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Accurately predicting the concentration of fine particulate matter (PM2.5) is crucial for evaluating air pollution levels and public exposure. Recent advancements have seen a significant rise in using deep learning (DL) models for forecasting PM2.5 concentrations. Nonetheless, there is a lack of unified and standardized frameworks for assessing the performance of DL-based PM2.5 prediction models. Here we extensively reviewed those DL-based hybrid models for forecasting PM2.5 levels according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We examined the similarities and differences among various DL models in predicting PM2.5 by comparing their complexity and effectiveness. We categorized PM2.5 DL methodologies into seven types based on performance and application conditions, including four types of DL-based models and three types of hybrid learning models. Our research indicates that established deep learning architectures are commonly used and respected for their efficiency. However, many of these models often fall short in terms of innovation and interpretability. Conversely, models hybrid with traditional approaches, like deterministic and statistical models, exhibit high interpretability but compromise on accuracy and speed. Besides, hybrid DL models, representing the pinnacle of innovation among the studied models, encounter issues with interpretability. We introduce a novel three-dimensional evaluation framework, i.e., Dataset-Method-Experiment Standard (DMES) to unify and standardize the evaluation for PM2.5 predictions using DL models. This review provides a framework for future evaluations of DL-based models, which could inspire researchers to standardize DL model usage in PM2.5 prediction and improve the quality of related studies.

Abstract Background Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. Methods A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. Results Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. Conclusions These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Background and objectivesThe oral and gut microbiota play significant roles in childhood asthma pathogenesis. However, the communication dynamics and pathogenic mechanisms by which oral microbiota influence gut microbiota and disease development remain incompletely understood. This study investigated potential mechanisms by which oral-originated gut microbiota, specifically Prevotella genus, may contribute to childhood asthma etiology.MethodsOral swab and fecal samples from 30 asthmatic children and 30 healthy controls were collected. Microbiome composition was characterized using 16S rRNA gene sequencing and metagenomics. Genetic distances identified potential oral-originated bacteria in asthmatic children. Functional validation assessed pro-inflammatory properties of in silico predicted microbial mimicry peptides from enriched asthma-associated species. Fecal metabolome profiling combined with metagenomic correlations explored links between gut microbiota and metabolism. HBE cells treated with Prevotella bivia culture supernatant were analyzed for lipid pathway impacts using UPLC-MS/MS.ResultsChildren with asthma exhibited distinct oral and gut microbiota structures. Prevotella bivia, P. disiens, P. oris and Bacteroides fragilis were enriched orally and intestinally in asthmatics, while Streptococcus thermophilus decreased. P. bivia, P. disiens and P. oris in asthmatic gut likely originated orally. Microbial peptides induced inflammatory cytokines from immune cells. Aberrant lipid pathways characterized asthmatic children. P. bivia increased pro-inflammatory and decreased anti-inflammatory lipid metabolites in HBE cells.ConclusionThis study provides evidence of Prevotella transfer from oral to gut microbiota in childhood asthma. Prevotella’s microbial mimicry peptides and effects on lipid metabolism contribute to disease pathogenesis by eliciting immune responses. Findings offer mechanistic insights into oral-gut connections in childhood asthma etiology.

Abstract Background Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce4+ to Ce3+ by doping Zr4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. Results The engineered Ce0.7Zr0.3O2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. Conclusion 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration. Graphical Abstract

