Transcriptomic Profiles of Long Noncoding RNAs and Their Target Protein-Coding Genes Reveals Speciation Adaptation on the Qinghai-Xizang (Tibet) Plateau in Orinus.

Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nt, which lack the ability to encode proteins and are involved in multifarious growth, development, and regulatory processes in plants and mammals. However, the environmental-regulated expression profiles of lncRNAs in Orinus that may associated with their adaptation on the Qinghai-Xizang (Tibet) Plateau (QTP) have never been characterized. Here, we utilized transcriptomic sequencing data of two Orinus species (O. thoroldii and O. kokonoricus) to identify 1624 lncRNAs, including 1119 intergenic lncRNAs, 200 antisense lncRNAs, five intronic lncRNAs, and 300 sense lncRNAs. In addition, the evolutionary relationships of Orinus lncRNAs showed limited sequence conservation among 39 species, which implied that Orinus-specific lncRNAs contribute to speciation adaptation evolution. Furthermore, considering the cis-regulation mechanism, from 286 differentially expressed lncRNAs (DElncRNAs) and their nearby protein coding genes (PCGs) between O. thoroldii and O. kokonoricus, 128 lncRNA-PCG pairs were obtained in O. thoroldii, whereas 92 lncRNA-PCG pairs were obtained in O. kokonoricus. In addition, a total of 19 lncRNA-PCG pairs in O. thoroldii and 14 lncRNA-PCG pairs in O. kokonoricus were found to participate in different biological processes, indicating that the different expression profiles of DElncRNAs between O. thoroldii and O. kokonoricus were associated with their adaptation at different elevations on the QTP. We also found several pairs of DElncRNA nearby transcription factors (TFs), indicating that these DElncRNAs regulate the expression of TFs to aid O. thoroldii in adapting to the environment. Therefore, this work systematically identified a series of lncRNAs in Orinus, laying the groundwork for further exploration into the biological function of Orinus in environmental adaptation.

The complete chloroplast genome of Oxytropis ochrocephala Bunge 1874 (Fabaceae) and its phylogenetic analysis.

This study presents the first-ever complete chloroplast (cp) genome sequence of Oxytropis ochrocephala Bunge 1874, a member of the Fabaceae family. The cp genome spans 126,996 base pairs and includes 109 genes, comprising 76 protein-coding genes, 29 tRNA genes, and four rRNA genes. Notably, the genome lacks an inverted repeat (IR) region. Additionally, we constructed phylogenetic trees for 34 species within Trib. Galegeae, employing both maximum likelihood (ML) and Bayesian inference (BI) methods. These analyses robustly support the monophyly of the Oxytropis species, evidenced by high bootstrap values (BP = 100) and posterior probabilities (PP = 1). Within this clade, O. ochrocephala exhibits a sister relationship with other Oxytropis species. Our findings provide valuable insights into the genetic makeup and evolutionary relationships of O. ochrocephala within the Galegeae tribe.

Exploring the Application of Graphene Oxide-Based Nanomaterials in the Repair of Osteoporotic Fractures.

Osteoporotic fractures are induced by osteoporosis, which may lead to the degradation of bone tissues and microstructures and impair their healing ability. Conventional internal fixation therapies are ineffective in the treatment of osteoporotic fractures. Hence, developing tissue engineering materials is crucial for repairing osteoporotic fractures. It has been demonstrated that nanomaterials, particularly graphene oxide (GO), possess unique advantages in tissue engineering due to their excellent biocompatibility, mechanical properties, and osteoinductive abilities. Based on that, GO-nanocomposites have garnered significant attention and hold promising prospects for bone repair applications. This paper provides a comprehensive insight into the properties of GO, preparation methods for nanocomposites, advantages of these materials, and relevant mechanisms for osteoporotic fracture applications.

Interaction between visual impairment and subjective cognitive complaints on physical activity impairment in U.S. older adults: NHANES 2005-2008.

