Three exonic variants in the PHEX gene cause aberrant splicing in a minigene assay.

Background: X-linked hypophosphatemia (XLH, OMIM 307800) is a rare phosphorus metabolism disorder caused by PHEX gene variants. Many variants simply classified as missense or nonsense variants were only analyzed at the DNA level. However, growing evidence indicates that some of these variants may alter pre-mRNA splicing, causing diseases. Therefore, this study aimed to use bioinformatics tools and a minigene assay to ascertain the effects of PHEX variations on pre-mRNA splicing. Methods: We analyzed 174 variants in the PHEX gene described as missense or nonsense variants. Finally, we selected eight candidate variants using bioinformatics tools to evaluate their effects on pre-mRNA splicing using a minigene assay system. The complementary DNA (cDNA) sequence for the PHEX gene (RefSeq NM_000444.6) serves as the basis for DNA variant numbering. Results: Of the eight candidate variants, three were found to cause abnormal splicing. Variants c.617T>G p.(Leu206Trp) and c.621T>A p.(Tyr207*) in exon 5 altered the splicing of pre-mRNA, owing to the activation of a cryptic splice site in exon 5, which produced an aberrant transcript lacking a part of exon 5, whereas variant c.1700G>C p.(Arg567Pro) in exon 16 led to the activation of a cryptic splice site in intron 16, resulting in a partial inclusion of intron 16. Conclusion: Our study employed a minigene system, which has a great degree of flexibility to assess abnormal splicing patterns under the circumstances of patient mRNA samples that are not available, to explore the impact of the exonic variants on pre-mRNA splicing. Based on the aforementioned experimental findings, we demonstrated the importance of analyzing exonic variants at the mRNA level.

Identification of seven variants in the col4a1 gene that alter RNA splicing by minigene assay.

Type IV collagen is an integral component of basement membranes. Mutations in COL4A1, one of the key genes encoding Type IV collagen, can result in a variety of diseases. It is clear that a significant proportion of mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. Here, we analyzed exonic mutations and intronic mutations described in the COL4A1 gene using bioinformatics programs and identified candidate mutations that may alter the normal splicing pattern through a minigene system. We identified seven variants that induce splicing alterations by disrupting normal splice sites, creating new ones, or altering splice regulatory elements. These mutations are predicted to impact protein function. Our results help in the correct molecular characterization of variants in COL4A1 and may help develop more personalized treatment options.

CARD11-BCL10-MALT1 complex-dependent MALT1 activation facilitates myocardial oxidative stress in doxorubicin-treated mice via enhancing k48-linked ubiquitination of Nrf2.

AIMS: Down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffered ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. RESULTS: The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species while decreases in the activities of anti-oxidative enzymes, concomitant with a down-regulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1, and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), and subsequently disrupted the assembly of CARD11, B-cell lymphoma 10 (BCL10) and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. INNOVATION AND CONCLUSION: The E3 ubiquitin ligase function of MALT1 accounts for the down-regulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and subsequent activation of MALT1.

A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Health information in short videos about metabolic dysfunction-associated steatotic liver disease: Analysing quality and reliability.

BACKGROUND & AIMS: Short videos, crucial for disseminating health information on metabolic dysfunction-associated steatotic liver disease (MASLD), lack a clear evaluation of quality and reliability. This study aimed to assess the quality and reliability of MASLD-related videos on Chinese platforms. METHODS: Video samples were collected from three platforms (TikTok, Kwai and Bilibili) during the period from November 2019 to July 2023. Two independent reviewers evaluated the integrity of the information contained therein by scoring six key aspects of its content: definition, epidemiology, risk factors, outcomes, diagnosis and treatment. The quality and reliability of the videos were assessed using the Journal of the American Medical Association (JAMA) criteria, the Global Quality Score (GQS) and the modified DISCERN score. RESULTS: A total of 198 videos were included. The video content exhibited an overall unsatisfactory quality, with a primary emphasis on risk factors and treatment, while diagnosis and epidemiology were seldom addressed. Regarding the sources of the videos, the GQS and modified DISCERN scores varied significantly between the platforms (p = .003), although they had generally similar JAMA scores (p = .251). Videos created by medical professionals differed significantly in terms of JAMA scores (p = .046) compared to those created by nonmedical professionals, but there were no statistically significant differences in GQS (p = .923) or modified DISCERN scores (p = .317). CONCLUSIONS: The overall quality and reliability of the videos were poor and varied between platforms and uploaders. Platforms and healthcare professionals should strive to provide more reliable health-related information regarding MASLD.

Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay.

BACKGROUND: X-linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre-mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype-phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5' end of the exons or internal position of the exons in COL4A5 gene, cause aberrant splicing process. METHODS: We analyzed 401 SNVs previously presumed missense and nonsense variants in COL4A5 gene by bioinformatics programs and identified candidate variants that may affect the splicing of pre-mRNA via minigene assays. RESULTS: Our study indicated three of eight candidate variants induced complete or partial exon skipping. Variants c.2678G>C and c.2918G>A probably disturb classic splice sites leading to corresponding exon skipping. Variant c.3700C>T may disrupt splicing enhancer motifs accompanying with generation of splicing silencer sequences resulting in the skipping of exon 41. CONCLUSION: Our study revealed that two missense variants positioned the first nucleotides of the 5' end of COL4A5 exons and one internal exonic nonsense variant caused aberrant splicing. Importantly, this study emphasized the necessity of assessing the effects of SNVs at the mRNA level.

A novel discrete linkage-type electrode for radiofrequency-induced intestinal anastomosis.

INTRODUCTION: For decades, radiofrequency (RF)-induced tissue fusion has garnered great attention due to its potential to replace sutures and staples for anastomosis of tissue reconstruction. However, the complexities of achieving high bonding strength and reducing excessive thermal damage present substantial limitations of existing fusion devices. MATERIALS AND METHODS: This study proposed a discrete linkage-type electrode to carry out ex vivo RF-induced intestinal anastomosis experiments. The anastomotic strength was examined by burst pressure and shear strength test. The degree of thermal damage was monitored through an infrared thermal imager. And the anastomotic stoma fused by the electrode was further investigated through histopathological and ultrastructural observation. RESULTS: The burst pressure and shear strength of anastomotic tissue can reach 62.2 ± 3.08 mmHg and 8.73 ± 1.11N, respectively, when the pressure, power and duration are 995 kPa, 160 W and 13 s, and the thermal damage can be controlled within limits. Histopathological and ultrastructural observation indicate that an intact and fully fused stomas with collagenic crosslink can be formed. CONCLUSION: The discrete linkage-type electrode presents favorable efficiency and security in RF-induced tissue fusion, and these results are informative to the design of electrosurgical medical devices with controllable pressure and energy delivery.

High efficiency and stable partial nitration achieved via gel immobilization.

Long-term high efficiency and stable partial nitrification (PN) performance was achieved using gel-immobilized partial nitrifying bacteria. The PN characteristics of the filler under high and low ammonia nitrogen concentrations and low temperature were comprehensively studied and the rapid reactivation was achieved after reactor breakdown or long stagnation period. The results showed that the maximum ammonia oxidation rate was 66.8 mg•(L•h)-1 and the nitrite accumulation rate was above 95 % for the filler. Efficient and stable PN performance depends on the high abundance of ammonia-oxidizing bacteria (AOB) inside the filler and dynamically microbial community. In addition, the oxygen-limited zone and competition between the microorganisms inside the filler effectively inhibited the growth of nitrite oxidizing bacteria, and the sludge outside the filler assisted in this process, which supported the dominant position of AOB in fillers. This study provides a reliable technology for the practical application of the PN nitrogen removal process.

Functional analysis of the CTNS gene exonic variants predicted to affect splicing.

