Changing respiratory pathogens infection patterns after COVID-19 pandemic in Shanghai, China.

To assess the positive rate of 11 respiratory pathogens in 2023, providing a comprehensive summary and analysis of the respiratory infection patterns after COVID-19 pandemic. The study comprised 7544 inpatients suspected of respiratory infections who underwent respiratory pathogen multiplex polymerase chain reaction tests from July 2022 to December 31, 2023. We analyzed the positive rate of 11 pathogens over 18 months and the characterization of infection patterns among different age groups and immune states. Among 7544 patients (age range 4 months to 104 years, 44.99% female), the incidence of infected by at least one of the 11 pathogens was 26.07%. Children (55.18%, p < 0.05) experienced a significantly higher infection probability than adults (20.88%) and old (20.66%). Influenza A virus (8.63%), Mycoplasma pneumoniae (5.47%), and human rhinovirus (5.12%) were the most common pathogens. In children, M. pneumoniae (35.96%) replaced the predominant role of human respiratory syncytial virus (HRSV) (5.91%) in the pathogen spectrum. Age, immunosuppressed state, and respiratory chronic conditions were associated with a significantly higher risk of mixed infection. Immunosuppressed patients were more vulnerable to human coronavirus (4.64% vs. 1.65%, p < 0.05), human parainfluenza virus (3.46% vs. 1.69%, p < 0.05), and HRSV (2.27% vs. 0.55%, p < 0.05). Patterns in respiratory infections changed following regional epidemic control measures and the COVID-19 pandemic.

Fish oil supplementation and risk of incident systemic lupus erythematosus: a large population-based prospective study.

BACKGROUND: Although fish oil has been considered to have an anti-inflammatory effect and has been proven to play a beneficial role in the incidence of numerous diseases, the association between fish oil supplementation and the risk of systemic lupus erythematosus (SLE) is still unknown. This study aimed at evaluating the correlation between fish oil use and incident SLE in a large population-based prospective cohort. METHODS: 390,277 participants without SLE at baseline from the UK Biobank were enrolled. Fish oil use was ascertained through a touchscreen questionnaire at baseline. The incidence of SLE was identified by the International Classification of Diseases version 10 code in medical records or self-report. Cox proportional hazard models were employed to estimate the association between fish oil use and SLE risk. RESULTS: Fish oil users accounted for 31.47% of participants. During a median follow-up duration of 11.57 years, 141 participants without fish oil use (4.56/100 000 person-years) and 68 participants with fish oil use (4.78/100 000 person-years) developed SLE. In four models with adjustments for different amounts of confounders, there was no significant difference in the risk of SLE between fish oil users and fish oil non-users (all p-values > 0.05). In subgroup analyses, we found that fish oil supplementation was associated with a lower risk of SLE among females with ultraviolet radiation ≥ 3 h/day (hazard ratio: 0.63, 95% confidence interval: 0.40-0.98), which turned insignificant after further adjustment for female-related factors and sun protection measures. CONCLUSIONS: No significant association between fish oil use and overall incident SLE was observed, except in females exposed to prolonged ultraviolet radiation. Subgroup analysis suggested that females exposed to prolonged ultraviolet radiation might benefit from fish oil supplementation in terms of preventing SLE, but it needs to be confirmed in further studies.

Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage-myofibroblast transition.

Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-ß and iguratimod or SRC inhibitors in vitro, suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage-myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease.

Health risk assessment of lead via the ingestion pathway for preschool children in a typical heavy metal polluted area.

The problems of environmental lead (Pb) pollution caused by mining activities have attracted global attention. Preschool children are vulnerable to exposure to Pb from the environment. To investigate the health risk of multiple exposures to Pb via oral ingestion (soil, water, rice, wheat, and vegetables) for preschool children in typical polluted areas, in this study, preschool children in Baiyin city were selected as the potential receptors, Pb concentrations in 28 soil samples and 33 vegetable samples were collected and measured. In addition, the Pb concentrations in local water, rice, and wheat were obtained by searching the literature. The Monte Carlo simulation was used in the uncertainty and sensitivity analysis of the parameters. Results showed that Pb concentrations in spinach, tomato, cushaw, lettuce, broad bean, pea, eggplant, and radish exceeded the standards (GB 2762-2017), and 42.86% of soil samples exceeded screening values (GB 15618-2018). The non-carcinogenic risk was as high as 3.58. Vegetables and wheat were the major contributors in the oral ingestion pathway. Furthermore, the carcinogenic risk of preschool children was 6.02E-06, which was acceptable. Monte Carlo simulations showed that health risk assessment results were most likely to be influenced by Pb concentrations in the media. In conclusion, the food safety of vegetables in soil-polluted areas deserves more attention, and certain measures should be taken to reduce the health risks to preschool children.