Aquatic plants are fundamental for aquatic ecosystems. Understanding variations in geographic patterns of aquatic plant diversity across growth forms is important for conservation and restoration of aquatic ecosystems. Environmental drivers, including climate, climate heterogeneity, water chemistry, habitat availability and geodiversity, could influence aquatic plant diversity and species composition across communities, yet their relative impacts remain controversial. Here, we examined geographic patterns and drivers of species richness of Chinese aquatic plants with different growth forms. We compiled distributions of 656 aquatic plant species in China at 50 × 50 km2 resolutions, and estimated richness patterns for species with different growth forms (i.e., helophyte, emergent, floating-leaved, free-drifting and submerged) and range sizes. Hierarchical partitioning analysis was employed to evaluate the independent effects of different environmental drivers on species richness. The Sørensen dissimilarity index and Multiple Matrix Regression with Randomization were used to compare the relative effects of environment and dispersal limitation on species dissimilarity between grid cells. Overall species richness was highest in northeastern and southern China, although species richness patterns varied across growth forms. Among environmental drivers examined, climate was the key determinant of the species richness of helophyte, emergent, floating-leaved and free-drifting plants, while habitat availability and water chemistry best explained the richness of submerged species. The richness of narrow-ranged species was dominated by climate, while the strongest determinant of wide-ranged species richness varied across growth forms. Our study mapped the species richness patterns of aquatic plants in China and indicated that the relationship between aquatic plant richness and environment significantly differed between growth forms and between wide-ranged and narrow-ranged species. These findings indicate the necessity of distinguishing growth forms in studies related to aquatic plants, and suggest that future climate change might threaten the distribution of narrow-ranged aquatic plants.

IntroductionThe relationship between oral and gut microbiota in alcohol dependence (AD) is not well understood, particularly the effects of oral microbiota on the intestinal microbiota. The current study aimed to explore the association between oral and gut microbiota in AD to clarify whether oral microbiota could ectopically colonize into the gut.Methods16S rRNA sequence libraries were used to compare oral and gut microbial profiles in persons with AD and healthy controls (HC). Source Tracker and NetShift were used to identify bacteria responsible for ectopic colonization and indicate the driver function of ectopic colonization bacteria.ResultsThe α-diversity of oral microbiota and intestinal microbiota was significantly decreased in persons with AD (all p

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague–Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats.

Background and objectivesDisease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms.MethodsCOVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers.ResultsThe oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway.ConclusionThe oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19.

Cancer stem cells (CSCs) have been increasingly recognized in recent years. CSCs from human neural tumors are one of the root causes of metastatic tumor progression, therapeutic resistance and recurrence. However, there is a lack of comprehensive literature that systematically consolidates the biomarkers specific to CSCs in neurological cancers. Therefore, this review provides a comprehensive summary of cancer stem cell (CSC) biomarkers for neurological tumors such as glioma, meningioma, medulloblastoma and neurofibroma. It also points out the possible functions of these biomarkers in diagnosis, treatment and prognosis, providing a broader perspective. First, we quantitatively screened key words such as CSCs, biomarkers, and expression by bibliometric analysis and clarified the intrinsic connections between the key words. Then, we describe the CSC biomarkers of major neurological tumors and their pathway mechanisms, and provide an in-depth analysis of the commonalities and differences with the biomarkers of non-CSCs. In addition, many studies have shown that antipsychotic drugs can inhibit tumor growth and reduce the expression of CSC biomarkers, which facilitates targeted therapy against tumors in the nervous system. Therefore, this study will focus on the biomarkers of CSCs in the nervous system, hoping to provide guidance for future in-depth exploration and monitoring of neurological tumors for clinical applications.

Characterized by psychotic symptoms, negative symptoms and cognitive deficits, schizophrenia had a catastrophic effect on patients and their families. Multifaceted reliable evidence indicated that schizophrenia is a neurodevelopmental disorder. Microglia, the immune cells in central nervous system, related to many neurodevelopmental diseases. Microglia could affect neuronal survival, neuronal death and synaptic plasticity during neurodevelopment. Anomalous microglia during neurodevelopment may be associated with schizophrenia. Therefore, a hypothesis proposes that the abnormal function of microglia leads to the occurrence of schizophrenia. Nowadays, accumulating experiments between microglia and schizophrenia could afford unparalleled probability to assess this hypothesis. Herein, this review summarizes the latest supporting evidence in order to shed light on the mystery of microglia in schizophrenia.

