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Denitrification, anammox, and DNRA are three important nitrogen (N) reduction pathways in estuarine sediments. Although salinity is an important variables controlling microbial growth and activities, knowledge about the effects of changing salinity on those three processes in estuarine and coastal wetland sediments are not well understood. Herein, we performed a 60-d microcosms experiment with different salinities (0, 5, 15, 25 and 35 ‰) to explore the vital role of salinity in controlling N-loss and N retention in estuarine wetland sediments. The results showed that sediment organic matter, sulfide, and nitrate (NO 3 - ) were profoundly decreased with increasing salinity, while sediment ammonium (NH 4 + ) and ferrous (Fe 2+ ) varied in reverse patterns. Meanwhile, N-loss and N retention rates and associated gene abundances were differentially inhibited with increasing salinity, while the contributions of denitrification, anammox, and DNRA to total nitrate reduction were apparently unaffected. Moreover, denitrification rate was the most sensitive to salinity, and then followed by DNRA, while anammox was the weakest among these three processes. In other words, anammox bacteria showed a wide range of salinity tolerance, while both denitrification and DNRA reflected a relatively limited dynamic range of it. Our findings could provide insights into temporal interactive effects of salinity on sediment physico-chemical properties, N reduction rates and associated gene abundances. Our findings can improve understanding of the effects of saltwater incursion on the N fate and N balance in estuarine and coastal sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Sr 2 IrO 4 has attracted considerable attention due to its structural and electronic similarities to La 2 CuO 4 , the parent compound of high- T c superconducting cuprates. It was proposed as a strong spin-orbit-coupled J eff = 1/2 Mott insulator, but the Mott nature of its insulating ground state has not been conclusively established. Here, we use ultrafast laser pulses to realize an insulator-metal transition in Sr 2 IrO 4 and probe the resulting dynamics using time- and angle-resolved photoemission spectroscopy. We observe a gap closure and the formation of weakly renormalized electronic bands in the gap region. Comparing these observations to the expected temperature and doping evolution of Mott gaps and Hubbard bands provides clear evidence that the insulating state does not originate from Mott correlations. We instead propose a correlated band insulator picture, where antiferromagnetic correlations play a key role in the gap opening. More broadly, our results demonstrate that energy-momentum-resolved nonequilibrium dynamics can be used to clarify the nature of equilibrium states in correlated materials., Competing Interests: Competing interests statement:The authors declare no competing interest.

Lignin, as an abundant organic carbon, plays a vital role in the global carbon cycle. However, our understanding of the global lignin-degrading microbiome remains elusive. The greatest barrier has been absence of a comprehensive and accurate functional gene database. Here, we first developed a curated functional gene database (LCdb) for metagenomic profiling of lignin degrading microbial consortia. Via the LCdb, we draw a clear picture describing the global biogeography of communities with lignin-degrading potential. They exhibit clear niche differentiation at the levels of taxonomy and functional traits. The terrestrial microbiomes showed the highest diversity, yet the lowest correlations. In particular, there were few correlations between genes involved in aerobic and anaerobic degradation pathways, showing a clear functional redundancy property. In contrast, enhanced correlations, especially closer inter-connections between anaerobic and aerobic groups, were observed in aquatic consortia in response to the lower diversity. Specifically, dypB and dypA, are widespread on Earth, indicating their essential roles in lignin depolymerization. Estuarine and marine consortia featured the laccase and mnsod genes, respectively. Notably, the roles of archaea in lignin degradation were revealed in marine ecosystems. Environmental factors strongly influenced functional traits, but weakly shaped taxonomic groups. Null mode analysis further verified that composition of functional traits was deterministic, while taxonomic composition was highly stochastic, demonstrating that the environment selects functional genes rather than taxonomic groups. Our study not only develops a useful tool to study lignin degrading microbial communities via metagenome sequencing but also advances our understanding of ecological traits of these global microbiomes., (© 2024 John Wiley & Sons Ltd.)

