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Ophiothrix (Ophiothrix) exigua is a common brittle star in the northwestern Pacific. As a dominant species, O. exigua inhabiting the intertidal rocky ecosystem are affected by multiple environmental stressors, but molecular insights into their genetic population structure remain poorly studied. In this study, we investigated the population genetics and evolutionary history of six O. exigua populations from the northern China Sea using mitochondrial (COI, NAD4) and nuclear (ITS2, 18S) gene markers. High haplotype diversity, low nucleotide diversity, and low rates of gene differentiation among the populations of O. exigua were detected. Pairwise genetic differentiation (ΦST) statistics between different localities were negative or low and insignificant, suggesting strong gene flow of this species over the study areas. The phylogenetic analyses showed that the populations exhibited high homogeneity between localities in our study area. Demographic analyses indicated that the populations experienced sustained expansion around 0.2 million years ago. This expansion was likely related to transgressions events in the Yellow Sea during the Pleistocene period. Additional samples of O. exigua from disparate geographical locations, especially the Japan Sea and the Korean Peninsula, will be needed to unravel the population genetic patterns and evolutionary history of this species.

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Acute myeloid leukemia (AML), as the most common malignancy of the hematopoietic system, poses challenges in treatment efficacy, relapse, and drug resistance. In this study, we have utilized 151 RNA sequencing datasets, 194 DNA methylation datasets, and 200 somatic mutation datasets from the AML cohort in the TCGA database to develop a multi-omics stratification model. This model enables comparison of prognosis, clinical features, gene mutations, immune microenvironment and drug sensitivity across subgroups. External validation datasets have been sourced from the GEO database, which includes 562 mRNA datasets and 136 miRNA datasets from 984 adult AML patients. Through multi-omics-based stratification model, we classified 126 AML patients into 4 clusters (CS). CS4 had the best prognosis, with the youngest age, highest M3 subtype proportion, fewest copy number alterations, and common mutations in WT1, FLT3, and KIT genes. It showed sensitivity to HDAC inhibitors and BCL-2 inhibitors. Both the M3 subtype and CS4 were identified as independent protective factors for survival. Conversely, CS3 had the worst prognosis due to older age, high copy number alterations, and frequent mutations in RUNX1, DNMT3A, and TP53 genes. Additionally, it showed higher proportions of cytotoxic cells and Tregs, suggesting potential sensitivity to mTOR inhibitors. CS1 had a better prognosis than CS2, with more copy number alterations, while CS2 had higher monocyte proportions. CS1 showed good sensitivity to cytarabine, while CS2 was sensitive to RXR agonists. Both CS1 and CS2, which predominantly featured mutations in FLT3, NPM1, and DNMT3A genes, benefited from FLT3 inhibitors. Using the Kappa test, our stratification model underwent robust validation in the miRNA and mRNA external validation datasets. With advancements in sequencing technology and machine learning algorithms, AML is poised to transition towards multi-omics precision medicine in the future. We aspire for our study to offer new perspectives on multi-drug combination clinical trials and multi-targeted precision medicine for AML.