Rituximab is emerging as a new steroid sparing agent in children with difficult-to-treat nephrotic syndrome due to its ability of depleting CD20-positive B cells. Life-threatening adverse events such as pneumocystis carinii pneumonia may occur even though it seems to be well tolerated. Since rituximab is wildly used in immune-mediated diseases, it is important to manage its severe adverse events. To explore the importance of early diagnosis and treatment of pneumocystis carinii pneumonia in children with primary nephrotic syndrome (PNS) after receiving rituximab therapy, we retrospectively analyzed the clinical data of PNS patients younger than 18 years old with pneumocystis carinii pneumonia who were hospitalized in our center. Clinical features and laboratory test results were retrieved from the electronic medical records. Severe pneumocystis carinii pneumonia occurred in one child with steroid resistant nephrotic syndrome and two with steroid dependent nephrotic syndrome patients after rituximab treatment. These patients were diagnosed in time by metagenomic next-generation sequencing (mNGS) for pathogen detection. Fortunately, all three patients survived after antifungal treatment and achieved complete remission eventually. In conclusion, early diagnosis by using mNGS and timely antifungal treatment is the key to successful management of pneumocystis carinii pneumonia in children with difficult-to-treat PNS.

Abstract Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.

Multimodality imaging is an advanced imaging tool for monitoring tumor behavior and therapy in vivo. In this study, we have developed a novel hybrid tri-modality system that includes two molecular imaging methods: positron emission computed tomography (PET) and fluorescence molecular imaging (FMI) and the anatomic imaging modality X-ray computed tomography (CT). The following paper describes the system development. Also, its imaging performance was tested in vitro (phantom) and in vivo, in Balb/c nude mice bearing a head and neck tumor xenograft treated with novel gene therapy [a new approach to the delivery of recombinant bacterial gene (IL-24-expressing strain)]. Using the tri-modality imaging system, we simultaneously monitored the therapeutic effect, including the apoptotic and necrotic induction within the tumor in vivo. The apoptotic induction was examined in real-time using an 18F-ML-10 tracer; the cell death was detected using ICG. A CT was used to evaluate the anatomical situation. An increased tumor inhibition (including tumor growth and tumor cell apoptosis) was observed in the treatment group compared to the control groups, which further confirmed the therapeutic effect of a new IL-24-expressing strain gene therapy on the tumor in vivo. By being able to offer concurrent morphological and functional information, our system is able to characterize malignant tissues more accurately. Therefore, this new tri-modality system (PET/CT/FMI) is an effective imaging tool for simultaneously investigating and monitoring tumor progression and therapy outcomes in vivo.

Near-zero carbon emission power (NZCEP) plants, consisting of gas-fired units; wind turbines; power-to-gas (P2G); and carbon capture, utilization and storage (CCUS) systems, have recently received a lot of attention due to their enormous benefits in reducing carbon emissions and increasing the consumption of renewable energy. However, a complex environment of interest and a combination of risks makes their development very slow. This paper establishes a risk analysis framework for NZCEP considering multi-stakeholder participation. Firstly, a synthetic risk factor system was constructed based on stakeholders’ interests. Subsequently, interval type II trapezoidal fuzzy numbers were used and final weights were calculated from both subjective and objective aspects. Finally, we applied an acronym in Portuguese of the interactive and multi-criteria decision-making (TODIM) method to site selection to achieve a balance of interests of all stakeholders. In addition, a case study was conducted. The case result demonstrates that Zhengzhou in Henan Province is the best choice for a NZCEP power plant. A further finding is that government plays an important role in the development of NZCEP plants, with site selection results being the most sensitive to changes in the government’s risk appetite. Moreover, human resources are an important factor in the siting of an NZCEP plant.

