT2, and LongPhase, on the Nanopore and PacBio long-read datasets. The code is available from https://github.com/baimawjy/GCphase . Conclusions Experimental results show that GCphase under different sequencing depths of different data has the least number of switch errors and the highest accuracy compared with other methods.

Abstract Background Although early hemivertebra (HV) resection and short fusion (within 4 segments) have been successful in treating congenital HV, there is limited research comparing the outcomes of the shortest-segment fusion (2 segments) versus 3 or 4 segments, particularly in young children. To evaluate the efficacy of posterior hemivertebrectomy combined with two or more segments fusion in children under the age of 10 years with a solitary simple lower thoracic or lumbar HV (T8-L5). Methods This retrospective study included patients under the age of 10 with lower thoracic or lumbar solitary simple HV who underwent hemivertebra resection (HVR) and transpedicular short fusion and were divided into HV ± 1 group (2 segment fusion) and HV ± 2 group (3 or 4-segment fusion). The study recorded preoperative, postoperative (1 week), and the latest follow-up radiographic parameters and complications. The results of the coronal and sagittal planes were analyzed, and the main curve, segmental scoliosis curve, compensatory scoliosis curve, segmental kyphosis curve, and trunk shift were compared. Results The study included 35 patients (15 in the HV ± 1 group and 20 in the HV ± 2 group) with a mean age of 5.26 ± 2.31 years and a mean follow-up of 22.54 months (12–68). The mean preoperative Cobb angle was 32.66° ± 7.339° (HV ± 1) and 29.31°±6.642° (HV ± 2). The final Cobb angle was 10.99°± 7.837° (HV ± 1) and 8.22° ± 4.295° (HV ± 2). The main curve corrected by 72% (HV ± 1), 75% (HV ± 2) postoperatively and 67% (HV ± 1), 72% (HV ± 2) at the final follow-up (P > 0.05). There were no significant differences in the correction of the segmental scoliosis curve, compensatory scoliosis curve, segmental kyphosis curve, and trunk shift between the HV ± 1 and HV ± 2 groups (P > 0.05). The unplanned reoperation rate for HV in the thoracolumbar region (T11-L2) is significantly higher (P = 0.038). Conclusion In the context of solitary simple lower thoracic or lumbar HV (T8-L5), HV ± 1 segment fusion suffices and yields comparable correction outcomes in the midterm period when compared to HV ± 2. The reoperation rate exhibited a statistically significant increase in the thoracolumbar region.

Abstract Particulate organic nitrates (pON) significantly contribute to the mass of organic aerosol and influence the nitrogen oxides cycle in the atmosphere, but their evolution and lifetime remain uncertain. This study performed simultaneous measurements on the anthropogenically affected surface site and the mountain site on top of the polluted planetary boundary layer (PBL). After aging in the PBL, organic nitrate was converted from primary sources (decreased from 8.7% to 4.3%) to secondary sources (increased from 6.3% to 36.1%), spanning from the surface to the mountain. The evaporation of more volatile inorganic nitrate and the production of secondary organic nitrate during aging in the PBL contributed to the enhanced pON fraction over the top of PBL. The contribution of light absorption by brown carbon increased by 57% at the top of PBL compared to the surface, consistent with the higher fraction of nitrogenous organic aerosols over the mountain. The results provide field evidence that the nitrogenous organic aerosols (OA) may be preserved by adding into secondary OA and significantly contribute to the enhanced importance of brown carbon after aging during vertical transport in the PBL.