Cystinosis is a severe, monogenic systemic disease caused by variants in CTNS gene. Currently, there is growing evidence that exonic variants in many diseases can affect pre-mRNA splicing. The impact of CTNS gene exonic variants on splicing regulation may be underestimated due to the lack of routine studies at the RNA level. Here, we analyzed 59 exonic variants in the CTNS gene using bioinformatics tools and identified candidate variants that may induce splicing alterations by minigene assays. We identified six exonic variants that induce splicing alterations by disrupting the ratio of exonic splicing enhancers/exonic splicing silencers (ESEs/ESSs) or by interfering with the recognition of classical splice sites, or both. Our results help in the correct molecular characterization of variants in cystinosis and inform emerging therapies. Furthermore, our work suggests that the combination of in silico and in vitro assays facilitates to assess the effects of DNA variants driving rare genetic diseases on splicing regulation and will enhance the clinical utility of variant functional annotation.

Optimization of Pedicle Screw Parameters for Enhancing Implant Stability Based on Finite Element Analysis.

OBJECTIVE: To improve implant stability parameters, including pedicle screw (PS) outer diameter, thread depth, and pitch, by finite element analysis. METHODS: Insertion and pullout of the PS were simulated by finite element analysis, and the precision of simulation was evaluated by comparison with mechanical tests. Influences of the parameters on the maximum insertion torque and maximum pullout force were analyzed by computational simulations, including single-factor analysis and orthogonal experiments. RESULTS: The simulation results agreed with the mechanical test results. The order of parameters influencing insertion torque and pullout force was outer diameter > pitch > thread depth. When the pilot hole diameter is 0.1 mm larger than the inner diameter of the PS, the calculated Pearson correlation coefficient between the maximum insertion torque and maximum pullout force was r = 0.99. The optimized PS had a maximum insertion torque of 485.16 N·mm and a maximum pullout force of 1726.33 N, 23.9% and 9.1% higher, respectively, than the values of standard screws. CONCLUSIONS: The presently used models are feasible for evaluating the implant stability of PSs. The maximum insertion torque and maximum pullout force of PSs are highly correlated and can be improved by increasing the outer diameter and decreasing pitch. Although with the parameters of the PS, pedicle size and bone mineral density are 2 additional factors to consider for better implant stability.

Optimizing the hydrolysis-acidification stage in municipal wastewater treatment: comparison of immobilized fillers and granular sludge.

The decomposition of organic macromolecules in sewage currently benefits substantially from hydrolysis-acidification. The full use of its qualities can help domestic sewage to biodegrade more quickly, which promotes the subsequent aerobic reactions. This study evaluated the hydrolysis-acidification performance of granular sludge and filler in residential sewage. Both forms were highly effective at producing volatile fatty acids (VFAs) at the beginning of the reaction, but the granular sludge gradually disintegrated over time, particularly at low temperatures. The production of VFAs decreased (68.08 mg/L), and the effluent dissolved organic nitrogen (DON) increased (6.23 mg/L). However, the effluent of fillers remained at a lower level (1.3 mg/L) and produced more VFAs (74.13 mg/L). High-throughput sequencing revealed that the filler included a greater quantity of hydrolytic-acidifying bacteria than the granular sludge, which resulted in higher performance. In this study, the optimal form of utilizing hydrolytic acidifying bacteria was discussed to provide a theoretical basis to improve the full utilization of organic matter in domestic sewage and the removal of as much total nitrogen as possible.

Inhibition of astroglial hemichannels ameliorates infrasonic noise induced short-term learning and memory impairment.

As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure.

Higher oxidative balance scores are associated with lower nonalcoholic fatty liver disease and not with fibrosis in US adults.