Assessment of heavy metal pollution and preschool children health risk in urban street dusts from different functional areas in a typical industrial and mining city, NW China.

To assess the pollution characteristics and health risks associated with street dust exposure among preschool children in typical industrial and mining areas, we analyzed heavy metal concentrations of 20 urban street dusts in commercial area (CA), residential area (RA), scientific and educational area (SEA) and industrial and mining area (IMA) from Baiyin, NW China. The average concentrations of Cr, Mn, Ni, Cu, Zn, Cd, Pb, As and Hg were 614.96, 484.25, 1757.74, 6868.86, 893.19, 77.62, 1473.99, 15.01 and 0.59 mg·kg-1, respectively. The ecological risk indexes for Cd, Cu and Hg were found as 20,075.20, 1425.07 and 1174.86, respectively, and the ecological risk was extremely high. The pollution load indexes (PLI) were > 1 for all four functional areas. The total hazard index (THI) for different functional areas were more than 1, and the main exposure pathway for children was ingestion route. Heavy metals in street dust of the IMA had the highest THI for children (43.88), and HI of Pb was being most significant (17.38). In addition, the carcinogenic risk to children via the respiratory route was acceptable. Furthermore, factor analysis and cluster analysis classified heavy metals into two groups, indicating common anthropogenic sources for Cr, Ni, Cu, Zn, Cd, Pb, As and Hg. In conclusion, urban street dusts from industrial and mining area of Baiyin, NW China were found polluted by heavy metals and the pollution would pose an obvious non-carcinogenic risk to preschool children.

Systemic lupus erythematosus and antiphospholipid antibody syndrome associated Addison disease: A case report. / 系统性红斑狼疮、抗磷脂抗体综合征合并Addisonç— 1例.

Addison disease is rare, and it is rarer to coexist with systemic lupus erythematosus and antiphospholipid antibody syndrome. We hereby reported a middle-aged female who presented with nausea, vomit, skin and mucosa hyperpigmentation, hypotension, hyponatremia, and pulmonary infection after diagnosis of deep venous thrombosis of the left lower extremity and systemic lupus erythematosus in 2012. The patient was finally diagnosed with antiphospholipid antibody syndrome secondary to systemic lupus erythematosus with Addison disease after the examination, such as blood cortisol, adrenocorticotropic hormone rhythm, and antiphospholipid antibody, who was improved clinically after hormone, anti-infective, and anticoagulant treatment. The patient's condition was stable in the follow-up. In clinic, we should pay attention to adrenal damage in patients with connective tissue diseases such as systemic lupus erythematosus and antiphospholipid antibody syndrome, and be alert to the occurrence of adrenal crisis.

Molecular epidemiology and genetic variation analyses of porcine circovirus type 2 isolated from Yunnan Province in China from 2016-2019.

BACKGROUND: Porcine circovirus type 2 (PCV2) is the causative agent of porcine circovirus-associated disease (PCVAD). Its prevalence in swine herds was first reported in China in 2000. PCV2 infection causes immunosuppression that leads to multiple diseases, causing serious economic problems for the swine industry in China. Since information on the genetic variation of PCV2 in Yunnan province is limited, this study aims to investigate the molecular epidemiological and evolutionary characteristics of PCV2 from 2016 to 2019. METHODS: A total of 279 clinical samples were collected from different regions of Yunnan between 2016 to 2019, and PCV2 was detected by PCR. We then amplified full genomes from the positive samples, and the sequences were analysed for homology and genetic evolution. RESULTS: Overall, 60.93% (170/279) of the screened swine herd samples were positive for PCV2. We sequenced 15 Yunnan province PCV2 strains from positive samples. Analyses of the complete genomes and Cap genes led to the classification of the 15 Yunnan PCV2 strains into PCV2a (2 of 15), PCV2b (1of 15) and PCV2d (12 of 15). All strains shared 94.3-99.9% of their identities with the nucleotide sequences of complete genomes in this study and shared 94.2-99.9% identity with the reference sequences. All strains share 89.4-100% and 86.8-100% of their identities with the nucleotide and amino acid (aa) sequences of Cap, respectively. CONCLUSIONS: The results of this study provide evidence that PCV2a, PCV2b and PCV2d genotypes coexisted in Yunnan Province from 2016 to 2019, and the priority prevalence genotype was PCV2d. The data provide evidence for the increased genetic diversity and insights into the molecular epidemiology of PCV2. This study also provides basic data for the Yunnan province PCV2 molecular epidemiological survey and accumulates effective materials for the development of PCV2 vaccines.