Motivation: Biological background knowledge plays an important role in the manual quality assurance (QA) of biological database records. One such QA task is the detection of inconsistencies in literature-based Gene Ontology Annotation (GOA). This manual verification ensures the accuracy of the GO annotations based on a comprehensive review of the literature used as evidence, Gene Ontology (GO) terms, and annotated genes in GOA records. While automatic approaches for the detection of semantic inconsistencies in GOA have been developed, they operate within predetermined contexts, lacking the ability to leverage broader evidence, especially relevant domain-specific background knowledge. This paper investigates various types of background knowledge that could improve the detection of prevalent inconsistencies in GOA. In addition, the paper proposes several approaches to integrate background knowledge into the automatic GOA inconsistency detection process., Results: We have extended a previously developed GOA inconsistency dataset with several kinds of GOA-related background knowledge, including GeneRIF statements, biological concepts mentioned within evidence texts, GO hierarchy and existing GO annotations of the specific gene. We have proposed several effective approaches to integrate background knowledge as part of the automatic GOA inconsistency detection process. The proposed approaches can improve automatic detection of self-consistency and several of the most prevalent types of inconsistencies., This is the first study to explore the advantages of utilizing background knowledge and to propose a practical approach to incorporate knowledge in automatic GOA inconsistency detection. We establish a new benchmark for performance on this task. Our methods may be applicable to various tasks that involve incorporating biological background knowledge., Availability and Implementation: https://github.com/jiyuc/de-inconsistency., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Ovarian cancer, the most devastating tumor in women globally, significantly impacts young women, compromising their daily lives and overall well-being. Ovarian cancer represents a significant public health concern due to its extensive physical and psychological consequences., Material and Methods: Data from the Global Burden of Disease were used to assess the global, regional, and national burden of ovarian cancer in young women aged 20-39 from 1990 to 2019. This analysis focused on trends measured by the estimated annual percentage change and explored the socioeconomic impacts via the socio-demographic index (SDI)., Results: During 1990-2019, the incidence and prevalence of ovarian cancer among young women increased globally, with annual rates of 0.74% and 0.89%, respectively. The mortality rate and disability-adjusted life years also rose annually by 0.20% and 0.23%, respectively. A significant burden shift was observed toward regions with lower SDI, with high fasting plasma glucose, BMI, and asbestos exposure identified as prominent risk factors, particularly in lower SDI regions., Conclusion: Our findings underscore ovarian cancer in young women as an escalating global health challenge, with the burden increasingly shifting toward lower socioeconomic areas. This underscores the necessity for targeted prevention and control strategies for ovarian cancer, focusing on reducing the identified risk factors and ensuring equitable health resource distribution., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The prevalence of diabetes has increased rapidly, and comorbid chronic conditions are common among diabetes patients. However, little is known about the pattern of multimorbidity in diabetes patients and the effect on physical and cognitive function. This study aimed to assess the disease clusters and patterns of multimorbidity in diabetes patients using a novel latent class analysis (LCA) approach in middle-aged and older adults and explore the association between different clusters of multimorbidity in diabetes and the effect on physical and cognitive function., Methods: This national observational study included 1,985 diabetes patients from the four waves of the China Health and Retirement Longitudinal Study (CHARLS) in 2011 to 2018. Thirteen chronic diseases were used in latent class analysis to identify the patterns of multimorbidity in diabetes, which span the cardiovascular, physical, psychological, and metabolic systems. Cognitive function is assessed via a structured questionnaire in three domains: memory, executive function, and orientation. We combined activities of daily living (ADL) with instrumental activities of daily living (IADL) to measure physical function. Linear mixed models and negative binomial regression models were used to analyze the association between patterns of multimorbidity in diabetes and the effect on cognitive function and disability, respectively., Results: A sample of 1,985 diabetic patients was identified, of which 1,889 (95.2%) had multimorbidity; their average age was 60.6 years (standard deviation (SD) = 9.5), and 53.1% were women. Three clusters were identified: "cardio-metabolic" ( n  = 972, 51.5%), "mental-dyslipidemia-arthritis" ( n  = 584, 30.9%), and "multisystem morbidity" ( n  = 333, 17.6%). Compared with diabetes alone, the "multisystem morbidity" class had an increased association with global cognitive decline. All patterns of multimorbidity were associated with an increased risk of memory decline and disability; however, the "multisystem morbidity" group also had the strongest association and presented a higher ADL-IADL disability (ratio = 4.22, 95% CI = 2.52, 7.08) and decline in memory Z scores ( β  = -0.322, 95% CI = -0.550, -0.095, p  = 0.0058)., Conclusion: Significant longitudinal associations between different patterns of multimorbidity in diabetes patients and memory decline and disability were observed in this study. Future studies are needed to understand the underlying mechanisms and common risk factors for multimorbidity in diabetes patients and to propose treatments that are more effective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Qin, Li, Chen, Zhang and Ye.)

Aims: To explore the relationship between health personality and quality of life among community-dwelling older adults and to examine the mediating effect of eHealth literacy on this relationship., Methods: A total of 413 community-dwelling older adults from central China were recruited from September 2022 to January 2023. A cross-sectional investigation was conducted using the Chinese versions of the Health Personality Assessment (HPA), eHealth Literacy Scale (eHEALS), and 12-item Short Form Health Survey (SF-12). Correlations between the three variables were examined by Pearson analysis, and mediation analysis was conducted to explore the direct, indirect, and total effects of the health personality on quality of life vis-à-vis eHealth literacy., Results: Health personality factors (including health neuroticism, health openness, and health conscientiousness), eHealth literacy, and quality of life are significantly correlated (P<0.05); eHealth literacy can play a significant mediating role in the relationship between health neuroticism (β= -0.256, 95 %CI: [-0.405, -0.119]), health openness (β = 0.488, 95 % CI: [0.343,0.652]), health conscientiousness (β= 0.489, 95 % CI: [0.354, 0.634]) and quality of life., Conclusion: This study revealed that the effect of health personality factors (including health neuroticism, health openness, and health conscientiousness) on quality of life in older adults was mediated through eHealth literacy., Impact: Individual personality is essential to understanding eHealth literacy and quality of life among community-dwelling older adults. It may be helpful to identify the health personality traits of older adults first, then implement targeted interventions accordingly to enhance eHealth literacy and ultimately improve quality of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The objective of this research was to evaluate and compare the pharmacokinetic profiles and safety of lisinopril/hydrochlorothiazide (10 mg/12.5 mg) tablets in the test and reference formulations administered to participants in both fasting and postprandial states and to evaluate the bioequivalence of the 2 products in healthy Chinese volunteers. This study employed a single-center, randomized, open-label, single-dose dosing trial involving a cumulative 96 healthy adult participants (60 in the fasting group and 36 in the postprandial group). Each group comprised 2 sequence sets, and a 2-week washout period was implemented. There were no statistically significant differences in time to maximum concentration and terminal elimination half-life between the test and control groups under fasting and postprandial conditions (P > .05), and the 90% CIs for area under the plasma concentration-time curve and maximum plasma concentration were within the bioequivalence range of 80%-125%. Pharmacokinetic results indicate a large food effect for lisinopril, meaning that there is a loss of approximately 20%-25% of systemic exposure from fasting to postprandial administration for both preparations. The study demonstrated that a single oral dose of generic lisinopril/hydrochlorothiazide is bioequivalent to the reference product and well tolerated, with no significant adverse events observed, and that both products are similarly safe in a cohort of healthy Chinese male and female participants, following administration under fasting and postprandial conditions., (© 2023, The American College of Clinical Pharmacology.)

