Regioselective Synthesis of α-Quaternary Amino Acid Derivatives Enabled by Photoinduced Energy Transfer.

α-Quaternary amino acids have found application in many biologically relevant compounds and pharmaceuticals. Although there are many methods for the synthesis of α-quaternary amino acids, most of them are mainly realized with the aid of transition metals and complex ligands. We present herein a 2,7-Br-4CzIPN catalyzed regioselective alkylation of azlactones with redox-active esters via radical-radical couplings. Strikingly, this approach is devoid of any metal or additive and shows broad scope and superior sensitive functional group compatibility.

Sirtuin 6 protects against podocyte injury by blocking the renin-angiotensin system by inhibiting the Wnt1/ß-catenin pathway.

Sirtuins (Sirts) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases that share diverse cellular functions. Increasing evidence shows that Sirts play a critical role in podocyte injury, which is a major determinant of proteinuria-associated renal disease. Membranous nephropathy (MN) is a typical glomerular disease in which podocyte damage mediates proteinuria development. In this study we investigated the molecular mechanisms underlying the regulatory roles of Sirt in podocyte injury in MN patients, rats with cationic bovine serum albumin (CBSA)-induced MN and zymosan activation serum (ZAS)-stimulated podocytes. Compared with healthy controls, MN patients showed significant reduction in intrarenal Sirt1 and Sirt6 protein expression. In CBSA-induced MN rats, significant reduction in intrarenal Sirt1, Sirt3 and Sirt6 protein expression was observed. However, only significant decrease in Sirt6 protein expression was found in ZAS-stimulated podocytes. MN patients showed significantly upregulated protein expression of Wnt1 and ß-catenin and renin-angiotensin system (RAS) components in glomeruli. CBSA-induced MN rats exhibited significantly upregulated protein expression of intrarenal Wnt1 and ß-catenin and their downstream gene products as well as RAS components. Similar results were observed in ZAS-stimulated podocytes. In ZAS-stimulated podocytes, treatment with a specific Sirt6 activator UBCS039 preserved the protein expression of podocin, nephrin and podocalyxin, accompanied by significant inhibition of the protein expression of ß-catenin and its downstream gene products, including Snail1 and Twist; treatment with a ß-catenin inhibitor ICG-001 significantly preserved the expression of podocyte-specific proteins and inhibited the upregulation of downstream ß-catenin gene products accompanied by significant suppression of the protein expression of RAS components. Thus, we demonstrate that Sirt6 ameliorates podocyte injury by blocking RAS signalling via the Wnt1/ß-catenin pathway. Sirt6 is a specific therapeutic target for the treatment of podocyte damage-associated renal disease.

Integrative phosphatidylcholine metabolism through phospholipase A2 in rats with chronic kidney disease.

Dysregulation in lipid metabolism is the leading cause of chronic kidney disease (CKD) and also the important risk factors for high morbidity and mortality. Although lipid abnormalities were identified in CKD, integral metabolic pathways for specific individual lipid species remain to be clarified. We conducted ultra-high-performance liquid chromatography-high-definition mass spectrometry-based lipidomics and identified plasma lipid species and therapeutic effects of Rheum officinale in CKD rats. Adenine-induced CKD rats were administered Rheum officinale. Urine, blood and kidney tissues were collected for analyses. We showed that exogenous adenine consumption led to declining kidney function in rats. Compared with control rats, a panel of differential plasma lipid species in CKD rats was identified in both positive and negative ion modes. Among the 50 lipid species, phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC) and lysophosphatidic acid (LysoPA) accounted for the largest number of identified metabolites. We revealed that six PCs had integral metabolic pathways, in which PC was hydrolysed into LysoPC, and then converted to LysoPA, which was associated with increased cytosolic phospholipase A2 protein expression in CKD rats. The lower levels of six PCs and their corresponding metabolites could discriminate CKD rats from control rats. Receiver operating characteristic curves showed that each individual lipid species had high values of area under curve, sensitivity and specificity. Administration of Rheum officinale significantly improved impaired kidney function and aberrant PC metabolism in CKD rats. Taken together, this study demonstrates that CKD leads to PC metabolism disorders and that the dysregulation of PC metabolism is involved in CKD pathology.

Intrarenal 1-methoxypyrene, an aryl hydrocarbon receptor agonist, mediates progressive tubulointerstitial fibrosis in mice.