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Bismuth oxybromide (BiOBr) nanomaterials are well-known efficient powder-shaped photocatalyst for degrading antibiotic wastewater, but their practical applications have been limited by unsatisfactory photo-absorption, weak photocatalytic activity and poor recyclability. To address these issues, we demonstrate that the growing of S-doped BiOBr nanosheets on carbon fiber cloth (CFC) can lead to efficient photocatalysis with recyclable features. With carbon fiber cloth as the substrate, S-doped BiOBr (BiOBr-Sx) nanosheets (diameter: ∼500 nm, thicknesses: ∼5-90 nm) was prepared by solvothermal method with thiourea as dopant. With the increase of thiourea (0-0.2 g) in the precursor solution, BiOBr-Sx nanosheets exhibit a significant shift in the photo-absorption edge from 420 to 461 nm and decreased thicknesses from 90 to 5 nm, accompanying by the increased proportion of (010) exposed surface. Amony them, CFC/BiOBr-S0.5 can degrade various contaminants (such as 98.7 % levofloxacin (LVFX), 95.6 % ciprofloxacin (CIP) and 95.9 % tetracycline (TC)) with most degradation efficiency within 120 min of visible light irradiation, which are 1.6, 1.9 and 1.4 times than that of CFC/BiOBr (61.4 % LVFX, 49.5 % CIP and 67.1 % TC), respectively. Significantly, when CFC/BiOBr-S0.05 photocatalytic fabric is combined with a multi-stage flow device to treat the flowing wastewater (10 mg/L LVFX, rate: 1 L/h), 91.0 % LVFX can be degraded after tenth grade. Therefore, this study not only demonstrates the controllable preparation of S-doped BiOBr nanosheets with different thickness on CFC but also highlights the practical applications of fabric-based photocatalysts for purifying the flowing sewage efficiently.

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Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.

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BACKGROUND: The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. OBJECTIVE: A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. METHODS: A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. RESULTS: A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. CONCLUSION: Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

ANTECEDENTES: O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. OBJETIVO: Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. MéTODOS: Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. RESULTADOS: Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. CONCLUSãO: Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.

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There is a close relationship between preconception health and maternal and child health outcomes, and the consequences may be passed down from generation to generation. In 2018, Lancet published three consecutive articles emphasizing the importance of the preconception period. Phthalic acid ester (PAE) exposure during this period may affect gametogenesis and epigenetic information in gametophytes, thereby affecting embryonic development and offspring health. Therefore, this article reviews the effects of parental preconception PAE exposure on reproductive/birth outcomes and offspring health, to provide new evidence on this topic. We searched Web of Science, MEDLINE (through PubMed), the China National Knowledge Infrastructure (CNKI), ScienceDirect, and the VIP Journal Library from the date of database establishment to July 3, 2024. Finally, 12 articles were included. Three studies investigated the health hazards (effects on birth weight, abortion, etc.) of women's preconception PAE exposure. Nine studies involved both parents. Nine studies considered the impacts of PAE preconception exposure on reproductive/birth outcomes, focusing on birth weight, pregnancy loss, preterm birth, embryo quality, and placental weight. Three studies considered the impacts of preconception PAE exposure on offspring behavior. The results of this review suggested that parental preconception PAE exposure may have an impact on reproductive/birth outcomes and offspring behavior, including birth weight, child behavior, and dietary behavior. However, studies on the health hazards of preconception PAE exposure are relatively scarce, and the outcomes of current studies are varied. It is necessary to use systematic reviews to verify an accurate research question to provide recommendations for public health policy making.

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A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems. Recently, we established a mouse papillomavirus (MmuPV1) model that is relevant to HPV genital pathogenesis. In the current study, we validated the use of Papanicolaou (Pap) smears, a valuable early diagnostic tool for detecting HPV cervical cancer, to monitor disease progression in the MmuPV1 mouse model. Biweekly cervicovaginal swabs were collected from the MmuPV1-infected mice for viral DNA quantitation and cytology assessment. The Pap smear slides were evaluated for signs of epithelial cell abnormalities using the 2014 Bethesda system criteria. Tissues from the infected mice were harvested at various times post-viral infection for additional histological and virological assays. Over time, increased viral replication was consistent with higher levels of viral DNA, and it coincided with an uptick in epithelial cell abnormalities with higher severity scores noted as early as 10 weeks after viral infection. The cytological results also correlated with the histological evaluation of tissues harvested simultaneously. Both immunocompromised and immunocompetent mice with squamous cell carcinoma (SCC) cytology also developed vaginal SCCs. Notably, samples from the MmuPV1-infected mice exhibited similar cellular abnormalities compared to the corresponding human samples at similar disease stages. Hence, Pap smear screening proves to be an effective tool for the longitudinal monitoring of disease progression in the MmuPV1 mouse model. IMPORTANCE: Papanicolaou (Pap) smear has saved millions of women's lives as a valuable early screening tool for detecting human papillomavirus (HPV) cervical precancers and cancer. However, more than 200,000 women in the United States alone remain at risk for cervical cancer due to pre-existing HPV infection-induced precancers, as there are currently no effective treatments for HPV-associated precancers and cancers other than invasive procedures including a loop electrosurgical excision procedure (LEEP) to remove abnormal tissues. In the current study, we validated the use of Pap smears to monitor disease progression in our recently established mouse papillomavirus model. To the best of our knowledge, this is the first study that provides compelling evidence of applying Pap smears from cervicovaginal swabs to monitor disease progression in mice. This HPV-relevant cytology assay will enable us to develop and test novel antiviral and anti-tumor therapies using this model to eliminate HPV-associated diseases and cancers.