The purpose of this study was to prepare phosphorylated Athyrium multidentatum (Doll.) Ching polysaccharide (PPS) and investigate its protective effect on vascular endothelial cells (VECs) in vitro and in vivo and the underlying mechanisms. Sodium tripolyphosphate (STPP) and sodium trimetaphosphate (STMP) were used as phosphorylation reagents and PPS was characterized by Fourier transform infrared (FT-IR), 13 C nuclear magnetic resonance ( 13 C NMR) and 31 P nuclear magnetic resonance ( 31 P NMR) spectra. Chemical analysis demonstrated that PPS was composed of mannose, glucosamine, rhamnose, glucuronic acid, galacturonic acid, galactosamine, glucose, galactose, xylose, arabinose, and fucose with a molar ratio of 11.36:0.42:4.03:1.12:1.81:0.26:33.25:24.12:6.85:14.46:2.32 and a molecular weight of 28,837 Da. Results from in vitro and in vivo assays revealed that PPS protected human umbilical vein endothelial cells (HUVECs) against H 2 O 2 -induced oxidative injury and attenuated D-galactose-induced VECs damage in mice. RNA sequencing (RNA-seq) analysis identified 18 differentially expressed genes (DEGs) between D-galactose-treated and PPS-pretreated mice abdominal aorta. A deep analysis of these DEGs disclosed that PPS regulated the expression of genes involved in the functions of vascular endothelium repairment, cell growth and proliferation, cell survival and apoptosis, inflammation, angiogenesis and antioxidant, indicating that these biological processes might play crucial roles in the protective actions of PPS on VECs., (© 2023 John Wiley & Sons Ltd.)

Lignocellulose, as the most abundant natural organic carbon on earth, plays a key role in regulating the global carbon cycle, but there have been only few studies in marine ecosystems. Little information is available about the extant lignin-degrading bacteria in coastal wetlands, limiting our understanding of their ecological roles and traits in lignocellulose degradation. We utilized in situ lignocellulose enrichment experiments coupled with 16S rRNA amplicon and shotgun metagenomics sequencing to identify and characterize bacterial consortia attributed to different lignin/lignocellulosic substrates in the southern-east intertidal zone of East China Sea. We found the consortia enriched on woody lignocellulose showed higher diversity than those on herbaceous substrate. This also revealed substrate-dependent taxonomic groups. A time-dissimilarity pattern with increased alpha diversity over time was observed. Additionally, this study identified a comprehensive set of genes associated with lignin degradation potential, containing 23 gene families involved in lignin depolymerization, and 371 gene families involved in aerobic/anaerobic lignin-derived aromatic compound pathways, challenging the traditional view of lignin recalcitrance within marine ecosystems. In contrast to similar cellulase genes among the lignocellulose substrates, significantly different ligninolytic gene groups were observed between consortia under woody and herbaceous substrates. Importantly, we not only observed synergistic degradation of lignin and hemi-/cellulose, but also pinpointed the potential biological actors at the levels of taxa and functional genes, which indicated that the alternation of aerobic and anaerobic catabolism could facilitate lignocellulose degradation. Our study advances the understanding of coastal bacterial community assembly and metabolic potential for lignocellulose substrates. IMPORTANCE It is essential for the global carbon cycle that microorganisms drive lignocellulose transformation, due to its high abundance. Previous studies were primarily constrained to terrestrial ecosystems, with limited information about the role of microbes in marine ecosystems. Through in situ lignocellulose enrichment experiment coupled with high-throughput sequencing, this study demonstrated different impacts that substrates and exposure times had on long-term bacterial community assembly and pinpointed comprehensive, yet versatile, potential decomposers at the levels of taxa and functional genes in response to different lignocellulose substrates. Moreover, the links between ligninolytic functional traits and taxonomic groups of substrate-specific populations were revealed. It showed that the synergistic effect of lignin and hemi-/cellulose degradation could enhance lignocellulose degradation under alternation of aerobic and anaerobic conditions. This study provides valuable taxonomic and genomic insights into coastal bacterial consortia for lignocellulose degradation., Competing Interests: The authors declare no conflict of interest.