BACKGROUND AND AIMS: Little research have focused on the relationship between systemic oxidative stress status and NAFLD and fibrosis. The Oxidative Balance Score (OBS) is employed to evaluate whole-body lifestyle and diet exposures related to oxidative stress, with higher OBS scores implying exposure to more antioxidants. This study aimed to explore whether OBS is correlated with NAFLD and NAFLD-related fibrosis. METHODS AND RESULTS: 12,223 participants from NHANES 2003-2018 were enrolled in this study. NAFLD was defined as USFLI ≥30 and liver fibrosis was determined as FIB-4 ≥ 2.67. OBS was scored by 20 lifestyle and dietary factors. Weighted logistic regression and restricted cubic splines were used to assess the association between OBS and NAFLD and fibrosis. The prevalence of NAFLD was 29.67%. There was a significant negative correlation between OBS, dietary OBS, lifestyle OBS and NAFLD and no correlation with NAFLD-related fibrosis. Compared to the lowest quartile, the adjusted ORs for the highest quartile of OBS, lifestyle OBS, dietary OBS and NAFLD were 0.55(95%CI:0.35,0.85), 0.12(95%CI:0.08,0.16), 0.70(95%CI:0.52,0.94) respectively. In stratified analyses, lifestyle OBS was negatively associated with NAFLD across gender, dietary OBS was only negatively correlated with NAFLD in men, and any OBS was not observed to be relevant to NAFLD-related fibrosis. CONCLUSIONS: OBS was negatively associated with NAFLD, but not with NAFLD-related fibrosis. The findings underline the significance of adhering to an antioxidant lifestyle and diet, which can help prevent NAFLD but seems to be ineffective in preventing fibrosis in individuals with NAFLD.

Non-retroareolar male mucinous breast cancer without gynecomastia development in an elderly man: A case report.

BACKGROUND: Male breast cancer (MBC) is an extremely rare condition and accounts for less than 1% of all breast cancers, and malignant tumors occur in less than 1% of the affected men. Mucinous breast cancer is extremely rare and accounts for 2% of all invasive breast cancers. Generally, MBC is accompanied by a retroareolar mass. CASE SUMMARY: Herein, we report a case of male mucinous breast carcinoma (MMBC) without gynecomastia development and with mass localization outside the common retroareolar region, wherein the mass was a painless nodule in the right breast of a 64-year-old man. We also discuss the clinical and pathological characteristics of this unusual tumor. The excised breast specimen showed pure mucinous carcinoma. The patient had strong expression of estrogen and progesterone receptors, a low Ki-67 proliferation index of the tumor cells, and negative pathological axillary lymph nodes. The patient underwent modified radical mastectomy and axillary lymph node dissection, followed by tamoxifen hormone therapy. CONCLUSION: To the best of our knowledge, this is the first case report of MMBC in the non-retroareolar region of the nipple without gynecomastia development. Mucinous tumors are easily missed during diagnosis, and the incidence of axillary lymph node metastases of chest mucinous tumors has increased.

Viral infections inhibit saponin biosynthesis and photosynthesis in Panax notoginseng.

Virus-infected Panax notoginseng plants with chlorotic, mosaic, and pitted leaves are ubiquitous in the primary P. notoginseng-producing region in Wenshan autonomous prefecture, Yunnan province, China. However, the viruses that infect P. notoginseng and the effects of viral infections on the biosynthesis of secondary metabolites and photosynthesis remain unknown. This study identified a variety of viruses infecting P. notoginseng plants via deep-sequencing of small RNA (sRNA). Of the 10 identified viruses, seven had not previously been detected in P. notoginseng, including Cauliflower mosaic virus and Soybean chlorotic mottle virus. In addition, the simultaneous infection of P. notoginseng by Panax notoginseng virus A (PnVA), Panax cryptic virus 4 (PCV4), and Tomato yellow leaf curl China virus (TYLCCNV) was confirmed by PCR. Moreover, a quantitative PCR analysis showed that the expression levels of key genes related to saponin biosynthesis were generally down-regulated in the virus-infected P. notoginseng. Additionally, high-performance liquid chromatography results indicated the saponin content decreased in the roots of virus-infected P. notoginseng plants. The activities of photosynthesis-related enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose 1,6-bisphosphatase, and fructose 1,6-biphosphate aldolase, decreased significantly in the virus-infected P. notoginseng plants. The viral infections also induced the expression of antioxidant genes and increased antioxidant enzyme activities. Furthermore, the expression levels of many resistance-related genes were up-regulated in P. notoginseng plants inoculated with a viral suspension. The study results provide the foundation for future research on P. notoginseng viral diseases, which may lead to the development of enhanced disease control measures.