Recent studies have shown that endogenous metabolites act via aryl hydrocarbon receptor (AhR) signalling pathway in tubulointerstitial fibrosis (TIF) pathogenesis. However, the mechanisms underlying endogenous metabolite-mediated AhR activation are poorly characterised. In this study, we conducted untargeted metabolomics analysis to identify the significantly altered intrarenal metabolites in a mouse model of unilateral ureteral obstruction (UUO). We found that the levels of the metabolite 1-methoxypyrene (MP) and the mRNA expression of AhR and its target genes CYP1A1, CYP1A2, CYP1B1 and COX-2 were progressively increased in the obstructed kidney at Weeks 1, 2 and 3. Furthermore, these changes were positively correlated with progressive TIF in UUO mice. In NRK-52E, RAW 264.7 and NRK-49F cells, MP dose-dependently upregulated the mRNA expression of AhR and its four target genes and the protein expression of nuclear AhR, accompanied by the upregulated protein expression of collagen I, α-SMA and fibronectin, as well as downregulated E-cadherin expression. Consistently, oral administration of MP in mice progressively enhanced AhR activity and upregulated profibrotic protein expression in the kidneys; these effects were partially inhibited by AhR knockdown in MP-treated mice and cell lines. In addition, we screened and identified erythro-guaiacylglycerol-ß-ferulic acid ether (GFA), which was isolated from Semen plantaginis, as a new AhR antagonist. GFA significantly attenuated TIF in MP-treated NRK-52E cells and mice by partially antagonising AhR activity. Our results suggest that MP activates AhR signalling, thus mediating TIF through epithelial-mesenchymal transition and macrophage-myofibroblast transition. MP is a crucial metabolite that contributes to TIF via AhR signalling pathway.

[Differences in non-suicidal self-injury behaviors between only-child and non-only-child adolescents with mood disorders: a cross-sectional study]. / ç‹¬ç”Ÿä¸Žéžç‹¬ç”Ÿé’å°‘å¹´æƒ ç»ªéšœç¢æ‚£è€ éžè‡ªæ€æ€§è‡ªä¼¤è¡Œä¸ºå·®å¼‚çš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the differences in non-suicidal self-injury (NSSI) behaviors between only-child and non-only-child adolescents with mood disorders. METHODS: A three-stage sampling method was used to perform a cross-sectional survey of 529 adolescents, aged 12-18 years, who had mood disorders and NSSI behaviors. These adolescents were sampled from the outpatient service of 20 mental hospitals in 9 provinces of China from August to November 2020. A self-made questionnaire was used to collect general demographic data. The Functional Assessment of Self-Mutilation, Beck Scale for Suicide Ideation, Kessler Psychological Distress Scale, Stress Mindset Measure-General, Multidimensional Scale of Perceived Social Support, Multidimensional Students' Life Satisfaction Scales, and Rosenberg Self-Esteem Scale were used to collect the information on self-injury behaviors and psychological factors in these adolescents. RESULTS: A total of 529 adolescents with mood disorders and NSSI behaviors were surveyed, among whom 375 were only-child adolescents and 154 were non-only-child adolescents. Compared with the non-only-child group, the only-child group had a significantly higher total score of Functional Assessment of Self-Mutilation (P<0.05) .The type and frequency of self-injury in the only-child group were significantly higher than those in the non-only-child group (P<0.05). Psychological analysis showed that compared with the non-only-child group, the only-child group had a significantly lower score of self-esteem (P<0.05) and significantly higher scores of psychological distress and depressive symptoms (P<0.05). The multiple linear regression analysis showed that the score of suicidal ideation was positively correlated with the frequency of NSSI behaviors in both only-child and non-only-child adolescents with mood disorders (P<0.05); in the only-child adolescents, the level of self-esteem was negatively correlated with the frequency of NSSI behaviors (P<0.05), and the score of stress perception was positively correlated with the frequency of NSSI behaviors (P<0.05); in the non-only-child adolescents, the score of anxious emotion was positively correlated with the frequency of NSSI behaviors (P<0.05). CONCLUSIONS: Among the adolescents with mood disorders and NSSI behaviors, the only-child adolescents tend to have a higher frequency of self-injury and poorer mental health, and therefore, the only-child adolescents with mood disorders and NSSI behaviors need more attention.

Deciphering the cellular mechanisms underlying fibrosis-associated diseases and therapeutic avenues.

