Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology: A Prospective Cohort Study.

BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China. METHODS: This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time. RESULTS: Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00-6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15-9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014). CONCLUSIONS: Higher sdLDL-C was associated with an increased risk of incident carotid plaques, especially carotid plaques with vulnerable morphology, even in participants with normal LDL-C. This suggests the potential of sdLDL-C as a therapeutic target for stroke prevention. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017197.

Remission of organ failure in patients with predicted severe acute pancreatitis treated by somatostation, octreotide and cyclooxygenase-2 inhibitors.

BACKGROUND: /Objectives: Persistent organ failure (OF) in severe acute pancreatitis (SAP) is caused by activation of cytokine cascades, resulting in inflammatory injury. Anti-inflammation may be helpful in OF remission in early SAP. To assess the efficacy of anti-inflammatory regimens for OF prevention and remission in patients with predicted SAP and display clinical doctors' acceptance of these strategies, we conducted this retrospective study in the real world. METHODS: Clinical data of patients with predicted SAP from 2010 to 2017 were retrospectively reviewed. Cases were divided into conventional support (C), C+ somatostatin/octreotide (C + S/O), and C + S/O + Cyclooxygenase-2-inhibitors (C + S/O + COX-2-I). The occurrence of SAP, OF, changes of proportion for three strategies, length of hospital stay, meperidine injection, and cytokine levels were compared. The constituent ratios of the three schemes over eight years were evaluated. RESULTS: A total of 580 cases (C = 124, C + S/O = 290, C + S/O + COX-2-I = 166) were included. The occurrences of SAP in the C + S/O (28.3 %) and C + S/O + COX-2-I (18.1 %) groups were significantly lower than that in C group (60.5 %, P < 0.001), mainly by reducing persistent respiratory failure (P < 0.001) and renal failure (P = 0.002). C + S/O and C + S/O + COX-2-I regimens significantly decreased new onset OF and enhanced OF amelioration within 48 h when compared with C treatment (P < 0.001) in patients with OF score <2 and ≥ 2 on admission, respectively. C + S/O and C + S/O + COX-2-I as compared with C group significantly decrease OF occurrences in a multivariate logistic regression analysis (P < 0.05). CONCLUSIONS: Somatostatin or its analogs and cyclooxygenase-2 inhibitors are promising for OF prevention and remission in patients with predicted SAP. The acceptance of combined strategies in the real world has increased, and the occurrence of SAP has decreased annually.

Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods.

OBJECTIVES: The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing with liquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. METHODS: Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. RESULTS: All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (-14.4 to -3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (-8.3 to -2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (-18.3 to -3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (-17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. CONCLUSIONS: The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Mapping trends in hemifacial spasm research: bibliometric and visualization-based analyses of the Web of Science Core Collection.

Hemifacial spasm (HFS) is a common cranial nerve disease. In HFS research, we conducted a bibliometric analysis to examine the development and research trends. A retrieval of HFS studies published between 2011 and 2022 was performed from the Web of Science Core Collection in September 2022. Two scientometric tools were used to perform bibliometric and visualization-based analyses: VOSviewer and CiteSpace. Bibliometric analysis of 1461 studies published between 2011 and 2022 was carried out using data from 444 journals, 6021 authors, 1732 institutions, and 76 countries/regions. China, the USA, Japan, and South Korea were four key contributors to this study. Shanghai Jiaotong University was the major institution with the larger number of publications. Li Shiting was the most prolific author. Jannetta PJ was the most co-cited author. World Neurosurgery was the top prolific journal. Journal of Neurosurgery was the top co-cited journal. The top five keywords were hemifacial spasm, microvascular decompression, trigeminal neuralgia, surgery, and neurovascular compression. This study examines the research trends in global scientific research on HFS over the last decade. Researchers interested in learning more about current trends and novel research frontiers in this area can benefit from the study.

Brain magnetic resonance imaging findings in children with neurological complications of coronavirus disease 2019 (Omicron variant): a multicenter retrospective observational study.