Background: Early evaluation of prognosis in cardiogenic shock (CS) is crucial for tailored treatment selection. Both lactate clearance and lactate levels are considered useful prognostic biomarkers in patients with CS. However, there is yet no literature comparing the 6-hour lactate clearance rate (Δ6Lac) with lactate levels measured at admission (L1) and after 6 h (L2) to predict 30-day mortality in CS. Methods: In this observational cohort study, 95 patients with CS were treated at Department of Intensive Care Unit, Yiwu Central Hospital between January 2020 and December 2022. Of these, 88 patients met the eligibility criteria. The lactate levels were measured after admission (L1) as the baseline lactate value, and were measured after 6 h (L2) following admission. The primary endpoint of the study was survival rate at 30 days. A receiver operating characteristic curve was used for data analysis. Univariate and multivariate Cox regression analyses were performed based on Δ6Lac. Kaplan–Meier (KM) survival curves were generated to compare the 30-day survival rates among L1, L2, and Δ6Lac. Results: The Δ6Lac model showed the highest area under the curve value (0.839), followed by the L2 (0.805) and L1 (0.668) models. The Δ6Lac model showed a sensitivity of 84.2% and specificity of 75.4%. The L1 and L2 models had sensitivities of 57.9% each and specificities of 89.9% and 98.6%, respectively. The cut-off values for Δ6Lac, L1, and L2 were 18.2%, 6.7 mmol/L, and 6.1 mmol/L, respectively. Univariate Cox regression analysis revealed a significant association between Δ6Lac and 30-day mortality. After adjusting for five models in multivariate Cox regression, Δ6Lac remained a significant risk factor for 30-day mortality in patients with CS. In our fifth multivariate Cox regression model, Δ6Lac remained a risk factor associated with 30-day mortality (hazard ratio [HR]=5.14, 95% confidence interval [CI]: 1.48 to 17.89, P=0.010) as well as L2 (HR=8.42, 95% CI: 1.26 to 56.22, P=0.028). The KM survival curve analysis revealed that L1 >6.7 mmol/L (HR=8.08, 95% CI: 3.23 to 20.20, P 6.1 mmol/L (HR=25.97, 95% CI: 9.76 to 69.15, P

Abstract N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC–MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. With a favorable bioavailability of 24.0%, N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs. Graphical Abstract

Abstract Orphan diseases, exemplified by T-cell prolymphocytic leukemia, present inherent challenges due to limited data availability and complexities in effective care. This study delves into harnessing the potential of machine learning to enhance care strategies for orphan diseases, specifically focusing on allogeneic hematopoietic cell transplantation (allo-HCT) in T-cell prolymphocytic leukemia. The investigation evaluates how varying numbers of variables impact model performance, considering the rarity of the disease. Utilizing data from the Center for International Blood and Marrow Transplant Research, the study scrutinizes outcomes following allo-HCT for T-cell prolymphocytic leukemia. Diverse machine learning models were developed to forecast acute graft-versus-host disease (aGvHD) occurrence and its distinct grades post-allo-HCT. Assessment of model performance relied on balanced accuracy, F1 score, and ROC AUC metrics. The findings highlight the Linear Discriminant Analysis (LDA) classifier achieving the highest testing balanced accuracy of 0.58 in predicting aGvHD. However, challenges arose in its performance during multi-class classification tasks. While affirming the potential of machine learning in enhancing care for orphan diseases, the study underscores the impact of limited data and disease rarity on model performance.

Vacuum induction-melting gas atomization (VIGA) is considered a widely applied method to prepare metal powders. However, the nozzle clogging problem in the VIGA process seriously affects the continuity of production and greatly increases the economic and time costs. In the atomization initial stage, the existence of unsteady state atomization mainly results in the nozzle clogging challenge. To understand the formation mechanism of nozzle clogging, a computational fluid dynamics (CFD) model was established to simulate the influence of unsteady state atomization sequence on the primary atomization of alloy melt. Typically, there are two kinds of sequence including starting the gas before pooling the alloy (namely, GA) and pouring the alloy before opening the gas (AG). The movement trajectory of the alloy melt droplet at the end of the delivery-tube was clarified. Based on CFD simulation, the atomization sequence of AG and GA was precisely controlled in the atomization pressure range of 2.5 MPa, 3.5 MPa, and 4.5 MPa to address the nozzle clogging issue. In the GA process, relatively finer powder was obtained at 3.5 MPa without nozzle clogging occurring. In contrast, the AG process greatly reduces the probability of nozzle clogging at 2.5–4.5 MPa, the final prepared powder is coarser. The predicted results of industrial experiments and numerical simulations are consistent. This study provides theoretical support for understanding the formation mechanism of nozzle clogging during the VIGA process.