Fibrosis is the excessive deposition of extracellular matrix components, which results in disruption of tissue architecture and loss of organ function. Fibrosis leads to high morbidity and mortality worldwide, mainly due to the lack of effective therapeutic strategies against fibrosis. It is generally accepted that fibrosis occurs during an aberrant wound healing process and shares a common pathogenesis across different organs such as the heart, liver, kidney, and lung. A better understanding of the fibrosis-related cellular and molecular mechanisms will be helpful for development of targeted drug therapies. Extensive studies revealed that numerous mediators contributed to fibrogenesis, suggesting that targeting these mediators may be an effective therapeutic strategy for antifibrosis. In this review, we describe a number of mediators involved in tissue fibrosis, including aryl hydrocarbon receptor, Yes-associated protein, cannabinoid receptors, angiopoietin-like protein 2, high mobility group box 1, angiotensin-converting enzyme 2, sphingosine 1-phosphate receptor-1, SH2 domain-containing phosphatase-2, and long non-coding RNAs, with the goal that drugs targeting these important mediators might exhibit a beneficial effect on antifibrosis. In addition, these mediators show profibrotic effects on multiple tissues, suggesting that targeting these mediators will exert antifibrotic effects on different organs. Furthermore, we present a variety of compounds that exhibit therapeutic effects against fibrosis. This review suggests therapeutic avenues for targeting organ fibrosis and concurrently identifies challenges and opportunities for designing new therapeutic strategies against fibrosis.

Metabolomics in renal cell carcinoma: From biomarker identification to pathomechanism insights.

Renal cell carcinoma (RCC) is a frequently diagnosed cancer with high prevalence, which is inversely associated with survival benefit. Although myriad studies have shed light on disease causality, unfortunately, thus far, RCC diagnosis is faced with numerous obstacles partly due to the insufficient knowledge of effective biomarkers, hinting deeper mechanistic understanding are urgently needed. Metabolites are recognized as final proxies for gene-environment interactions and physiological homeostasis as they reflect dynamic processes that are ongoing or have been taken place, and metabolomics may therefore offer a far more productive and cost-effective route to disease discovery, particularly within the arena for new biomarker identification. In this review, we primarily expatiate recent advances in metabolomics that may be amenable to novel biomarkers or therapeutic targets for RCC, which may expand our armaments to win more bettles against RCC.

Cardiac rupture complicating acute myocardial infarction: the clinical features from an observational study and animal experiment.

BACKGROUND: Cardiac rupture (CR) is a fatal complication of ST-elevation myocardial infarction (STEMI) with its incidence markedly declined in the recent decades. However, clinical features of CR patients now and the effect of reperfusion therapy to CR remain unclear. We investigated the clinical features of CR in STEMI patients and the effect of reperfusion therapy to CR in mice. METHODS: Two studies were conducted. In clinical study, data of 1456 STEMI patients admitted to the First Hospital, Xi'an Jiaotong University during 2015.12. ~ 2018.12. were analyzed. In experimental study, 83 male C57BL/6 mice were operated to induce MI. Of them, 39 mice were permanent MI (group-1), and remaining mice received reperfusion after 1 h ischemia (21 mice, group-2) or 4 h ischemia (23 mice, group-3). All operated mice were monitored up to day-10. Animals were inspected three times daily for the incidence of death and autopsy was done for all mice found died to determine the cause of death. RESULTS: CR was diagnosed in 40 patients: free-wall rupture in 17, ventricular septal rupture in 20, and combined locations in 3 cases. CR presented in 19 patients at admission and diagnosed in another 21 patients during 1 ~ 14 days post-STEMI, giving an in-hospital incidence of 1.4%. The mortality of CR patients was high during hospitalization accounting for 39% of total in-hospital death. By multivariate logistic regression analysis, older age, peak CK-MB and peak hs-CRP were independent predictors of CR post-STEMI. In mice with non-reperfused MI, 17 animals (43.6%) died of CR that occurred during 3-6 days post-MI. In MI mice received early or delayed reperfusion, all mice survived to the end of experiment except one mouse died of acute heart failure. CONCLUSION: CR remains as a major cause of in-hospital death in STEMI patients. CR patients are characterized of being elderly, having larger infarct and more server inflammation. Experimentally, reperfusion post-MI prevented CR.

Correction to: Cardiac rupture complicating acute myocardial infarction: the clinical features from an observational study and animal experiment.

An amendment to this paper has been published and can be accessed via the original article.

IgG4-related disease: association between chronic rhino-sinusitis and systemic symptoms.