Various culture conditions by small molecules have been explored to extend pluripotency of stem cells, but their impacts on cell fate in vivo remain elusive. We systematically compared the effects of various culture conditions on the pluripotency and cell fate in vivo of mouse embryonic stem cells (ESCs) by tetraploid embryo complementation assay. Conventional ESC cultures in serum/LIF-based condition produced complete ESC mice and also the survival to adulthood at the highest rates of all other chemical-based cultures. Moreover, long-term examination of the survived ESC mice demonstrated that conventional ESC cultures did not lead to visible abnormality for up to 1.5-2 years, whereas the prolonged chemical-based cultures developed retroperitoneal atypical teratomas or leiomyomas. The chemical-based cultures exhibited transcriptomes and epigenomes that typically differed from those of conventional ESC cultures. Our results warrant further refinement of culture conditions in promoting the pluripotency and safety of ESCs in future applications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The Health Personality Assessment (HPA) is a reliable and brief instrument to evaluating personality in the health domain, but it has not been used in China., Objectives: To cross-culturally adapt and evaluate the psychometric property of HPA among Chinese older adults., Methods: The Chinese version of HPA was generated following Beaton's guidelines. The psychometric evaluation of the HPA was conducted on 482 community-dwelling older adults., Results: The Chinese version of HPA showed good internal consistency, item-total correlations, criterion validity, and test-retest reliability within a 2-week interval. Results of confirmatory factor analysis indicated a satisfactory model fit, convergent validity and discriminant validity were also in the acceptable range., Conclusions: HPA showed good reliability and validity among the Chinese population. The generalization of the HPA may provide a new tool for health practitioners from the personality perspective., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Potassium (K + ) is an endogenous substance that is an essential dietary component. However, the interaction between dietary arrangements and specific effects of dietary K + intake in bioequivalence studies remains unclear. To investigate the influence of dietary arrangement on the bioequivalence of potassium chloride (KCl) sustained-release tablets in healthy Chinese volunteers, the pharmacokinetics of KCl were compared in two open-label, single-center, randomized, two-period crossover studies with different dietary conditions. All volunteers received an oral dose of 6 g of KCl sustained-release tablets under fasting conditions, with different dietary arrangements. Urine samples were collected on baseline days and 48 hours after tablet consumption. Inductively coupled plasma-optical emission spectrometry was used to measure the concentration of K + in the urine samples. Pharmacokinetic parameters were analyzed using Phoenix WinNonlin software in a noncompartmental model. In either clinical trial, no significant differences were observed in the maximal rate of urinary excretion and cumulative urinary excretion from 0 to 24 hours of K + between the reference and test drugs. The bioequivalence studies of both KCl sustained-release tablet formulations were successfully conducted under different dietary conditions., (© 2022, The American College of Clinical Pharmacology.)

Functional telomeres protect chromosome ends and play important roles in stem cell maintenance and differentiation. Short telomeres negatively impact germ cell development and can contribute to age-associated infertility. Moreover, telomere syndrome resulting from mutations of telomerase or telomere-associated genes exhibits short telomeres and reduced fertility. It remains elusive whether and how telomere lengths affect germ cell specification. We report that functional telomere is required for the coordinated germ cell and somatic cell fate decisions. Using telomerase gene Terc deficient mice as a model, we show that short telomeres restrain germ cell specification of epiblast cells but promote differentiation towards somatic lineage. Short telomeres increase chromatin accessibility to elevate TGFβ and MAPK/ERK signaling for somatic cell differentiation. Notably, elevated Fst expression in TGFβ pathway represses the BMP4-pSmad signaling pathway, thus reducing germ cell formation. Re-elongation of telomeres by targeted knock-in of Terc restores normal chromatin accessibility to suppress TGFβ and MAPK signaling, thereby facilitating germ cell formation. Taken together, our data reveal that functional telomeres are required for germ cell specification by repressing TGFβ and MAPK signaling., (© 2022. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Leaf veins constitute the transport network for water and photosynthetic assimilates in vascular plants. The class III homeodomain-leucine zipper ( HD-Zip III ) gene family is central to the regulation of vascular development. In this research, we performed an overall analysis of the HD-Zip III genes in soybean ( Glycine max L. Merr.). Our analysis included the phylogeny, conservation domains and cis -elements in the promoters of these genes. We used the quantitative reverse transcription-polymerase chain reaction to characterize the expression patterns of HD-Zip III genes in leaf vein development and analyze the effects of exogenous hormone treatments. In this study, twelve HD-Zip III genes were identified from the soybean genome and named. All soybean HD-Zip III proteins contained four highly conserved domains. GmHB15-L-1 transcripts showed steadily increasing accumulation during all stages of leaf vein development and were highly expressed in cambium cells. GmREV-L-1 and GmHB14-L-2 had nearly identical expression patterns in soybean leaf vein tissues. GmREV-L-1 and GmHB14-L-2 transcripts remained at stable high levels at all xylem developmental stages. GmREV-L-1 and GmHB14-L-2 were expressed at high levels in the vascular cambium and xylem cells. Overall, GmHB15-L-1 may be an essential regulator that is responsible for the formation or maintenance of soybean vein cambial cells. GmREV-L-1 and GmHB14-L-2 were correlated with xylem differentiation in soybean leaf veins. This study will pave the way for identifying the molecular mechanism of leaf vein development.

Motivation: Literature-based gene ontology annotations (GOA) are biological database records that use controlled vocabulary to uniformly represent gene function information that is described in the primary literature. Assurance of the quality of GOA is crucial for supporting biological research. However, a range of different kinds of inconsistencies in between literature as evidence and annotated GO terms can be identified; these have not been systematically studied at record level. The existing manual-curation approach to GOA consistency assurance is inefficient and is unable to keep pace with the rate of updates to gene function knowledge. Automatic tools are therefore needed to assist with GOA consistency assurance. This article presents an exploration of different GOA inconsistencies and an early feasibility study of automatic inconsistency detection., Results: We have created a reliable synthetic dataset to simulate four realistic types of GOA inconsistency in biological databases. Three automatic approaches are proposed. They provide reasonable performance on the task of distinguishing the four types of inconsistency and are directly applicable to detect inconsistencies in real-world GOA database records. Major challenges resulting from such inconsistencies in the context of several specific application settings are reported. This is the first study to introduce automatic approaches that are designed to address the challenges in current GOA quality assurance workflows. The data underlying this article are available in Github at https://github.com/jiyuc/AutoGOAConsistency., (© The Author(s) 2022. Published by Oxford University Press.)