The accumulation of cadmium (Cd) in facility soil is attracting increasing attention. Reductive soil disinfestation (RSD) is an effective soil disinfection method, while also having a certain passivating effect on Cd. The application of organic matter is crucial for the success of RSD, but the reduction efficiencies of different organic materials vary. Here, five treatments, namely untreated soil (CK), bean dregs (BD), peanut dregs (PD), sesame dregs (SD), and apple dregs (AD) were applied, and their performances in Cd immobilization in Cd-contaminated soil were assessed. Changes in soil properties and microbial communities were monitored. The results showed that the overall soil pH following RSD treatment decreased significantly, while organic matter, hydrolyzed nitrogen, available phosphorus, available potassium, exchangeable calcium, and exchangeable magnesium increased significantly. Compared to CK, the exchangeable (EX)-Cd contents after treatments SD and AD significantly decreased by 25.4% and 23.7%, respectively. RSD led to significant changes in the composition of soil microbial communities. SD treatment significantly increased the number of soil fungal operational taxonomic units (OTU), while BD, PD, and SD significantly increased the relative abundances of Bacteroidetes, Chloroflexi, Deinococus Thermus, and Basidiomycota in bacterial communities. The Gemmatimonadetes phylum showed a highly significant negative correlation with EX-Cd, indicating that it might have a positive effect on the fixation of Cd in polluted soil. SD significantly reduced the Cd content in the above-ground parts of lettuce by 74.76%, and had the least impact on lettuce biomass. It can be inferred that RSD is an ecologically effective method for the remediation of Cd pollution in facility soil by improving soil characteristics and altering microbial community composition to reduce Cd activity. However, further in-depth research is needed to optimize the types and amounts of organic materials applied.

The phospholipid bilayer nanodiscs (LNDs), as a rapidly-developing tool in recent years, provide a natural bio-memebrane environment to maintain the native conformation and functions of membrane proteins as well as a versatile delivery vehicle for a variety of hydrophobic and hydrophilic drugs. We have seen unprecedented advantages of phospholipid bilayer nanodiscs in membrane protein structure characterization, biochemical and physiological studies of membrane proteins, membrane environment studies, drug discovery & development, and drug delivery. Many previous reviews have been mainly focused on the advantages of nanodiscs in membrane protein researches, but few have touched upon the importance and potential application of nanodiscs in pharmaceutical industries. This review will provide general description of the structural characteristics, advantages, classification, and applications of phospholipid nanodiscs, with particular focus on nanodisc-enabled membrane protein drug discovery & development as well as drug delivery.

Introduction Despite the favourable efficacy of antiretroviral therapy (ART), HIV/AIDS continues to impose significant disease burdens worldwide. This study aims to systematically review published prognostic prediction models for survival outcomes of treatment experienced people living with HIV (TE-PLHIV), to describe their characteristics, compare their performance and assess the risk of bias and real-world clinical utility.Methods and analysis Studies will be identified through a comprehensive search in PubMed, EMBASE, Scopus, the Cochrane Library, and OpenGrey databases. Two reviewers will independently conduct a selection of eligible studies, data extraction and critical appraisal. Included studies will be systematically summarised using appropriate tools designed for prognostic prediction modelling studies. Where applicable, evidence will be summarised with meta-analyses.Ethics and dissemination Ethical approval is not required because only available published data will be analysed. The results of this work will be published in a peer-reviewed journal.Systematic review registration PROSPERO registration number CRD42023412118.