PURPOSE: The objective of this study is to analyze the relationship between chronic rhino-sinusitis (CRS) and systemic symptoms in patients with IgG4-related disease (IgG4-RD). PATIENTS AND METHODS: The patients with IgG4-RD, confirmed by restrict association with clinical and histopathological manifestations between March 2013 and July 2016, were enrolled and followed-up for 1 year at the Tongren Hospital, Capital Medical University. The patients were divided into two groups: the case group included IgG4-RD patients with CRS confirmed by clinical and imaging, while the control group included IgG4-RD patients without CRS confirmed by clinical and imaging. Age, gender, clinical manifestations, the percentage of eosinophils in peripheral blood, sedimentation (ESR), C-reaction protein, serum IgE and IgG4 levels, histopathology, and treatment drugs at the baseline and 1 year of follow-up were compared between the two groups. RESULTS: A total of 46 cases met the diagnostic criteria for IgG4-RD. A total of 30 patients (65.2%) had IgG4-RD complicated with CRS, and were aged 49.7 ± 13.4 years, with male:female ratio = 2:1. The disease duration in the case group was longer than that in the control group (3.0 versus 0.8, p = 0.009). The ratio of ocular involvement was higher (86.7 versus 60%, p < 0.001), and allergic manifestations including drug allergy, asthma, and allergic skin were more common (56.5 versus 20%, p = 0.004), with a higher percentage of eosinophils in peripheral blood (8.5 versus 3.3%, p = 0.018) and more sensitive to glucocorticoids (6.0 versus 3.5, p = 0.004) than those in the control group. CONCLUSIONS: CRS in patients with IgG4-RD was closely associated with IgG4-related ocular lesions, which was more prone to allergic manifestations accompanied by raised percentage of eosinophils in peripheral blood. The treatment of patients with IgG4-RD complicated with CRS was more effective than those with IgG4-RD without CRS.

[Effects of family cohesion and adaptability on behavioral problems in preschool children].

OBJECTIVE: To investigate the effects of family cohesion and adaptability on behavioral problems in preschool children. METHODS: The stratified cluster multistage sampling method was used to perform a questionnaire survey in the parents of 1 284 children aged 3-6 years in the urban area of Lanzhou, China. The general status questionnaire, Conners Child Behavior Checklist (Parent Symptom Question), and Family Adaptability and Cohesion Scale, Second edition, Chinese version (FACESII-CV) were used to investigate behavioral problems and family cohesion and adaptability. RESULTS: The overall detection rate of behavioral problems in preschool children was 17.13%. The children with different types of family cohesion had different detection rates of behavioral problems, and those with free-type family cohesion showed the highest detection rate of behavioral problems (40.2%). The children with different types of family adaptability also had different detection rates of behavioral problems, and those with stiffness type showed the highest detection rate of behavioral problems (25.1%). The behavioral problems in preschool children were negatively correlated with family cohesion and adaptability. CONCLUSIONS: During the growth of preschool children, family cohesion and adaptability have certain effects on the mental development of preschool children.

Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites.

BACKGROUND AND PURPOSE: Membranous nephropathy (MN) is an immune-mediated glomerular disease in adults. Antibody- and antigen-bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition-mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis. EXPERIMENTAL APPROACH: In this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)-induced MN rats and in patients with idiopathic MN (IMN). KEY RESULTS: Impaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan-produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole-3-pyruvic acid, indole-3-aldehyde and tryptamine and negatively correlated with increased levels of indole-3-lactic acid and indole-3-acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down-regulated cytoplasmic AhR, but up-regulated nuclear AhR, in MN rats and IMN patients. CONCLUSION AND IMPLICATIONS: Activation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors.

Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.

Arachidonic acid (AA) is a main component of cell membrane lipids. AA is mainly metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). Esterified AA is hydrolysed by phospholipase A2 into a free form that is further metabolized by COX, LOX and CYP450 to a wide range of bioactive mediators, including prostaglandins, lipoxins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. Increased mitochondrial oxidative stress is considered to be a central mechanism in the pathophysiology of the kidney. Along with increased oxidative stress, apoptosis, inflammation and tissue fibrosis drive the progressive loss of kidney function, affecting the glomerular filtration barrier and the tubulointerstitium. Recent studies have shown that AA and its active derivative eicosanoids play important roles in the regulation of physiological kidney function and the pathogenesis of kidney disease. These factors are potentially novel biomarkers, especially in the context of their involvement in inflammatory processes and oxidative stress. In this review, we introduce the three main metabolic pathways of AA and discuss the molecular mechanisms by which these pathways affect the progression of acute kidney injury (AKI), diabetic nephropathy (DN) and renal cell carcinoma (RCC). This review may provide new therapeutic targets for the identification of AKI to CKD continuum.