The inflammatory response is the key pathophysiological character of acute lung injury (ALI). Berberine (BBR), a natural quaternary ammonium alkaloid, plays a functional role in anti-inflammation both in vitro and in vivo . However, the underlying mechanism between BBR and ALI has not been expounded. Here, we found that BBR improved the permeability of pulmonary and repressed the inflammatory factors in the lipopolysaccharides (LPSs)-induced ALI model. We demonstrated that BBR could suppress the expression of phosphorylated nuclear factor-kappa B (NF-κB) and further restrain the downstream gene nucleotide-binding domain and leucine-rich repeat protein-3 (Nlrp3). Moreover, we also revealed that BBR could directly interact with Nlrp3 protein. After knocked down of Nlrp3 by using siRNA, the protective role of BBR was abrogated in vitro . The expression of IL-1β and IL-18 was downregulated by BBR via the two signaling pathways. Notably, in Nlrp3 deficient mice, the protective effect of BBR was abolished. These findings demonstrate that BBR has a depressant effect on inflammatory response caused by LPS via regulating NF-κB/Nlrp3 signaling pathway, providing a potential therapeutic strategy in ALI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Huang, Bian and He.)

Aged bone marrow mesenchymal stem cells (BMSCs) exhibit aberrant self-renewal and lineage specification, which contribute to imbalanced bone-fat and progressive bone loss. In addition to known master regulators of lineage commitment, it is crucial to identify pivotal switches governing the specific differentiation fate of aged BMSCs. Here, we profiled differences in epigenetic regulation between adipogenesis and osteogenesis and identified super-enhancer associated lncRNA nuclear-enriched abundant transcript 1 (NEAT1) as a key bone-fat switch in aged BMSCs. We validated that NEAT1 with high enhancer activity was transcriptionally activated by ATF2 and directed aged BMSCs to a greater propensity to differentiate toward adipocytes than osteoblasts by mediating mitochondrial function. Furthermore, we confirmed NEAT1 as a protein-binding scaffold in which phosphorylation modification of SOX2 Ser249/250 by CDK2 impaired SOX2/OCT4 complex stability and dysregulated downstream transcription networks of pluripotency maintenance. In addition, by sponging miR-27b-3p, NEAT1 upregulated BNIP3L, BMP2K, and PPARG expression to shape mitochondrial function and osteogenic/adipogenic differentiation commitment, respectively. In extracellular communication, NEAT1 promoted CSF1 secretion from aged BMSCs and then strengthened osteoclastic differentiation by extracellular vesicle delivery. Notably, Neat1 small interfering RNA delivery induced increased bone mass in aged mice and decreased fat accumulation in the bone marrow. These findings suggest that NEAT1 regulates the lineage fates of BMSCs by orchestrating mitochondrial function and pluripotency maintenance, and might be a potential therapeutic target for skeletal aging., (© 2021. The Author(s).)

Background: Depletion of oocytes leads to ovarian aging-associated infertility, endocrine disruption and related diseases. Excitingly, unlimited oocytes can be generated by differentiation of primordial germ cell like cells (PGCLCs) from pluripotent stem cells. Nevertheless, development of oocytes and follicles from PGCLCs relies on developmentally matched gonadal somatic cells, only available from E12.5 embryos in mice. It is therefore imperative to achieve an in vitro source of E12.5 gonadal somatic cells., Methods: We explored to identify small molecules, which can induce female embryonic stem cells (ESCs) into gonadal somatic cell like cells., Results: Using RNA-sequencing, we identified signaling pathways highly upregulated in E12.5&#95;gonadal somatic cells (E12.5&#95;GSCs). Through searching for the activators of these pathways, we identified small-molecule compounds Vitamin C (Vc) and AM580 in combination (V580) for inducing differentiation of female embryonic stem cells (ESCs) into E12.5&#95;GSC-like cells (E12.5&#95;GSCLCs). After V580 treatment for 6 days and sorted by a surface marker CD63, the cell population yielded a transcriptome profile similar to that of E12.5&#95;GSCs, which promoted meiosis progression and folliculogenesis of primordial germ cells. This approach will contribute to the study of germ cell and follicle development and oocyte production and have implications in potentially treating female infertility., Conclusion: ESCs can be induced into embryonic gonadal somatic cell like cells by small molecules., (© 2021. The Author(s).)

Background: Literature-based gene ontology (GO) annotation is a process where expert curators use uniform expressions to describe gene functions reported in research papers, creating computable representations of information about biological systems. Manual assurance of consistency between GO annotations and the associated evidence texts identified by expert curators is reliable but time-consuming, and is infeasible in the context of rapidly growing biological literature. A key challenge is maintaining consistency of existing GO annotations as new studies are published and the GO vocabulary is updated., Results: In this work, we introduce a formalisation of biological database annotation inconsistencies, identifying four distinct types of inconsistency. We propose a novel and efficient method using state-of-the-art text mining models to automatically distinguish between consistent GO annotation and the different types of inconsistent GO annotation. We evaluate this method using a synthetic dataset generated by directed manipulation of instances in an existing corpus, BC4GO. We provide detailed error analysis for demonstrating that the method achieves high precision on more confident predictions., Conclusions: Two models built using our method for distinct annotation consistency identification tasks achieved high precision and were robust to updates in the GO vocabulary. Our approach demonstrates clear value for human-in-the-loop curation scenarios., (© 2021. The Author(s).)