Limited Impact of Soil Microorganisms on the Endophytic Bacteria of Tartary Buckwheat (Fagopyrum tataricum).

Soil has been considered the main microbial reservoir for plants, but the robustness of the plant microbiome when the soil resource is removed has not been greatly considered. In the present study, we tested the robustness of the microbiota recruited by Tartary buckwheat (Fagopyrum tataricum Gaertn.), grown on sterile humus soil and irrigated with sterile water. Our results showed that the microbiomes of the leaf, stem, root and next-generation seeds were comparable between treated (grown in sterile soil) and control plants (grown in non-sterile soil), indicating that the plants had alternative robust ways to shape their microbiome. Seed microbiota contributed greatly to endophyte communities in the phyllosphere, rhizosphere and next-generation seeds. The microbiome originated from the seeds conferred clear benefits to seedling growth because seedling height and the number of leaves were significantly increased when grown in sterilized soil. The overall microbiome of the plant was affected very little by the removal of the soil microbial resource. The microbial co-occurrence network exhibited more interactions, and Proteobacteria was enriched in the root of Tartary buckwheat planted in sterilized soil. Our research broadens the understanding of the general principles governing microbiome assembly and is widely applicable to both microbiome modeling and sustainable agriculture.

Identified eleven exon variants in PKD1 and PKD2 genes that altered RNA splicing by minigene assay.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic multisystem disease caused primarily by mutations in the PKD1 gene or PKD2 gene. There is increasing evidence that some of these variants, which are described as missense, synonymous or nonsense mutations in the literature or databases, may be deleterious by affecting the pre-mRNA splicing process. RESULTS: This study aimed to determine the effect of these PKD1 and PKD2 variants on exon splicing combined with predictive bioinformatics tools and minigene assay. As a result, among the 19 candidate single nucleotide alterations, 11 variants distributed in PKD1 (c.7866C > A, c.7960A > G, c.7979A > T, c.7987C > T, c.11248C > G, c.11251C > T, c.11257C > G, c.11257C > T, c.11346C > T, and c.11393C > G) and PKD2 (c.1480G > T) were identified to result in exon skipping. CONCLUSIONS: We confirmed that 11 variants in the gene of PKD1 and PKD2 affect normal splicing by interfering the recognition of classical splicing sites or by disrupting exon splicing enhancers and generating exon splicing silencers. This is the most comprehensive study to date on pre-mRNA splicing of exonic variants in ADPKD-associated disease-causing genes in consideration of the increasing number of identified variants in PKD1 and PKD2 gene in recent years. These results emphasize the significance of assessing the effect of exon single nucleotide variants in ADPKD at the mRNA level.

Seismic Behavior Analysis of Recycled Aggregate Concrete-Filled Square Steel Tube Frames.