Electrical injuries in children-a 6-year retrospective study.

BACKGROUND: This study aimed to assess the clinical epidemiological characteristics of children with electrical injuries and discuss the countermeasures for the prevention of electrical injuries in children. METHODS: The children with electrical injuries were grouped according to whether or not they were admitted to the hospital for treatment into inpatient and outpatient groups. Clinical data such as gender, causes of injury and injury-causing voltage distribution in different age groups were analyzed. The factors affecting hospitalization were subjected to χ2 test, Kruskal-Wallis H test, and logistic regression analysis. RESULTS: A total of 321 children were included with 37 divided into inpatient group and 284 divided into outpatient group. The incidence of electrical injuries was highest in children ≤6 years old and in the summer. There were significantly different in gender, place of occurrence, cause of injury and injury-causing voltage between the two groups (p < 0.05). Injury-causing voltage is an independent risk factor affecting hospitalization of children with electrical injuries (OR = 0.116, 95 %CI = 0.040-0.334, p = 0.000). In children ≤6 years old, boys suffered electrical injuries more frequently than girls; battery powered vehicle (47.53 %) was primarily the cause of injury; most of the patients (64.64 %) were exposed to low voltage below 100 Vs, mainly in the case of adolescent children. CONCLUSION: Male preschoolers accounted for the majority of electrical injury cases, and these accidents mostly happened in household electrical appliances and household battery cars. Overall, it is necessary to improve family electrical safety education and reinforce protective measures against electric injury to children.

A Deep-Learning Model for Diagnosing Fresh Vertebral Fractures on Magnetic Resonance Images.

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.

Decoding nitric oxide release rates of amine-based diazeniumdiolates.

Amine-based diazeniumdiolates (NONOates) have garnered widespread use as nitric oxide (NO) donors, and their potential for nitroxyl (HNO) release has more recently been realized. While NO release rates can vary significantly with the type of amine, half-lives of seconds to days under physiological conditions, there is as yet no way to determine a priori the NO or HNO production rates of a given species, and no discernible trends have manifested other than that secondary amines produce only NO (i.e., no HNO). As a step to understanding these complex systems, here we describe a procedure for modeling amine-based NONOates in water solvent that provides an excellent correlation (R(2) = 0.94) between experimentally measured dissociation rates of seven secondary amine species and their computed NO release activation energies. The significant difference in behavior of NONOates in the gas and solvent phases is also rigorously demonstrated via explicit additions of quantum mechanical water molecules. The presented results suggest that the as-yet unsynthesized simplest amine-based NONOate, the diazeniumdiolated ammonia anion [H2N-N(O)═NO(-)], could serve as an unperturbed HNO donor. These results provide a step forward toward the accurate modeling of general NO and/or HNO donors as well as for the identification of tailored prodrug candidates.

TGF-ß as A Master Regulator of Aging-Associated Tissue Fibrosis.

Fibrosis is the abnormal accumulation of extracellular matrix proteins such as collagen and fibronectin. Aging, injury, infections, and inflammation can cause different types of tissue fibrosis. Numerous clinical investigations have shown a correlation between the degree of liver and pulmonary fibrosis in patients and telomere length and mitochondrial DNA content, both of which are signs of aging. Aging involves the gradual loss of tissue function over time, which results in the loss of homeostasis and, ultimately, an organism's fitness. A major feature of aging is the accumulation of senescent cells. Senescent cells abnormally and continuously accumulate in the late stages of life, contributing to age-related fibrosis and tissue deterioration, among other aging characteristics. Furthermore, aging generates chronic inflammation, which results in fibrosis and decreases organ function. This finding suggests that fibrosis and aging are closely related. The transforming growth factor-beta (TGF-ß) superfamily plays a crucial role in the physiological and pathological processes of aging, immune regulation, atherosclerosis, and tissue fibrosis. In this review, the functions of TGF-ß in normal organs, aging, and fibrotic tissues is discussed: TGF-ß signalling is altered with age and is an indicator of pathology associated with tissue fibrosis. In addition, this review discusses the potential targeting of noncoding.

[Emission Inventory of Airborne Pollutants from Biomass Combustion in Guizhou Province].