TRANSPARENT TESTA 4-mediated flavonoids negatively affect embryonic fatty acid biosynthesis in Arabidopsis.

Flavonoids are involved in many physiological processes in plants. TRANSPARENT TESTA 4 (TT4) acts at the first step of flavonoid biosynthesis, and the loss of TT4 function causes a lack of flavonoid. Flavonoid deficiency is reportedly the main cause of increased fatty acid content in pale-coloured oilseeds, but details regarding the relationship between seed flavonoids and fatty acid biosynthesis are elusive. In this work, we applied a genetic strategy combined with biochemical and cytological assays to determine the effect of seed flavonoids on the biosynthesis of fatty acids in Arabidopsis thaliana. We showed that TT4-mediated flavonoids negatively affect embryonic fatty acid biosynthesis. A crossing experiment indicated that seed flavonoid biosynthesis and the impact of this process on fatty acid biosynthesis were controlled in a maternal line-dependent manner. Loss of TT4 function activated glycolysis in seed embryos, thereby enhancing fatty acid biosynthesis, but did not improve seed mucilage production. Moreover, loss of TT4 function reduced PIN-FORMED 4 expression and subsequently increased auxin accumulation in embryos. Pharmacologically and genetically elevated auxin levels enhanced seed fatty acid biosynthesis. These results indicated that flavonoids affect fatty acid biosynthesis by carbon source reallocation via regulation of WRINKLE1 and auxin transport.

Effect of high night temperature on storage lipids and transcriptome changes in developing seeds of oilseed rape.

Global warming causes a faster increase of night temperature than of day temperature in tropical and subtropical zones. Little is known about the effect of high night temperature on storage lipids and transcriptome changes in oilseed rape. This study compared the total fatty acids and fatty acid compositions in seeds of two oilseed rape cultivars between high and low night temperatures. Their transcriptome profiles were also analyzed. High night temperature significantly affected the total fatty acids and fatty acid compositions in seeds of both low and high oil content cultivars, namely Jiuer-13 and Zheyou-50, thereby resulting in 18.9% and 13.7% total fatty acid reductions, respectively. In particular, high night temperature decreased the relative proportions of C18:0 and C18:1 but increased the proportions of C18:2 and C18:3 in both cultivars. In-depth analysis of transcriptome profiles revealed that high night temperature up-regulated gibberellin signaling during the night-time. This up-regulation was associated with the active expression of genes involved in fatty acid catabolism, such as those in ß-oxidation and glyoxylate metabolism pathways. Although the effect of temperature on plant lipids has been previously examined, the present study is the first to focus on night temperature and its effect on the fatty acid composition in seeds.

TRANSPARENT TESTA2 regulates embryonic fatty acid biosynthesis by targeting FUSCA3 during the early developmental stage of Arabidopsis seeds.

TRANSPARENT TESTA2 (TT2) regulates the biosynthesis of proanthocyanidins in the seed coat of Arabidopsis. We recently found that TT2 also participates in inhibition of fatty acid (FA) biosynthesis in the seed embryo. However, the mechanism by which TT2 suppresses the accumulation of seed FA remains unclear. In this study, we show that TT2 is expressed in embryos at an early developmental stage. TT2 is directly bound to the regulatory region of FUSCA3 (FUS3), and mediates the expression of numerous genes in the FA biosynthesis pathway. These genes include BCCP2, CAC2, MOD1 and KASII, which encode proteins involved in the initial steps of FA chain formation, FAD2 and FAD3, which are responsible for FA desaturation, and FAE1, which catalyzes very-long-chain FA elongation. Loss of function of TT2 results in reduced expression of GLABRA2 but does not cause a significant reduction in the mucilage attached to the seed coats, which competes with FA for photosynthates. TT2 is expressed in both maternal seed coats and embryonic tissues, but proanthocyanidins are only found in wild-type seed coats and not in embryonic tissues. The amount of proanthocyanidins in the seed coat is negatively correlated with the amount of FAs in the embryo.