Abstract Background Primary nephrotic syndrome (PNS) is a common glomerular disease in children. T cell dysfunction plays a crucial role in the pathogenesis of PNS. Moreover, dysbiosis of gut microbiota contributes to immunological disorders. Whether the initial therapy of PNS affects gut microbiota remains an important question. Our study investigated compositional changes of gut microbiota after initial therapy. Methods Fecal samples of 20 children with PNS were collected before and after 4-week initial therapy. Total bacteria DNA were extracted and the V3-V4 regions of bacteria 16S ribosomal RNA gene were sequenced. The composition of gut microbiota before and after initial therapy was analyzed by bioinformatics methods. The function of altered gut microbiota was predicted with PICRUSt method. Results The richness and diversity of gut microbiota were similar before and after 4-week initial therapy. Gut microbiota at the phylum level was dominated by four phyla including Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria, but the increased relative abundance after initial therapy was found in Deinococcus-Thermus and Acidobacteria. At the genus level, the increased abundance of gut microbiota after initial therapy was observed in short chain fat acids (SCFA)-producing bacteria including Romboutsia, Stomatobaculum and Cloacibacillus (p

ABSTRACT Prednisone (PRED) is a synthetic glucocorticoid (GC) widely used in immune-mediated diseases for its immunosuppressive and anti-inflammatory properties. The effects of GC are achieved by genomic and nongenomic mechanisms. However, the nongenomic effects are largely unknown. Thus, we aimed to investigate how long-term prednisone therapy changes the composition of the gut microbiota and fecal metabolites in rats. Male Sprague-Dawley rats were randomly assigned to a control (CON) group and a PRED group, which received prednisone treatment daily for 6 weeks by gavage. The V3 to V4 regions of bacterial 16S rRNA genes were amplified and sequenced after the total bacterial DNA was extracted from fecal samples. The alpha and beta diversities were calculated. The compositional alteration of the gut microbiota at different taxonomic levels was analyzed using the Metastats method. Meanwhile, the fecal metabolites were quantitated in an ultra-performance liquid chromatography system. Similar microbial richness and diversity between the CON and PRED groups were indicated by the alpha diversity results. The gut microbial communities differed significantly between two groups. The relative abundances of the genera Eisenbergiella, Alistipes, and Clostridium XIVb decreased, whereas that of Anaerobacterium increased significantly in rats after the 6-week prednisone treatment. In total, 11 downregulated and 10 upregulated fecal metabolites were identified. Differential fecal metabolites were enriched in the pathways, including phenylalanine metabolism, butanoate metabolism, and propanoate metabolism. The lowered production of short-chain fatty acids was associated with the decreased relative abundance of the genera Alistipes and Clostridium XIVb and increased abundance of the genus Anaerobacterium. The composition of the gut microbiota and fecal metabolites was changed after long-term prednisone treatment. This may help us to understand the pharmacology of prednisone. IMPORTANCE Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver. Prolonged GC therapy causes anti-inflammatory effects; it also results in a variety of adverse events, including obesity, hypertension, psychiatric symptoms, and dyslipidemia. The therapeutic effects and adverse events of GCs may be associated with changes in the gut microbiota, as the host might be affected by the metabolites generated by the altered gut microbes. Thus, we investigated how long-term prednisone therapy changed the composition of the gut microbiota and fecal metabolites in rats. This study may shed new light on the pharmacology of prednisone.

Ordos Plateau is one of the primary sources of sediment in the Yellow River, and changes in regional soil erosion directly affect the ecological status of the lower reaches of the Yellow River. Many recent studies have been published using remote sensing (RS) and geographic information systems (GIS) to evaluate soil erosion. In this study, much satellite remote sensing data in the Google Earth Engine (GEE) can better track soil erosion protection, which is significant in guiding the ecological protection and restoration of the Ordos Plateau and the Yellow River basin. In this study, we used GEE to observe the changes in soil erosion in the Ordos area from 2013 to 2021. The Theil–Sen procedure and Mann–Kendall significance test methods were used to evaluate the trend of land erosion in the Ordos area from 2013 to 2021. Based on GEE, the RUSLE is applied to evaluate soil erosion and analyze the changing trend. As a result, (1) we found that the annual change of soil and water loss in the Ordos Plateau showed three stages: 2013–2015, 2016–2018, and 2018–2021. After 2018, soil loss decreased from 14 × 1017 Mg in 2018 to 4 × 1017 Mg in 2021, which indicates that the environmental restoration project started in 2018 has achieved encouraging results. (2) The results showed that 40.9% of the regional soil erosion trend showed a significant decline, and 45.7% of the regional soil erosion trend showed a slight decline. Only 13.3% of the regional soil erosion is on the rise. (3) The test results of different land use types show that 87.3% of soil erosion occurs in bare and cultivated land. Because the terrain of Ordos is relatively flat, 95.39–96.17% of soil erosion occurs in areas with a slope of 0 to 5. (4) The reliability of the RUSLE model based on the GEE platform is proved by regression model verification of observation data and model prediction results. (5) GEE’s cloud-based features can provide data and scripts to users in developing countries which lack sufficient observation data or the necessary computing resources to develop these data. The results show that GEE has robust analysis and processing ability, can analyze a large amount of data, and can provide efficient digital products for soil erosion research.