BACKGROUND: An increasing rate of encephalopathy associated with coronavirus disease 2019 (COVID-19) has been observed among children. However, the literature on neuroimaging data in children with COVID-19 is limited. OBJECTIVE: To analyze brain magnetic resonance imaging (MRI) of pediatric COVID-19 patients with neurological complications. MATERIALS AND METHODS: This multicenter retrospective observational study analyzed clinical (n=102, 100%) and neuroimaging (n=93, 91.2%) data of 102 children with COVID-19 infections and comorbid acute neurological symptoms. These children were hospitalized at five pediatric intensive care units (PICUs) in China between December 1, 2022, and January 31, 2023. RESULTS: All patients were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as detected via reverse transcriptase polymerase chain reaction. About 75.7% of the children were infected with the Omicron variant BF.7 strain. Brain MRI was performed 1-12 days following the onset of neurological symptoms, which revealed acute neuroimaging findings in 74.2% (69/93) of cases, including evidence of acute necrotizing encephalopathy (33/69, 47.8%), encephalitis (31/69, 44.9%), reversible splenial lesion syndrome (3/69, 4.3%), reversible posterior leukoencephalopathy (1/69, 1.4%), and hippocampal atrophy (1/69, 1.4%). CONCLUSIONS: Overall, these data highlighted five neuroimaging patterns associated with the outbreak of the SARS-CoV-2 Omicron variant, with acute necrotizing encephalopathy being the most common of these neuroimaging findings. Rarely, the brain MRI of these pediatric COVID-19 patients also demonstrate hippocampal atrophy.

Supervisor Undermining, Social Isolation and Subordinates' Problematic Drinking: The Role of Depression and Perceived Drinking Norms.

Findings regarding the mechanism underlying the impact of supervisor incivility on subordinate alcohol misuse remain equivocal. Specifically, some studies indicate that stress mediates the impact of supervisor incivility on subordinate alcohol misuse, while others, find no evidence for such an effect, suggesting the need to investigate other mechanisms. Extending Conservation of Resource (COR) theory and employing a longitudinal study design, this study examines two alternative mechanisms grounded on social isolation. The first suggests drinking as a resource-mobilizing response, with social isolation eliciting the perception of more permissive injunctive drinking norms, thus facilitating problematic drinking. The second suggests problematic drinking as a mode of coping with a negative emotional state elicited by social isolation, namely depression. Findings indicate that supervisor undermining's association with subsequent subordinate problematic drinking is serially mediated by social isolation and depression, with no support found for the first mechanism. Implications for research, practice and policy are discussed.

Changes in family situation and concurrent changes in working life: a 15-year longitudinal analysis.

OBJECTIVE: Currently, little is known regarding changes in family situation with concurrent changes in working life. This study aimed to examine whether changes in family situation (based on living with children and/or marrying/divorcing) were associated with changes in working life and whether the associations were influenced by sex, genetics and early life environment. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Data from Swedish national registers of 16 410 twins were used. Fixed-effects logistic regression models assessing ORs with 95% CIs were applied to examine associations between changes in family situation and working life controlling for time-invariant effects and adjusted for covariates, and conditional models to account for confounding of genetics and early life environment. RESULTS: Changes in individuals life situation from being single and living without children to married and living with children were associated with transitioning from unsustainable (ie, having unemployment or sickness absence/disability pension) to sustainable working life (men: OR 2.40, 95% CI 2.26 to 2.56; women: OR 1.68, 95% CI 1.59 to 1.78). Changes from being married to single, in contrast, attenuated the likelihood of transitioning to a sustainable working life. Moreover, changes in men's working life seem to be more dependent on changes in family situation compared with women. Genetic factors and early life environment play a role in the associations. CONCLUSIONS: Family formation increases the likelihood of a more stable working life whereas divorce is a risk factor for work interruptions. Our study emphasises that family formation improves the work life situation and to a higher degree for men.

Identification of Ossnrk1a-1 Regulated Genes Associated with Rice Immunity and Seed Set.

Sucrose non-fermenting-1-related protein kinase-1 (SnRK1) is a highly conserved serine-threonine kinase complex regulating plants' energy metabolisms and resistance to various types of stresses. However, the downstream genes regulated by SnRK1 in these plant physiological processes still need to be explored. In this study, we found that the knockout of OsSnRK1a resulted in no obvious defects in rice growth but notably decreased the seed setting rate. The ossnrk1a mutants were more sensitive to blast fungus (Magnaporthe oryzae) infection and showed compromised immune responses. Transcriptome analyses revealed that SnRK1a was an important intermediate in the energy metabolism and response to biotic stress. Further investigation confirmed that the transcription levels of OsNADH-GOGAT2, which positively controls rice yield, and the defense-related gene pathogenesis-related protein 1b (OsPR1b) were remarkably decreased in the ossnrk1a mutant. Moreover, we found that OsSnRK1a directly interacted with the regulatory subunits OsSnRK1ß1 and OsSnRK1ß3, which responded specifically to blast fungus infection and starvation stresses, respectively. Taken together, our findings provide an insight into the mechanism of OsSnRK1a, which forms a complex with specific ß subunits, contributing to rice seed set and resistance by regulating the transcription of related genes.