With the objective to ascertain the emissions of biomass combustion in Guizhou, the activity levels were measured through data collection and field surveys, and the emission factors were acquired using actual monitoring data and data cited from previous literature. A 3 km×3 km-gridded emission inventory of nine air pollutants from biomass combustion sources in Guizhou Province in 2019 was developed in combination with GIS technology. The results showed that the total emissions of CO, NOx, SO2, NH3, VOCs, PM2.5, PM10, BC, and OC in Guizhou were estimated to be 293505.53, 14781.19, 4146.11, 8501.07, 45025.70, 39463.58, 41879.31, 6832.33, and 15134.74 t, respectively. The distribution of atmospheric pollutants emitted by biomass combustion sources in different cities was noticeably uneven, being mainly concentrated in Qiandongnan Miao and Dong Autonomous Prefecture. The analysis of variation characteristics of emissions indicated that the monthly emissions were concentrated in February, March, April, and December, and the hourly emissions peaked daily from 14:00 to 15:00. Some uncertainty remained in the emission inventory. It is necessary to perform in-depth analyses of the accuracy of obtaining activity-level data, localize the emission factors through more combustion experiments in subsequent research for improving the emission inventory of air pollutants from biomass combustion in Guizhou Province, and provide a basis for the cooperative governance of the atmospheric environment.

Oxidative stress and inflammation are mediated via aryl hydrocarbon receptor signalling in idiopathic membranous nephropathy.

Membranous nephropathy (MN) patients are diagnosed by the presence of phospholipase A2 receptor (PLA2R) before they progress to renal failure. However, the subepithelium-like immunocomplex deposit-mediated downstream molecular pathways are poorly understood. The aryl hydrocarbon receptor (AHR), NF-ƙB and Nrf2 pathways play central roles in the pathogenesis and progression of chronic kidney disease. However, their mutual effects on MN require further examination. Thus, we investigated the effect of AHR signalling on the NF-ƙB and Nrf2 pathways in IMN patients, cationic bovine serum albumin (CBSA)-injected rats and zymosan activation serum (ZAS)-treated podocytes. IMN patients show significantly decreased serum total protein and albumin levels, increased urine protein levels and intrarenal IgG4 and PLA2R protein expression in glomeruli compared with controls. IMN patients exhibited increased mRNA expression of intrarenal AHR and its target genes, including CYP1A1, CYP1A2, CYP1B1 and COX-2. This increase was accompanied by significantly upregulated protein expression of CD3, NF-ƙB p65 and COX-2 and significantly downregulated Nrf2 and HO-1 expression. Similarly, CBSA-induced rats showed severe proteinuria and activated intrarenal AHR signalling. This was accompanied by significantly upregulated protein expression of intrarenal p-IκBα, NF-κB p65 and its gene products, including COX-2, MCP-1, iNOS, 12-LOX, p47phox and p67phox, and significantly downregulated protein expression of Nrf2 and its gene products, including HO-1, catalase, GCLC, GCLM, MnSOD and NQO1. These results were further verified in ZAS-induced podocytes. Treatment with the AHR antagonist CH223191 and AHRsiRNA significantly preserved podocyte-specific protein expression and improved the NF-ƙB and Nrf2 pathways in ZAS-induced podocytes. In contrast, similar results were obtained in ZAS-induced podocytes treated with the NF-ƙB inhibitor BAY 11-7082 and NF-κBp65 siRNA. However, neither method had a significant effect on AHR signalling. Collectively, these results indicate that the NF-ƙB pathway is a downstream target of AHR signalling. Our findings suggest that blocking AHR signalling inhibits oxidative stress and inflammation, thereby improving proteinuria and renal injury.

Biomechanical effects of screws of different materials on vertebra-pediculoplasty: a finite element study.

Background: The effects of cannulated screws made of polyetheretherketone (PEEK) on the biomechanical properties of the vertebral body during vertebra-pediculoplasty remain unclear. This study aimed to investigate whether PEEK screws have the potential to replace titanium alloy screws. Methods: The surgical model of two different materials of screws was constructed using the finite element method. The biomechanical effects of the two models on the vertebral body under different working conditions were compared. Results: ① The peak von Mises stress of PEEK screws was significantly lower than that of titanium screws, with a reduction ranging from 52% to 80%. ② The von Mises stress values for the injured T12 spine were similar for both materials. Additionally, the segmental range of motion and intervertebral disc pressure showed no significant difference between the two materials. Conclusion: PEEK screws demonstrated advantages over titanium screws and may serve as a viable alternative for screw materials in vertebra-pediculoplasty.