BACKGROUND/AIM: To investigate the independent relationships of visual impairment (VI) and Subjective cognitive complaints (SCC) with physical function impairment (PFI) and the interaction effect between VI and SCC on PFI in American older adults. METHODS: The data of this cross-sectional study was obtained from the 2005-2008 National Health and Examination Survey (NHANES) conducted in the United States. The VI criterion included both subjective self-reported eyesight conditions and objective visual acuity test results. The self-reported questionnaires were utilized to determine PFI and SCC. According to the survey design of NHANS, original data were weighted to produce nationally representative estimates. Both the unweighted original data and weighted estimates underwent analysis. Crude and adjusted logistic models were employed to assess the pairwise associations among VI, SCC, and PFI. To assess the interactive effect, measures such as the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated. RESULTS: A total of 2,710 subjects (weighted n = 38,966,687) aged 60 years or older were included. Compared with subjects without subjective visual impairment (SVI), those with SVI had a significant positive association with PFI [weighted OR (95%CI): 3.11 (2.25, 4.31)]. After multi-variable adjusting, the relationship remained significant [weighted OR (95%CI): 1.90 (1.32, 2.72)]. Similarly, those with objective visual impairment (OVI) were positively associated with the risk of PFI in the crude model [weighted OR (95%CI): 2.35 (1.53, 3.61)] and adjusted model [weighted OR (95%CI): 1.84 (1.07, 3.17)]. Moreover, we found the association of SCC with an increased risk of FPI [crude weighted OR (95%CI): 5.02 (3.40, 7.40); adjusted weighted OR (95%CI): 3.29 (2.01, 5.38)]. Ultimately, the additive interaction showed there was a significant positive interaction term between SVI and SCC on PFI, while OVI and SCC did not. CONCLUSION: Both VI and SCC were significantly associated with PFI in elder adults. Besides, there was a significant synergistic interaction between SVI and SCC on PFI, which indicated the improvement of SVI and SCC may be beneficial for the prevention of PFI. For the elderly, especially those with multiple disabilities, comprehensive and targeted approaches are imperative to foster their overall well-being and health.

Nontargeted metabolomic insights into the behavioral effects of 5-MeO-MiPT in zebrafish (Danio rerio).

5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) is a novel psychoactive substance exhibiting a tryptamine structure. Despite its increasing prevalence, the environmental impact of 5-MeO-MiPT remains unexplored. Our prior investigation revealed that 5-MeO-MiPT induced inhibited spontaneous movement and prompted anxiety-like behavior in adult zebrafish-a validated toxicological model. To elucidate this phenomenon and establish a correlation between metabolomics and behavioral changes induced by 5-MeO-MiPT, zebrafish were administered varying drug concentrations. Zebrafishes were subjected to injections of different 5-MeO-MiPT concentrations. Subsequent metabolomic analysis of endogenous metabolites affected by the drug unveiled substantial variations in metabolic levels between the control group and the drug-injected cohorts. A total of 22 distinct metabolites emerged as potential biomarkers. Further scrutiny identified seven pathways significantly influenced by 5-MeO-MiPT. A focused exploration into amino acid metabolism, lipid metabolism, and energy metabolism unveiled that the metabolic repercussions of 5-MeO-MiPT on zebrafish resulted in observable brain damage. Notably, the study identified a consequential disruption in the liver-brain pathway. The comprehensive metabolomic approach employed herein effectively discerned the impact of 5-MeO-MiPT on zebrafish metabolism. This approach also shed light on the mechanism underpinning the anxiety-like behavior observed in zebrafish post-drug injection. Specifically, our findings indicate that 5-MeO-MiPT induces brain damage, particularly within the liver-brain pathway.

Comparative analysis and characterization of the chloroplast genome of Krascheninnikovia ceratoides (Amarathaceae): a xerophytic semi-shrub exhibiting drought resistance and high-quality traits.