The efficacy and safety of tacrolimus in treating refractory IgA vasculitis nephritis: a single-center retrospective study on 16 cases.

Background: This study aimed to observe the efficacy and safety of tacrolimus in the treatment of refractory immunoglobulin A vasculitis nephritis (IgAVN). Methods: Sixteen patients with IgAVN who had been previously treated with cyclophosphamide shock therapy at least five times, some of whom had also received mycophenolate but still had persistent proteinuria, were enrolled. The clinical and pathological data were collected and analysed. Results: The average (mean ± standard deviation) age at the initial assessment for the group of 16 patients was 10 ± 2.7 years. Finally, at the end of their respective follow-up time point, 6 of the 16 patients achieved complete remission (37.5%), 5 achieved partial remission (31.2%), and 5 had no remission (31.2%). A significant difference was found in the median proteinuria before and after a 6-month course of tacrolimus treatment [19.2 (11.2, 31.9) vs 7.8 (4.3, 13.9) mg/kg/day] (P < .05). During the first 6 months of tacrolimus treatment, all patients' estimated glomerular filtration rate levels remained normal. The mean tacrolimus blood concentration was 6.0 ± 2.6 ng/mL. The median prednisone dosage was decreased from 10 mg/day to 5 mg/day, and prednisone was eventually stopped in three individuals. No drug-related adverse effects were observed during treatment. Conclusions: Tacrolimus has demonstrated efficacy in increasing remission rates, significantly lowering urinary protein levels, and reducing steroid use in children with refractory IgAVN. Further research is required to investigate its optimal blood concentrations, long-term effects and renoprotective properties.

Integrating carbon and water footprint into nature-based solution (NBS) for urban planning in a highly built-up area in Guangzhou, China.

Stormwater management problems have been deteriorated with the high frequency and intensity of precipitation owing to rapid urbanization and climate variability, especially in urban highly built-up area. Nature-based solutions (NBS) have emerged as a powerful measure for rising these challenges due to their ability to mitigate urban waterlogging and increase carbon sequestration. Identifying optimal locations for NBS implementation remains a critical research focus. This study integrates carbon and water footprint accounting into NBS-based planning for sustainable urban development in central Guangzhou, China, to enhance urban flooding mitigation and carbon sequestration. Through carbon-water footprint analysis and weighting, we prioritized NBS planning. To achieve the objectives of increasing sequestered carbon and reducing urban runoff, three types of NBS-green roofs, permeable pavements, and bioretention systems-were optimized for a high-priority town street. The results showed that the implementation of green roof and permeable pavement reduced the surface runoff by 3.58 %, while the biological retention system reduced the runoff gray water by 27 %. Moreover, the application of green roof and biological retention increased the carbon sequestration by 2.57 million kg CO2-eq (life cycle). The findings of this study provide comprehensive insights into optimization of NBS planning based on carbon-water footprint accounting, facilitating to enhance mitigation of urban flooding vulnerability and carbon sequestration.

Does voice endorsement by supervisors enhance or constrain voicer's personal initiative? Countervailing effects via feeling pride and feeling envied.

While the previous research has examined antecedents of supervisors' voice endorsement, it has generally overlooked its effects on voicers' affective and behavioral reactions, probably because of the underlying assumption that supervisors' voice endorsement is inherently beneficial and likely to encourage more proactive behaviors in the future. In this research, we offer a theoretical model of the double-edged effects of supervisors' voice endorsement on voicers' subsequent personal initiative. Drawing on cognitive appraisal theory and related research, we proposed that supervisors' voice endorsement prompts two different cognitive appraisal processes in voicers that evoke two distinct emotional experiences-feeling pride and feeling envied-with countervailing effects on voicers' subsequent personal initiative. Specifically, voice endorsement results in voicers not only feeling pride, which enhances their subsequent personal initiative, but also in their feeling envied, which reduces their later personal initiative. Moreover, we extend the cognitive appraisal theory of emotion from a social constructionist approach by incorporating coworker support-an important relational context-as a contingent factor shaping the effects of voice endorsement on feeling pride and feeling envied and on voicers' subsequent personal initiative. The results from two field studies-a weekly experience sampling study with 574 observations from 119 employees and an event-based daily experience sampling study with 787 observations from 180 employees-largely support our theoretical model. This research suggests the importance of considering the perspectives of all the stakeholders in the proactivity triad (i.e., the focal employee, the supervisor, and coworkers) in order to sustain employee proactivity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Antitumor Effect of Platinum-Modified STING Agonist MSA-2.