Hexavalent chromium [Cr(VI)] is a well-known occupational carcinogen, but the mechanisms contributing to DNA damage and cell cycle alternation have not been fully characterized. To study the dose-response effects of Cr(VI) on transcription, we exposed BEAS-2B cells to Cr(VI) at concentrations of 0.2, 0.6, and 1.8 μmol/L for 24 h. Here, we identified 1,484 differentially expressed genes (DEGs) in our transcript profiling data, with the majority of differentially expressed transcripts being downregulated. Our results also showed that these DEGs were enriched in pathways associated with the cell cycle, including DNA replication, chromatin assembly, and DNA repair. Using the differential expressed genes related to cell cycle, a weighted gene co-expression network was constructed and a key mRNA-lncRNA regulation module was identified under a scale-free network with topological properties. Additionally, key driver analysis (KDA) was applied to the mRNA-lncRNA regulation module to identify the driver genes. The KDA revealed that ARD3 (FDR = 1.46 × 10–22), SND1 (FDR = 5.24 × 10–8), and lnc-DHX32-2:1 (FDR = 1.43 × 10–17) were particularly highlighted in the category of G2/M, G1/S, and M phases. Moreover, several genes we identified exhibited great connectivity in our causal gene network with every key driver gene, including CDK14, POLA1, lnc-NCS1-2:1, and lnc-FOXK1-4:1 (all FDR < 0.05 in those phases). Together, these results obtained using mathematical approaches and bioinformatics algorithmics might provide potential new mechanisms involved in the cytotoxicity induced by Cr.

This study is aimed at exploring the mechanism by which the −254C>G single nucleotide polymorphism (SNP) on the transient receptor potential cation channel 6 (TRPC6) gene promoter could increase its activation in steroid-resistant nephrotic syndrome children of China. Plasmids containing the TRPC6 promoter region (with the −254C or G allele) were constructed and then transfected into human embryonic kidney (HEK) 293T cells and human podocytes. Luciferase assays were used to test the promoter activity in both cell lines with or without tumor necrosis factor-α (TNF-α) treatment, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) analysis was used to verify the transcription factor that could bind to this mutant sequence. Luciferase results indicate that the activity of the mutant promoter was greater than that of the normal promoter of the TRPC6 gene in both cell lines. We further predicted and verified that this variation was mediated by the nuclear factor kappa B (NF-κB) subunit RELA, and TNF-α significantly enhanced the transcription activity of TRPC6 with the −254G allele. In conclusion, the −254C>G SNP is a gain-of-function variation of the TRPC6 gene, and it is also an early and effective factor for predicting steroid-resistant nephrotic syndrome (SRNS) in Chinese children.

Background Drug addiction is a serious problem worldwide and is infuenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. Methods A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. Results Both single-SNP and haplotype tests revealed associations between illicit drug use and several immunerelated genes in the major histocompatibility complex (MHC) region (SNP association: log10BF=15.135, p=1.054e18; haplotype association: log10BF=20.925, p=2.065e-24). These genes may afect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide signifcant associations between rs3782886 (SNP association: log10BF=8.726, p=4.842e-11) in BRAP and rs671 (SNP association: log10BF=7.406, p=9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide signifcant association (haplotype association: log10BF=7.607, p=3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. Conclusions These fndings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches. [ABSTRACT FROM AUTHOR]