OsMOGS is required for N-glycan formation and auxin-mediated root development in rice (Oryza sativa L.).

N-glycosylation is a major modification of glycoproteins in eukaryotic cells. In Arabidopsis, great progress has been made in functional analysis of N-glycan production, however there are few studies in monocotyledons. Here, we characterized a rice (Oryza sativa L.) osmogs mutant with shortened roots and isolated a gene that coded a putative mannosyl-oligosaccharide glucosidase (OsMOGS), an ortholog of α-glucosidase I in Arabidopsis, which trims the terminal glucosyl residue of the oligosaccharide chain of nascent peptides in the endoplasmic reticulum (ER). OsMOGS is strongly expressed in rapidly cell-dividing tissues and OsMOGS protein is localized in the ER. Mutation of OsMOGS entirely blocked N-glycan maturation and inhibited high-mannose N-glycan formation. The osmogs mutant exhibited severe defects in root cell division and elongation, resulting in a short-root phenotype. In addition, osmogs plants had impaired root hair formation and elongation, and reduced root epidemic cell wall thickness due to decreased cellulose synthesis. Further analysis showed that auxin content and polar transport in osmogs roots were reduced due to incomplete N-glycosylation of the B subfamily of ATP-binding cassette transporter proteins (ABCBs). Our results demonstrate that involvement of OsMOGS in N-glycan formation is required for auxin-mediated root development in rice.

TRANSPARENT TESTA8 Inhibits Seed Fatty Acid Accumulation by Targeting Several Seed Development Regulators in Arabidopsis.

Fatty acids (FAs) and FA-derived complex lipids play important roles in plant growth and vegetative development and are a class of prominent metabolites stored in mature seeds. The factors and regulatory networks that control FA accumulation in plant seeds remain largely unknown. The role of TRANSPARENT TESTA8 (TT8) in the regulation of flavonoid biosynthesis and the formation of seed coat color is extensively studied; however, its function in affecting seed FA biosynthesis is poorly understood. In this article, we show that Arabidopsis (Arabidopsis thaliana) TT8 acts maternally to affect seed FA biosynthesis and inhibits seed FA accumulation by down-regulating a group of genes either critical to embryonic development or important in the FA biosynthesis pathway. Moreover, the tt8 mutation resulted in reduced deposition of protein in seeds during maturation. Posttranslational activation of a TT8-GLUCOCORTICOID RECEPTOR fusion protein and chromatin immunoprecipitation assays demonstrated that TT8 represses the activities of LEAFY COTYLEDON1, LEAFY COTYLEDON2, and FUSCA3, the critical transcriptional factors important for seed development, as well as CYTIDINEDIPHOSPHATE DIACYLGLYCEROL SYNTHASE2, which mediates glycerolipid biosynthesis. These results help us to understand the entire function of TT8 and increase our knowledge of the complicated networks regulating the formation of FA-derived complex lipids in plant seeds.

The Environment and Children's Health Care in Northwest China.

BACKGROUND: Industrialization in the northwest provinces of the People's Republic of China is accelerating rapid increases in early life environmental exposures, yet no publications have assessed health care provider capacity to manage common hazards. METHODS: To assess provider attitudes and beliefs regarding the environment in children's health, determine self-efficacy in managing concerns, and identify common approaches to managing patients with significant exposures or environmentally-mediated conditions, a two-page survey was administered to pediatricians, child care specialists, and nurses in five provinces (Gansu, Shaanxi, Xinjiang, Qinghai, and Ningxia). Descriptive and multivariable analyses assessed predictors of strong self-efficacy, beliefs or attitudes. RESULTS: 960 surveys were completed with <5% refusal; 695 (72.3%) were valid for statistical analyses. The role of environment in health was rated highly (mean 4.35 on a 1-5 scale). Self-efficacy reported with managing lead, pesticide, air pollution, mercury, mold and polychlorinated biphenyl exposures were generally modest (2.22-2.52 mean). 95.4% reported patients affected with 11.9% reporting seeing >20 affected patients. Only 12.0% reported specific training in environmental history taking, and 12.0% reported owning a text on children's environmental health. Geographic disparities were most prominent in multivariable analyses, with stronger beliefs in environmental causation yet lower self-efficacy in managing exposures in the northwestern-most province. CONCLUSIONS: Health care providers in Northwest China have strong beliefs regarding the role of environment in children's health, and frequently identify affected children. Few are trained in environmental history taking or rate self-efficacy highly in managing common hazards. Enhancing provider capacity has promise for improving children's health in the region.