Atherosclerosis-associated cardiovascular disease is one of the main causes of death and disability among patients with diabetes mellitus. However, little is known about the impact of S-nitrosylation in diabetes-accelerated atherosclerosis. Here, we show increased levels of S-nitrosylation of guanine nucleotide-binding protein G(i) subunit alpha-2 (SNO-GNAI2) at Cysteine 66 in coronary artery samples from diabetic patients with atherosclerosis, consistently with results from mice. Mechanistically, SNO-GNAI2 acted by coupling with CXCR5 to dephosphorylate the Hippo pathway kinase LATS1, thereby leading to nuclear translocation of YAP and promoting an inflammatory response in endothelial cells. Furthermore, Cys-mutant GNAI2 refractory to S-nitrosylation abrogated GNAI2-CXCR5 coupling, alleviated atherosclerosis in diabetic mice, restored Hippo activity, and reduced endothelial inflammation. In addition, we showed that melatonin treatment restored endothelial function and protected against diabetes-accelerated atherosclerosis by preventing GNAI2 S-nitrosylation. In conclusion, SNO-GNAI2 drives diabetes-accelerated atherosclerosis by coupling with CXCR5 and activating YAP-dependent endothelial inflammation, and reducing SNO-GNAI2 is an efficient strategy for alleviating diabetes-accelerated atherosclerosis., (© 2021. The Author(s).)

Insufficient pancreatic β-cell or insulin-producing β-cell are implicated in all types of diabetes mellitus. Our previous studies showed bee pollen polysaccharide RBPP-P improves insulin resistance in type 2 diabetic mice by inhibiting liver fat deposition. However, its potential of regulating β-cell function and integrity is not fully known. Herein, we observed that β-cell proliferation ( n = 10), insulin synthesis ( n = 5, p = 0.01684) and insulin incretion ( n = 5, p = 0.02115) were intensely activated in MIN6 cells when treatment with RBPP-P. In alloxan-induced diabetic mice, oral administration of RBPP-P ( n = 10) effectively decreased the blood glucose ( p = 0.0326), drink intake ( p < 0.001) and urine ( p < 0.001). It directly stimulated phosphorylation of p38 ( p = 0.00439), ERK ( p = 0.02951) and AKT ( p = 0.0072) to maintain the islet function and mass. Thus, our data suggest that RBPP-P is a natural compound to regulate β-cell proliferation and function, indicating it might have therapeutic potential against type 1 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Qu, Chen, Chen, Sun, Zhou and Fan.)

It has been well established that leukemia inhibitory factor (LIF) is essential for maintaining naïve pluripotency of embryonic stem cells (ESCs). Oncostatin M (OSM) is a member of the IL-6 family of cytokines which share gp130 as a receptor subunit, and the OSM-gp130 complex can recruit either LIF receptor β or OSM receptor β. Here we show that OSM can completely replace LIF to maintain naïve pluripotency of ESCs. Mouse ESCs (mESCs) cultured in the presence of LIF or OSM not only express pluripotency genes at similar levels but also exhibit the same developmental pluripotency as evidenced by the generation of germline competent chimeras, supporting previous findings. Moreover, we demonstrate by tetraploid embryo complementation assay, the most stringent functional test of authentic pluripotency that mESCs cultured in OSM produce viable all-ESC pups. Furthermore, telomere length and telomerase activity, which are also crucial for unlimited self-renewal and genomic stability of mESCs, do not differ in mESCs cultured under OSM or LIF. The transcriptome of mESCs cultured in OSM overall is very similar to that of LIF, and OSM activates Stat3 signaling pathway, like LIF. Additionally, OSM upregulates pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and steroid and retinol metabolic pathways. Although the significance of these pathways remains to be determined, our data shows that OSM can maintain naïve pluripotent stem cells in the absence of LIF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ye, Tian, Liu, Feng, Jin, Wang, Chen and Liu.)

Objective: This study aimed to focus on the atlantoaxial pedicle screw placement and evaluate the effects of anatomical data and degree of surgical exposure of the atlantoaxial pedicle screw trajectory determined using spiral CT on the reference sites for pedicle screw insertion and various parameters in clinical application., Method: The data of CT scan of cervical spine from individuals treated in our hospital were selected. Various anatomical parameters of the atlantoaxial pedicle screw trajectory were measured through multiplanar reconstruction (MPR) technology. Anatomical data and degree of surgical exposure of the atlantoaxial pedicle screw trajectory were obtained through spiral CT. Vernier calipers with least count of 0.01 mm was selected and the least count of the protractor was 0.2°. Prism 8.0 was adopted for graphical data analysis. The anatomical data of atlas of the local population were established. The measurement technique for pedicle screw trajectory and the method for pedicle screw insertion were mastered., Results: The results indicated that the intraoperative blood loss was between 30-280 ml with no case of excessive blood loss. Follow-up studies 10-18 months after the operations indicated stability of upper cervical spine without adverse conditions. The width of the pedicle screw was 13-24 mm, and the maximal inclination angle of the horizontal for the insertion was 17-21°., Conclusion: The atlantoaxial pedicle screw placement was an effective surgical treatment for stabilizing the upper cervical spine. The measurement data of the atlantoaxial pedicle screw path was obtained through spiral CT and the surgical placement of pedicle screw was guided through individual data. Postoperative CT scan was adopted to evaluate the accuracy of pedicle screw placement, record the occurrence of secondary injuries, improve the stability of clinical applications, and reduce the risks for patients., Competing Interests: None., (AJTR Copyright © 2021.)