The stimulator of interferon genes (STING)-activated innate immune pathway is strong and durable for tumor immunotherapy. MSA-2 is an available non-nucleotide human STING agonist that promotes the tumor immunotherapy of STING activation. However, strategies for remolding and improving the immunotherapy effects of MSA-2 are of value for clinical applications. Here, we synthesized the platinum salt-modified MSA-2 (MSA-2-Pt) due to platinum salt being a classic chemotherapeutic drug. We found that MSA-2-Pt could achieve double-effect antitumor immunotherapy, including inducing cell death by platinum and activating the STING pathway by MSA-2. In the colon carcinoma MC38 model (sensitive to immune checkpoint immunotherapy tumor) and melanoma B16F10 model (poorly immunogenic and highly aggressive tumor), the MSA-2-Pt had a good antitumor effect, which was a little better than MSA-2 with intratumor injections. The results present a promising strategy for STING activation in tumor immunotherapy and broadening platinum-based drugs.

Peptide-drug conjugates: A new paradigm for targeted cancer therapy.

Peptide-drug conjugates (PDCs) are the new hope for targeted therapy after antibody-drug conjugates (ADCs). Compared with ADCs, the core advantages of PDCs are enhanced tissue penetration, easier chemical synthesis, and lower production costs. Two PDCs have been approved by the US Food and Drug Administration (FDA) for the treatment of cancer. The therapeutic effects of PDCs are remarkable, but PDCs also encounter problems when used as targeted therapeutics, such as poor stability, a short blood circulation time, a long research and development time frame, and a slow clinical development process. Therefore, it is very urgent and important to understand the latest research progress of cancer cells targeting PDC, the solution to its stability problem, the scheme of computer technology to assist its research and development, and the direction of its future development. In this manuscript, based on the structure and function of PDCs, the latest research progress on PDCs from the aspects of cancer cell-targeting peptide (CTP) selection, pharmacokinetic characteristics, stability regulation and so on were systematically reviewed, hoping to highlight the current problems and future development directions of PDCs.

Phosphorylation of Mad1 at serine 18 by Mps1 is required for the full virulence of rice blast fungus, Magnaporthe oryzae.

The spindle assembly checkpoint (SAC) proteins are conserved among eukaryotes safeguarding chromosome segregation fidelity during mitosis. However, their biological functions in plant-pathogenic fungi remain largely unknown. In this study, we found that the SAC protein MoMad1 in rice blast fungus (Magnaporthe oryzae) localizes on the nuclear envelope and is dispensable for M. oryzae vegetative growth and tolerance to microtubule depolymerizing agent treatment. MoMad1 plays an important role in M. oryzae infection-related development and pathogenicity. The monopolar spindle 1 homologue in M. oryzae (MoMps1) interacts with MoMad1 through its N-terminal domain and phosphorylates MoMad1 at Ser-18, which is conserved within the extended N termini of Mad1s from fungal plant pathogens. This phosphorylation is required for maintaining MoMad1 protein abundance and M. oryzae full virulence. Similar to the deletion of MoMad1, treatment with Mps1-IN-1 (an Mps1 inhibitor) caused compromised appressorium formation and decreased M. oryzae virulence, and these defects were dependent on its attenuating MoMad1 Ser-18 phosphorylation. Therefore, our study indicates the function of Mad1 in rice blast fungal pathogenicity and sheds light on the potential of blocking Mad1 phosphorylation by Mps1 to control crop fungal diseases.

Adaptation process of decellularized vascular grafts as hemodialysis access in vivo.

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

Understanding the global subnational migration patterns driven by hydrological intrusion exposure.