Saa3 promotes pro-inflammatory macrophage differentiation and contributes to sepsis-induced AKI.

Sepsis-induced acute kidney injury (SAKI) is a life-threatening condition with complex pathophysiology, often exacerbated by immune cell dysregulation. In this comprehensive study, we leverage publicly available single-cell RNA sequencing (scRNA-seq) datasets to unravel the intricate immune responses occurring during SAKI, shedding light on macrophages as critical players. Specifically, we identify Saa3, a gene primarily expressed in macrophages, as a potent pro-inflammatory cytokine in SAKI. Saa3hi Ccl2hi monocyte-derived infiltrated macrophages (IMs) emerge as a central effector subset, fostering inflammation, and directly engaging with renal cells. Our findings suggest that Saa3 may be a promising predictive marker of SAKI, although further exploration of human homologs is warranted.

Gastrodinol derivatives and prenylated flavones from the flower branch of Gastrodia elata.

Based on the research progress and traditional usage with whole herbal of the TCM "Tianma", chemical studies herein on the flower branch of Gastrodia elata were carried out in-depth and got 13 compounds including the gastrodinols (1-4), the flavonoid morins (5-8, 11-12), together with the specialist mulberrofurans (9, 13) and gastrodiamide (10) for the first time from the species. The antibacterial and cholinesterase inhibitory activities were then evaluated and the results showed that compounds 5, 11, 12, 13 have good activity against anti-methicillin-resistant Staphylococcus aureus, and compounds 9, 13 had good acetylcholinesterase inhibitory activity. All these results provide new chemical composition for better understanding the traditional application of "Tianma" and for exploring new pharmacological ingredients.

The PP2A inhibitor LB-100 mitigates lupus nephritis by suppressing tertiary lymphoid structure formation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase that participates in regulating multiple signaling pathways. Inhibition of PP2A has been implicated in the treatment of various diseases. LB-100, a small molecule inhibitor of PP2A, has demonstrated anti-tumor therapeutic effects and high safety profile in preclinical experiments. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in both spontaneous and R848-induced lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLSs) in the kidneys of two distinct lupus mouse models. The levels of signature genes of TLS were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokine production and inhibited TLS formation. In addition, we confirmed that inhibition or knockdown of PP2A reduced the production of T cell-related chemokines by renal tubular epithelial cells (RTEC). In summary, our study highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for treating LN and other autoimmune diseases.

The effect of transparent TESTA2 on seed fatty acid biosynthesis and tolerance to environmental stresses during young seedling establishment in Arabidopsis.

In plants, fatty acids (FAs) and FA-derived complex lipids are major carbon and energy reserves in seeds. They are essential components of cellular membranes and cellular signal or hormone molecules. Although TRANSPARENT TESTA2 (TT2) is well studied for its function in regulating proanthocyanidin biosynthesis in the seed coat, little attention has been given to its role in affecting seed FA accumulation and tolerance to environmental stresses. We demonstrate that the tt2 mutation remarkably increased the seed FA content, decreased seed weight, and altered the FA composition. The increase in FA content in the tt2 seeds was due to the relative decrease of seed coat proportion as well as the more efficient FA synthesis in the tt2 embryo. Microarray analysis revealed that tt2 mutation up-regulated a group of genes critical to FA biosynthesis and embryonic development. The mutation also altered the gene expressions that respond to stress. The microarray analysis discovered that the increase in FA accumulation of the tt2 seeds were accompanied by the significant up-regulation of FUSCA3, a transcriptional factor for embryonic development and FATTY ACID ELONGASE1, which catalyzes the elongation of FA chains. Moreover, lower seed protein accumulation during seed maturation also contributed to the increased seed FA accumulation in tt2 mutants. This study advances the understanding of the TT2 gene in seed FA accumulation and abiotic stresses during seed germination and seedling establishment.