In this study, we investigated the protective effects of gastrodin (Gas) against homocysteine-induced human umbilical vein endothelial cell (HUVEC) injury and the role of the phosphoinositide 3-kinase (PI3K)/threonine kinase 1 (Akt)/endothelial nitric oxide synthase (eNOS) and NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathways. We stimulated cells with homocysteine (1 mmol/L, 24 hours) and tested the effects of gastrodin (200-800 μg/mL) on cell viability and the production of malondialdehyde (MDA), lactate dehydrogenase (LDH) and reactive oxygen species (ROS). Then, Nrf2 distribution in the cytoplasm and nucleus as well as the expression of enzymes downstream of Nrf2 was determined. Furthermore, we analysed the expression of bax, bcl-2 and cleaved caspase3, and assessed the involvement of the PI3K/Akt/eNOS pathway by Western blots. Finally, we tested the vasoactive effect of gastrodin in thoracic aortic rings. The results showed that gastrodin decreased MDA, LDH and ROS production and increased cell viability, NO production and relaxation of thoracic aortic rings. Moreover, the protective effects of Gas on NO production and relaxation of thoracic aortic rings were blocked by L-NAME but enhanced by Cav-1 knockdown, and MK-2206 treatment abolished the effect of Gas on the ROS. In addition, treatment with gastrodin increased Nrf2 nuclear translocation, thus enhancing the expression of downstream enzymes. Finally, gastrodin increased the expression of PI3K, p-Akt, and eNOS and decreased Cav-1 protein expression. In conclusion, our study suggested that gastrodin may protect HUVECs from homocysteine-induced injury, and the PI3K/Akt/eNOS and Nrf2/ARE pathways may be responsible for the efficacy of gastrodin., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: Transoral endoscopic thyroidectomy via vestibular approach (TOETVA), with its excellent cosmetic effect, has become increasingly popular worldwide. Nonetheless, anatomic obstacles have limited its development to a certain extent. Here, we present our preliminary outcomes of transoral endoscopic thyroidectomy via submental and vestibular approach (TOETSMVA), which can overcome those limitations. Methods: From November 2019 to March 2020, we performed TOETSMVA in 21 consecutive patients with thyroid carcinoma at Zhongshan Hospital, Xiamen University. A 1.5-cm lateral incision was made at two fingers below the mandible; two 5-mm incisions were made in the vestibule near the first molars; TOETSMVA was completed through these incisions. The demographic data and surgical outcomes of the patients were retrospectively reviewed. Results: Twenty-one patients with a mean age of 37.5 ± 10.4 years were incorporated into this study. Fourteen patients had papillary thyroid micro-carcinomas, two had papillary thyroid carcinomas, and five had benign nodules. Eight patients had lymph node metastases. All surgeries were performed successfully without conversion to open thyroidectomy. The mean operation time was 138.8 ± 33.2 min; the average hospital stay was 3.3 ± 0.8 days. No patients developed cutaneous paralysis in the midline chin region. Transient recurrent laryngeal nerve paralysis was observed in one patient. There was no evidence of postoperative bleeding, infection, tetany, or other complications. Conclusion: TOETSMVA was shown to be a safe and advisable alternative for selected patients. This approach can overcome the limitations of TOETVA without sacrificing cosmetic results., (Copyright © 2020 Fu, Wu, Fu, Lin, Song, Chen, Yan, Kuang, Lin, Luo, Lin, Hong and Wu.)

Quantitative real-time PCR (qPCR) has become a widely used approach to analyze the expression level of selected genes. However, owing to variations in cell types and drug treatments, a suitable reference gene should be selected according to special experimental design. In this study, we investigated the expression level of ten candidate reference genes in hepatoma carcinoma cell (HepG2) and human hepatocyte cell line (L02) treated with ethanol (EtOH), hydrogen peroxide (H 2 O 2 ), acetaminophen (APAP), and carbon tetrachloride (CCl 4 ), respectively. To analyze raw cycle threshold values (Cp values) from qPCR run, three reference gene validation programs, including Bestkeeper, geNorm, and NormFinder, were used to evaluate the stability of ten candidate reference genes. The results showed that TATA-box binding protein ( TBP ) and tubulin beta 2a ( TUBB2a ) presented the highest stability for normalization under different treatments and were regarded as the most suitable reference genes of HepG2 and L02. In addition, this study not only identified the most stable reference genes of each treatment, but also suggested that β -actin ( ACTB ), glyceraldehade-3-phosphate dehydrogenase ( GAPDH ), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta ( YWHAZ ), and beta-2 microglobulin ( B2M ) were the least stable reference genes in HepG2 and L02. This work was the first report to systematically explore the stability of reference genes in injured models of HepG2 and L02., Competing Interests: The authors did not report any conflict of interest., (Copyright © 2020 Jiyu Chen et al.)