Amid the escalating global climatic challenges, hydrological risks significantly influence human settlement patterns, underscoring the imperative for an in-depth comprehension of hydrological change's ramifications on human migration. However, predominant research has been circumscribed to the national level. The study delves into the nonlinear effects of hydrological risks on migration dynamics in 46,776 global subnational units. Meanwhile, leveraging remote sensing, we procured globally consistent metrics of hydrological intrusion exposure, offering a holistic risk assessment encompassing hazard, exposure, and vulnerability dimensions, thus complementing previous work. Here, we show that exposure is the primary migration driver, surpassing socioeconomic factors. Surrounding disparities further intensified exposure's impact. Vulnerable groups, especially the economically disadvantaged and elderly, tend to remain in high-risk areas, with the former predominantly migrating within proximate vicinities. The nonlinear analysis delineates an S-shaped trajectory for hydrological exposure, transitioning from resistance to migration and culminating in entrapment, revealing dependence on settlement resilience and adaptability.

Expansion and contraction of lake basin shape the genetic structure of Sinocyclocheilus (Osteichthyes: Cypriniformes: Cyprinidae) populations in Central Yunnan, China.

Geological events can strongly affect the genetic structures and differentiation of fish populations. Especially, as an endemic fish of the genus Sinocyclocheilus in the Yunnan-Guizhou Plateau, the effects of key geological events on the distributions and genetic structures remain poorly understood. Examining the phylogeographic patterns of Sinocyclocheilus fishes can be useful for elucidating the spatio-temporal dynamics of their population size, dispersal history and extent of geographical isolation, thereby providing a theoretical basis for their protection. Here, we used single nucleotide polymorphisms (SNP) method to investigate the phylogeographic patterns of Sinocyclocheilus fishes. Our analysis supports the endemicity of Sinocyclocheilus, but the samples of different regions of Sinocyclocheilus contain multiple ancestral components, which displayed more admixed and diversified genetic components, this may be due to the polymorphism of the ancestors themselves, or gene infiltration caused by hybridization between adjacent species of Sinocyclocheilus. We estimate that the most recent common ancestor (MRCA) of Sinocyclocheilus fish in the Central Yunnan Basin at approximately 3.75~3.11 Ma, and infer that the evolution of Sinocyclocheilus in the central Yunnan Basin is closely related to the formation of plateau lakes (around 4.0~0.02 Ma), and identifies the formation of Dianchi Lake and Fuxian Lake as key geological events shaping Sinocyclocheilus population structure. It is also the first time to prove that the altitude change has a great influence on the genetic variation among the populations of Sinocyclocheilus.

Immune-Related Genes and Immune Cell Infiltration Characterize the Maturation Status of Arteriovenous Fistulas: An Integrative Bioinformatics Study and Experimental Validation Based on Transcriptome Sequencing.

Purpose: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but the low maturation rate is concerning. Immune cells' impact on AVF maturation lacks bioinformatics research. The study aims to investigate the potential predictive role of immune-related genes and immune cell infiltration characteristics in AVF maturation. Patients and Methods: We analyzed the high-throughput sequencing dataset to identify differentially expressed genes (DEGs). Then, we performed enrichment analyses (GO, KEGG, GSEA) on immune-related genes and pathways in mature AVF. We focused on differentially expressed immune-related genes (DEIRGs) and constructed a PPI network to identify hub genes. These hub genes were validated in other databases and experiments, including qPCR and immunohistochemistry (IHC). The immune cell infiltration characteristics in native veins, failed AVFs, and matured AVFs were analyzed by cibersortX. Partial experimental validation was conducted using clinical samples. Results: Our results showed that immune-related genes and signaling pathways are significantly enriched in mature AVF. We validated this in other databases and ultimately identified three hub genes (IL1B, IL6, CXCR4) in combination with experiments. Significant differences in immune cell infiltration characteristics were observed among native veins, failed AVFs, and matured AVFs. Immune cell infiltration analysis revealed that accumulation of CD4+ T cells, dendritic cells, mast cells and M2 macrophages contribute to AVF maturation. These immune-related genes and immune cells have the potential to serve as predictive factors for AVF maturation. We partially validated this experimentally. Conclusion: From a bioinformatics perspective, our results have identified, for the first time, a set of immune-related genes and immune cell infiltration features that can characterize the maturation of AVF and significantly impact AVF maturation. These features hold potential as predictive indicators for AVF maturation outcomes.