In this study, the seismic behavior of a recycled aggregate concrete-filled square steel tube (S-RACFST) frame under different design conditions was investigated. Based on previous studies, a finite element model for the seismic behavior of the S-RACFST frame was developed. Moreover, the axial compression ratio, beam-column line stiffness ratio, and yield bending moment ratio of the beam-column were regarded as the variation parameters. It was through these parameters that the seismic behavior of eight S-RACFST frame finite element specimens was discussed. The seismic behavior indexes, such as the hysteretic curve, ductility coefficient, energy dissipation coefficient, and stiffness degradation were obtained-which, in turn, revealed the influence law and the degree of the design parameters regarding seismic behavior. Moreover, the sensitivity of the various parameters with respect to the seismic behavior of the S-RACFST frame was evaluated via grey correlation analysis. The results show that the hysteretic curves of the specimens were fusiform and full with respect to the different parameters. Firstly, with the axial compression ratio increasing from 0.2 to 0.4, the ductility coefficient increased by 28.5%. In addition, the equivalent viscous damping coefficient of the specimen with the axial compression ratio of 0.4 was 17.9% higher than that of the specimen with the axial compression ratio of 0.2, which was 11.5% as well as that with an axial compression ratio of 0.3. Second, when the line stiffness ratio rises from 0.31 to 0.41, the specimens' bearing capacity and displacement ductility coefficient both get better. However, the displacement ductility coefficient gradually decreases when the line stiffness ratio is greater than 0.41. As a result, an optimal line stiffness ratio (0.41) thus exhibits good energy dissipation capacity. Thirdly, with the increase in the yield bending moment ratio from 0.10 to 0.31, the bearing capacity of the specimens improves. In addition, the positive and negative peak loads increased by 16.4% and 22.8%, respectively. Moreover, the ductility coefficients were all close to three, thus demonstrating good seismic behavior. The stiffness curve of the specimen with a large yield bending moment ratio with respect to the beam-column, is higher than those that possess a small beam-column yield moment ratio. In addition, the yield bending moment ratio of the beam-column possesses a significant influence on the seismic behavior of the S-RACFST frame. Furthermore, the yield bending moment ratio of the beam-column should be considered first in order to ensure the seismic behavior of the S-RACFST frame.

Association between depression and oxidative balance score: National Health and Nutrition Examination Survey (NHANES) 2005-2018.

BACKGROUND: Few studies have investigated the relationship between systemic oxidative stress status and depression. The oxidative balance score (OBS) was used to assess systemic oxidative stress status, with higher OBS scores implying exposure to more antioxidants. This study aimed to explore whether OBS is associated with depression. METHODS: 18,761 subjects from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were selected. Depression was diagnosed by the Patient Health Questionnaire (PHQ-9, score ≥ 10). OBS was scored by 20 dietary and lifestyle factors. Weighted logistic regression and restricted cubic splines (RCS) were used to assess the association between OBS and depression. RESULTS: The prevalence of depression was 8.42 %. There was a significant negative nonlinear relationship between OBS, dietary OBS, lifestyle OBS and depression (p for nonlinear < 0.05). Compared to the lowest quartile of OBS, the adjusted ORs for the highest quartile of OBS, dietary OBS, and lifestyle OBS and depression were 0.290 (95 % CI: 0.193-0.434), 0.500(95 % CI: 0.380-0.658), 0.403(95 % CI: 0.299-0.545) respectively, and all P for trend < 0.001. In stratified analyses, three OBS were negatively associated with the odds of depression across sex groups (all P for trend < 0.05), and the OR was smaller in the female group than in the male group. LIMITATIONS: Cross-sectional data and absence of drug considerations. CONCLUSIONS: OBS was strongly negatively associated with depression, especially in females. The findings underline the significance of adhering to an antioxidant diet and lifestyle, which helps prevent depression and appears to be of greater benefit to women.

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Necroptosis is one of the regulated cell death, which involves receptor interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain like protein (MLKL) signaling pathway. Among them, MLKL is the final execution of necroptosis. The formation of RIPK1/RIPK3/MLKL necrosome induces the phosphorylated MLKL, and the activated MLKL penetrates into the membrane bilayer to form membrane pores, which damages the integrity of the membrane and leads to cell death. In addition to participating in necroptosis, MLKL is also closely related to other cell death, such as NETosis, pyroptosis, and autophagy. Therefore, MLKL is involved in the pathological processes of various diseases related to abnormal cell death pathways (such as cardiovascular diseases, neurodegenerative diseases and cancer), and may be a therapeutic target of multiple diseases. Understanding the role of MLKL in different cell death can lay a foundation for seeking various MLKL-related disease targets, and also guide the development and application of MLKL inhibitors.