Real time quantitative reverse transcription PCR (RT-qPCR) has been attracting more attention for its high sensitivity in gene expression analysis. Given the widely use of RT-qPCR in normalization, it is playing a pivotal role for seeking suitable reference genes in different species. In current work, 12 candidate reference genes including Actin 2 (ACT2), Cyclophilin 2 (CYP2), Glyceraldehyde-3-phosphate dehydrogenase C2 (GAPC2), Elongation factor 1-α (EF1-α), Nuclear cap binding protein 20 (NCBP20), Serine/threonine-protein phosphatase PP2A (PP2A), Polypyrimidine tract-binding protein 1 (PTBP1), SAND family protein (SNAD), TIP41-like protein (TIP41), Tubulin beta-6 (TUB6), Ubiquitin-conjugating enzyme 9 (UBC9) and Glyceraldehyde-3-phosphatedehydrogenase (GAPDH) were screened from the transcriptome datasets of M. charantia. Afterwards, GeNorm, NormFinder and BestKeeper algorithms were applied to assess the expression stability of these 12 genes under different abiotic stresses including drought, cold, high-salt, hormone, UV, oxidative and metal stress. The results indicated that 12 selected genes exhibited various stability across the samples under different external stress conditions, but TIP41, PTBP1 and PP2A presented high stability among all the reference genes. To validate the suitability of the identified reference genes, the results of hormone subset were compared with RNA sequencing (RNA-seq) data, and the relative abundance of Ascorbate peroxidase 1（APX1）was used to confirm the reliability of the results. This work assesses the stability of reference genes in M. charantia under different abiotic stress conditions, which will be beneficent for accurate normalization of target genes in M. charantia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

RAW264.7 is a macrophage strain derived from mice tumour and shows a significant ability in antigen uptake. Real-time quantitative PCR (RT-qPCR) is one of the most commonly used methods in gene studies and requires suitable reference genes to normalize and quantitate the expression of gene of interest with sensitivity and specificity. However, suitable reference genes in RAW264.7 cells have not yet been identified for accurate gene expression quantification. In the current study, we evaluated expression levels of ten candidate reference genes in RAW264.7 cells under different conditions. RT-qPCR results indicated significant differences in the expression levels among the ten reference genes. Statistical analyses were carried out using geNorm, NormFinder, and BestKeeper software to further investigate the stability of the reference genes. Integrating the results from the three analytical methods, cytochrome c-1 and hydroxymethylbilane synthase were found to be the most stable and therefore more suitable reference genes, while ribosomal protein L4 and cyclophilin A were the least stable. This study emphasises the importance of identifying and selecting the most stable reference genes for normalization and provides a basis for future gene expression studies using RAW264.7 cells.

Despite comprising a small portion of the earth's surface, lakes are vitally important for global ecosystem cycling. However, lake systems worldwide are extremely fragile, and many are shrinking due to changing climate and anthropogenic activities. Here, we show that Poyang Lake, the largest freshwater lake in China, has experienced a dramatic and prolonged recession, which began in late September of 2003. We further demonstrate that abnormally low levels appear during October, 28 days ahead of the normal initiation of the dry season, which greatly imperiled the lake's wetland areas and function as an ecosystem for wintering waterbirds. An increase in the river-lake water level gradient induced by the Three Gorges Dam (TGD) altered the lake balance by inducing greater discharge into the Changjiang River, which is probably responsible for the current lake shrinkage. Occasional episodes of arid climate, as well as local sand mining, will aggravate the lake recession crisis. Although impacts of TGD on the Poyang Lake recession can be overruled by episodic extreme droughts, we argue that the average contributions of precipitation variation, human activities in the Poyang Lake catchment and TGD regulation to the Poyang Lake recession can be quantified as 39.1%, 4.6% and 56.3%, respectively.

While most large river-deltas in the world are facing the risk of subsidence and erosion in the Anthropocene, it is suspected that the Changjiang submerged delta (CSD) could be subjected to the impacts of the world's largest dam, the Three Gorges Dam (TGD). Here we firstly indicate that the CSD went through high accumulation (1958-1978); slight accumulation (1978-1997), slight erosion (1997-2002); and high accumulation (2002-2009), despite the 70% reduction of the sediment load from upstream since the operation of the TGD in 2003. Meanwhile, at the depocenter of the submerged delta, the accumulation maintained a high rate of 10 cm/yr during 1958-2009. This suggests on a longer term, the distal sediment source from the upstream had little effect on the CSD. Within this time frame the changes in the partition of sediment load among the branching channels of the Changjiang Estuary could likely control the shifting of the depocenter of the CSD on a decadal time scale. Episodic extreme floods and storm surges also increased the magnitude of deposition and erosion of the CSD on short-term scales. A re-evaluation of the impacts of TGD on the CSD is urgently needed.

Studies on lycopene synthesis in Escherichia coli were not only able to gain the strains with high yield and less by-products, but also able to test functions of genes or gene clusters. In this article, the cDNA sequences of tomato LeGGPS2 and LePSY1 as well as the coding sequence of crtI from Erwinia uredovora, each of which was added a ribosome biding site, were controlled by T7 promoter and terminator alone or combined, and expressed in E. coli BL21 (DE3) to induce lycopene synthesis. The results show that only T7::crtI-LeGGPS2-LePSY1 expressed tri-cistronically could produce lycopene, and 2.124 mg/g dry cell weight oflycopene was obtained when fermented for 5 h at 30 degrees C after mixing 80 micromol/L IPTG at the later logarithmic phase while the seed broth of 1:50 (V/V) was inoculated into LB medium (pH 6.8) containing 3% sucrose and cultured for 8 h at 37 degrees C. The results confirmed the function of the prokaryonized LeGGPS2 and LePSY1 and their synergy with crtI, and also laid a foundation to establish an independent lycopene synthetic pathway in the tomato plastid.