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Mangroves perform a crucial ecological role along the tropical and subtropical coastal intertidal zone where salinity fluctuation occurs frequently. However, the differential responses of mangrove plant at the combined transcriptome and metabolome level to variable salinity are not well documented. In this study, we used Avicennia marina (Forssk.) Vierh., a pioneer species of mangrove wetlands and one of the most salt-tolerant mangroves, to investigate the differential salt tolerance mechanisms under low and high salinity using inductively coupled plasma-mass spectrometry, transcriptomic and metabolomic analysis. The results showed that HAK8 was up-regulated and transported K+ into the roots under low salinity. However, under high salinity, AKT1 and NHX2 were strongly induced, which indicated the transport of K+ and Na+ compartmentalization to maintain ion homeostasis. In addition, A. marina tolerates low salinity by up-regulating ABA signaling pathway and accumulating more mannitol, unsaturated fatty acids, amino acids' and L-ascorbic acid in the roots. Under high salinity, A. marina undergoes a more drastic metabolic network rearrangement in the roots, such as more L-ascorbic acid and oxiglutatione were up-regulated, while carbohydrates, lipids and amino acids were down-regulated in the roots, and, finally, glycolysis and TCA cycle were promoted to provide more energy to improve salt tolerance. Our findings suggest that the major salt tolerance traits in A. marina can be attributed to complex regulatory and signaling mechanisms, and show significant differences between low and high salinity.

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Copper-based catalysts exhibit high activity in electrochemical CO2 conversion to value-added chemicals. However, achieving precise control over catalysts design to generate narrowly distributed products remains challenging. Herein, a gallium (Ga) liquid metal-based approach is employed to synthesize hierarchical nanoporous copper (HNP Cu) catalysts with tailored ligament/pore and crystallite sizes. The nanoporosity and polycrystallinity are generated by dealloying intermetallic CuGa2 formed after immersing pristine Cu foil in liquid Ga in a basic or acidic solution. The liquid metal-based approach allows for the transformation of monocrystalline Cu to the polycrystalline HNP Cu with enhanced CO2 reduction reaction (CO2RR) performance. The dealloyed HNP Cu catalyst with suitable crystallite size (22.8 nm) and nanoporous structure (ligament/pore size of 45 nm) exhibits a high Faradaic efficiency of 91% toward formate production under an applied potential as low as -0.3 VRHE. The superior CO2RR performance can be ascribed to the enlarged electrochemical catalytic surface area, the generation of preferred Cu facets, and the rich grain boundaries by polycrystallinity. This work demonstrates the potential of liquid metal-based synthesis for improving catalysts performance based on structural design, without increasing compositional complexity.