BACKGROUND: Krascheninnikovia ceratoides, a perennial halophytic semi-shrub belonging to the genus Krascheninnikovia (Amarathaceae), possesses noteworthy ecological, nutritional, and economic relevance. This species is primarily distributed across arid, semi-arid, and saline-alkaline regions of the Eurasian continent, encompassing Inner Mongolia, Xinjiang, Qinghai, Gansu, Ningxia, and Tibet. RESULTS: We reported the comprehensive chloroplast (cp) genome of K. ceratoides, characterized by a circular conformation spanning 151,968 bp with a GC content of 36.60%. The cp genome encompassed a large single copy (LSC, 84,029 bp), a small single copy (SSC, 19,043 bp), and a pair of inverted repeats (IRs) regions (24,448 bp each). This genome harbored 128 genes and encompassed 150 simple sequence repeats (SSRs). Through comparative analyses involving cp genomes from other Cyclolobeae (Amarathaceae) taxa, we observed that the K. ceratoides cp genome exhibited high conservation, with minor divergence events in protein-coding genes (PCGs) accD, matK, ndhF, ndhK, ycf1, and ycf2. Phylogenetic reconstructions delineated K. ceratoides as the sister taxon to Atriplex, Chenopodium, Dysphania, and Suaeda, thus constituting a robust clade. Intriguingly, nucleotide substitution ratios (Ka/Ks) between K. ceratoides and Dysphania species for ycf1 and ycf2 genes surpassed 1.0, indicating the presence of positive selection pressure on these loci. CONCLUSIONS: The findings of this study augment the genomic repository for the Amarathaceae family and furnish crucial molecular instruments for subsequent investigations into the ecological adaptation mechanisms of K. ceratoides within desert ecosystems.

Biotransformation of 5-methoxy-N-isopropyl-N-methyltryptamine by zebrafish and human liver microsome with high-resolution mass spectrometry.

To explore the metabolites of 5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT) and unveil its toxicological effects, we examined its metabolic profiles using zebrafish and human liver microsome models. Employing ultra-high-performance liquid chromatography Q Exactive hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-QE-HRMS), we analyzed samples from intoxicated zebrafish and human liver microsomes. In the zebrafish model, we identified a total of six metabolites. Primary phase I metabolic pathways involved N-Demethylation and Indole-hydroxylation reactions, while phase II metabolism included Glucoside conjugation directly, Glucoside conjugation after Indole-hydroxylation, and Sulfonation following Indole-hydroxylation. In the human liver microsome model, nine metabolites were generated. Major phase I metabolic pathways encompassed N-Demethylation, 5-O-Demethylation, and N-Depropylation, N-Oxidation, Indole-hydroxylation, N-Demethylation combined with Indole-hydroxylation, and 5-O-Methylation-carboxylation. Phase II metabolism involved Glucoside conjugation after Indole-hydroxylation, as well as Glucoside conjugation after 5-O-Demethylation. Proposed phase I metabolites, such as 5-MeO-MiPT-N-Demethylation (5-MeO-NiPT) and 5-MeO-MiPT-Indole-hydroxylation, alongside the phase II metabolite OH&Glucoside conjugation-5-MeO-MiPT, were identified as effective markers for screening 5-MeO-MiPT intake. This study systematically delineates the phase I and II metabolites of 5-MeO-MiPT, confirming their pathways through in vivo and in vitro extrapolation. Additionally, inclusion of the parent drug itself and OH&Glucoside conjugation-5-MeO-MiPT could serve as valuable confirmation tools.

USP31 serves as a potential biomarker for predicting prognosis and immune responses for clear cell renal cell carcinoma via single-cell and bulk RNA-sequencing.