[Distribution of waist circumference and waist-to-height ratio for 7-18 children and adolescents in Gansu Province].

OBJECTIVE: To understand the percentile normal of waist circumference and waist-to-height ratio for 7-18 children and adolescents in Gansu Province and to analyze their distribution and growth trend. METHODS: A stratified cluster representative sample of 6600 urban and rural children aged 7-18 years in Gansu Province was selected. To measure their waist circumference and height and establish the norm of waist circumference and waist-to-height ratio with percentile method. To compare them with the domestic correlation data. RESULTS: Sex-age specific percentiles of P5, P10, P25, P50, P75, P90, P95 of waist circumference and waist-to-height ratio for 7-18 children in Gansu Province were accessed. The P50 of waist circumference was increasing year by year and crossed two times, but that of waist-to-height ratio fluctuated slightly. A comparison of the P50 of the waist circumference and waist-to-height ratio among China, Peking and Gansu. Before 15 the data of Gansu were lower than those of China and Beiing;but were higher than that after 16. CONCLUSION: To have constructed percentile normal of waist circumference and waist-to-height ratio for 7-18 children and adolescents in Gansu Province. The study provided a basic data for further studies of child and adolescent central obesity in China.

Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: a potential target for prognosis and immune response.

BACKGROUND: It is critical to understand the mechanisms of human cancers in order to develop the effective anti-cancer therapeutic strategies. Recent studies indicated that primase polymerase (PRIMPOL) is strongly associated with the development of human cancers. Nevertheless, a systematic pan-cancer analysis of PRIMPOL remains to be further clarified. METHOD: Comprehensive multi-omics bioinformatics algorithms, such as TIMER2.0, GEPIA2.0 and cBioPortal, were utilized to evaluate the biological roles of PRIMPOL in pan-cancer, including the expression profiles, genomic alterations, prognostic values and immune regulation. RESULTS: PRIMPOL was upregulated in glioblastoma multiforme and kidney renal clear cell carcinoma. The brain lower grade glioma patients with enhanced PRIMPOL expression displayed poor prognostic values. We also demonstrated the PRIMPOL's immunomodulating effects on pan-cancer as well as its genomic changes and methylation levels. The aberrant expression of PRIMPOL was linked to various cancer-associated pathways, including DNA damage response, DNA repair, and angiogenesis, according to single-cell sequencing and function enrichment. CONCLUSIONS: This pan-cancer analysis offers a thorough review of the functional roles of PRIMPOL in human cancers, suggesting PRIMPOL as a potentially important biomarker for the progression and immunotherapy of various cancers.

Nlrp3 Deficiency Alleviates Lipopolysaccharide-Induced Acute Kidney Injury via Suppressing Renal Inflammation and Ferroptosis in Mice.

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a vital component of many inflammatory responses. Here, we intended to investigate the involvement of NLRP3 in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (S-AKI) and explore its mechanisms. For the first time, we validated elevated NLRP3 expression in the renal tissues of S-AKI patients by immunohistochemistry analysis. Through LPS injection in both wild-type and Nlrp3-/- mice, a S-AKI model was developed. It was found that LPS-induced kidney injury, including an abnormal morphology in a histological examination, abnormal renal function in a laboratory examination, and an increase in the expression of AKI biomarkers, was dramatically reversed in Nlrp3-deficient mice. Nlrp3 deletion alleviated renal inflammation, as evidenced by the suppression of the expression of pro-inflammatory cytokines and chemokines. A combinative analysis of RNA sequencing and the FerrDb V2 database showed that Nlrp3 knockout regulated multiple metabolism pathways and ferroptosis in LPS-induced S-AKI. Further qPCR coupled with Prussian blue staining demonstrated that Nlrp3 knockout inhibited murine renal ferroptosis, indicating a novel mechanism involving S-AKI pathogenesis by NLRP3. Altogether, the aforementioned findings suggest that Nlrp3 deficiency alleviates LPS-induced S-AKI by reducing renal inflammation and ferroptosis. Our data highlight that NLRP3 is a potential therapeutic target for S-AKI.