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Metabolic reprogramming is frequently accompanied by hepatocellular carcinoma (HCC) progression. Disrupted metabolites act as potential biomarkers and drug therapeutic targets for HCC. Peptide extract of scorpion venom (PESV) induces cytotoxic anti-proliferative effects and apoptosis in tumors. However, the action mechanisms of PESV remain unknown. This study aimed to explore the serum metabolic profiles of tumor-bearing mouse model. We generated an orthotopic HCC xenograft mouse model by implanting H22 cells into the left hepatic lobe of male C57BL/6 mice. After surgery, the mice were assigned to two groups randomly: PESV (PESV-treated 40 mg/kg daily, i.g.; n = 6) and control (treated with the solvent equally for 14 d, n = 6) groups. Based on an untargeted metabolomics approach using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry, differential metabolites were screened via univariate and multivariate data analyses. A total of 48 differential metabolites in negative ion mode and 63 in positive ion mode were identified in the serum samples. Furthermore, metabolic pathway analysis revealed that aminoacyl-tRNA biosynthesis, amino acid pathway, glutathione metabolism, protein transports, protein digestion and absorption, and cAMP signaling pathways play vital roles in PESV-induced inhibition of tumors. These findings highlight the distinct changes in the metabolic profiles of HCC-bearing mice after PESV treatment, suggesting the potential of the identified metabolic molecules as therapeutic targets for HCC.

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Healthy, nutritious, and delicious mulberry wine is loved by everyone, but there is no specific yeast for mulberry wine. To screen for yeasts with low-yield higher alcohols for the fermentation of mulberry wine, we tested five commonly used commercial yeasts available on the market to ferment mulberry wine. All five yeasts were able to meet the requirements in terms of yeast fermentation capacity, speed, and physical and chemical markers of mulberry wine. The national standards were met by the fermentation requirements and the fermented mulberry wine. We identified yeast DV10 as a yeast with low-yield higher alcohols suitable for mulberry wine fermentation. The total higher alcohol content in fermented mulberry wine was 298 mg/L, which was 41.9% lower than that of fermented mulberry wine with yeast EC118. The contents of 17 free amino acids and five sugars in mulberry juice and five yeast-fermented mulberry wines were tested. The results showed that the higher the amino acid and sugar content in yeast-fermented mulberry wine, the higher the content of higher alcohols produced by fermentation. A correlation analysis performed on each higher alcohol produced when yeast DV10 fermented the mulberry wine indicated decreased sugar and related amino acids. The findings demonstrated a substantial negative correlation among the levels of increased alcohol, decreased sugar, and matching amino acid content. Considering the correlation values among increased alcohol, decreased sugar, and related amino acids, the very slight difference suggests that both sugar anabolism and amino acid catabolism pathways have an equivalent impact on the synthesis of higher alcohols during the fermentation of mulberry wine. These results provide a theoretical basis for reducing the content of higher alcohols in mulberry wines, given the history and foundation for producing mulberry wine.

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Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

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Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

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Human chorionic gonadotropin (HCG), a vital protein for pregnancy determination and a marker for trophoblastic diseases, finds application in monitoring early pregnancy and ectopic pregnancy. This study presents an innovative approach employing electrochemical immunosensors for enhanced HCG detection, utilizing Anti-HCG antibodies and gold nanoparticles (AuNPs) in the sensor platform. Two sensor configurations were optimized: BSA/Anti-HCG/c-AuNPs/MEL/e-AuNPs/SPCE with [Fe(CN)6]3-/4- as a redox probe (1) and BSA/Anti-HCG/PPy/e-AuNPs/SPCE using polypyrrole (PPy) as a redox probe (2). The first sensor offers linear correlation in the 0.10-500.00 pg∙mL-1 HCG range, with a limit of detection (LOD) of 0.06 pg∙mL-1, sensitivity of 32.25 µA∙pg-1∙mL∙cm-2, RSD <2.47 %, and a recovery rate of 101.03-104.81 %. The second sensor widens the HCG detection range (40.00 fg∙mL-1-5.00 pg∙mL-1) with a LOD of 16.53 fg∙mL-1, ensuring precision (RSD <1.04 %) and a recovery range of 94.61-106.07 % in serum samples. These electrochemical immunosensors have transformative potential in biomarker detection, offering enhanced sensitivity, selectivity, and stability for advanced healthcare diagnostics.

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Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

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Background: To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk. Methods: By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results. Results: Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility. Conclusion: In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.

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The cold-water species Ophiura sarsii, a brittle star, is a key echinoderm in the Arctic continental shelf region, highly sensitive to climate change. However, the absence of a high-quality genome has hindered a thorough understanding of its adaptive evolution. In this study, we reported the first chromosome-level genome assembly of O. sarsii. The genome assembly totalled 1.57 Gb, encompassing 19 chromosomes with a GC content of 37.11% and a scaffold N50 length of 78.03 Mb. The Benchmarking Universal Single-Copy Orthologs (BUSCO) assessment yielded a completeness estimate of 93.5% for this assembly. We predicted a total of 27,099 protein-coding genes, with 25,079 functionally annotated. The genome was comprised of 58.09% transposable elements. This chromosome-level genome of O. sarsii contributes to our understanding of the origin and evolution of marine organisms.

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OBJECTIVE: There has been some confusion in earlier research on the connection between thyroid function and polycystic ovary syndrome (PCOS). This research is aimed to probe into the correlation between thyroid condition and the risk of PCOS from a new standpoint of thyroid hormone sensitivity. METHODS: This research comprised 415 females with PCOS from Drum Tower Hospital Affiliated with the Medical School of Nanjing University, and 137 non-PCOS individuals were selected as the normal control. Based on free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH), we calculated the thyroid hormone sensitivity indices, which consist of Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), Thyrotroph Thyroxine Resistance Index (TT4RI) and Free Triiodothyronine /Free thyroxine (FT3/FT4). The binary logistic regression model was adopted to investigate the correlation between thyroid hormone sensitivity indices with the risk of PCOS. Pearson or Spearman correlation analysis was employed to explore the association among thyroid-related measures with metabolic parameters in PCOS. RESULTS: Results of this research showed that females with PCOS had rising TFQI, TSHI, TT4RI, and FT3/FT4 levels compared with the control group. After adjustment for the impact of various covariates, there was no significant correlation between FT3/FT4 and the risk of PCOS; However, the odds ratio of the third and fourth vs. the first quartile of TFQI were 3.57(95% confidence interval [CI]:1.08,11.87) and 4.90(95% CI:1.38,17.38) respectively; The odds ratio of the fourth vs. the first quartile of TSHI was 5.35(95% CI:1.48,19.37); The odds ratio of the second vs. the first quartile of TT4RI was 0.27(95%CI 0.09,0.82). In addition, no significant correlation was observed between thyroid-related measures and metabolic measures in females with PCOS. CONCLUSIONS: A reduction in the sensitivity of central thyroid hormone is closely correlated with a higher risk of PCOS. Further research is necessary to corroborate our findings and the supporting mechanisms.

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Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

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The pathogenesis of Intervertebral Disc Degeneration (IDD) is complex and multifactorial, with cellular senescence of nucleus pulposus (NP) cells and inflammation playing major roles in the progression of IDD. The stimulator of interferon genes (STING) axis is a key mediator of inflammation during infection, cellular stress, and tissue damage. Here, we present a progressive increase in STING in senescent NP cells with the degradation disorder. The STING degradation function in normal NP cells can prevent IDD. However, the dysfunction of STING degradation through autophagy causes the accumulation and high expression of STING in senescent NP cells as well as inflammation continuous activation together significantly promotes IDD. In senescent NP cells and intervertebral discs (IVDs), we found that STING autophagy degradation was significantly lower than that of normal NP cells and IVDs when STING was activated by 2'3'-cGAMP. Also, the above phenomenon was found in STINGgt/gt, cGAS-/- mice with models of age-induced, lumbar instability-induced IDD as well as found in the rat caudal IVD puncture models. Taken together, we suggested that the promotion of STING autophagy degradation in senescent NP Cells demonstrated a potential therapeutic modality for the treatment of IDD.

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