BACKGROUND: Currently, there is no research available on the prognosis, potential effect and therapeutic value of USP31 in clear cell renal cell carcinoma (ccRCC). To address this gap, the present study aimed to shed light on its potential roles and possible mechanisms in ccRCC. METHODS: R software was utilized to conduct bioinformatics analyses with the data derived from The Cancer Genome Atlas (i.e. KIRC) and Gene Expression Omnibus datasets. The expression of USP31 in ccRCC was validated by a PCR. The independent prognostic ability of USP31 was evaluated by Cox regression analysis. We conducted gene set enrichment analysis (GSEA) to explore the potential USP31-related pathways. We also discussed the relationships between USP31 and immunity, by predicting its possible upstream transcription factors (TFs) by ChEA3. RESULTS: In ccRCC, USP31 demonstrated a high level of expression and this increased expression was correlated with a poor prognosis (p < 0.05). Through univariate and multivariate Cox regression analysis, USP31 was identified as an independent prognostic factor for ccRCC (p < 0.05). Furthermore, eight USP31-related pathways were identified by GSEA (p < 0.05). Moreover, USP31 was found to be associated with microsatellite instability, tumor microenvironment, a variety of immune cells and immune checkpoints and immune infiltration (p < 0.05). Additionally, Patients with high USP31 expression in ccRCC were shown to have better curative effects after immunotherapy (p < 0.05). Finally, we found that AR, USF1, MXI1 and CLOCK could be the potential upstream TFs of USP31. CONCLUSIONS: USP31 could serve as a potential biomarker for predicting both prognosis and immune responses, revealing its potential mechanisms of TF-USP31 mRNA networks in ccRCC.

Improved YOLOv7-Based Algorithm for Detecting Foreign Objects on the Roof of a Subway Vehicle.

Subway vehicle roofs must be inspected when entering and exiting the depot to ensure safe subway vehicle operations. This paper presents an improved method for detecting foreign objects on subway vehicle roofs based on the YOLOv7 algorithm. First, we capture images of foreign objects using a line-scan camera at the depot entrance and exit, creating a dataset of foreign roof objects. Subsequently, we address the shortcomings of the YOLOv7 algorithm by introducing the Ghost module, an improved weighted bidirectional feature pyramid network (WBiFPN), and the Wise intersection over union (WIoU) bounding-box regression loss function. These enhancements are incorporated to build the subway vehicle roof foreign object detection model based on the improved YOLOv7, which we refer to as YOLOv7-GBW. The experimental results demonstrate the practicality and usability of the proposed method. The analysis of the experimental results indicates that the YOLOv7-GBW algorithm achieves a detection accuracy of 90.29% at a speed of 54.3 frames per second (fps) with a parameter count of 15.51 million. The improved YOLOv7 model outperforms mainstream detection algorithms in terms of detection accuracy, speed, and parameter count. This finding confirms that the proposed method meets the requirements for detecting foreign objects on subway vehicle roofs.

A genome assembly for Orinus kokonorica provides insights into the origin, adaptive evolution and further diversification of two closely related grass genera.

Ancient whole-genome duplication (WGD) or polyploidization is prevalent in plants and has played a crucial role in plant adaptation. However, the underlying genomic basis of ecological adaptation and subsequent diversification after WGD are still poorly understood in most plants. Here, we report a chromosome-scale genome assembly for the genus Orinus (Orinus kokonorica as representative) and preform comparative genomics with its closely related genus Cleistogenes (Cleistogenes songorica as representative), both belonging to a newly named subtribe Orininae of the grass subfamily Chloridoideae. The two genera may share one paleo-allotetraploidy event before 10 million years ago, and the two subgenomes of O. kokonorica display neither fractionation bias nor global homoeolog expression dominance. We find substantial genome rearrangements and extensive structural variations (SVs) between the two species. With comparative transcriptomics, we demonstrate that functional innovations of orthologous genes may have played an important role in promoting adaptive evolution and diversification of the two genera after polyploidization. In addition, copy number variations and extensive SVs between orthologs of flower and rhizome related genes may contribute to the morphological differences between the two genera. Our results provide new insights into the adaptive evolution and subsequent diversification of the two genera after polyploidization.

The complexation of atmospheric Brown carbon surrogates on the generation of hydroxyl radical from transition metals in simulated lung fluid.

Atmospheric particulate matter (PM) poses great adverse effects through the production of reactive oxygen species (ROS). Various components in PM are acknowledged to induce ROS formation, while the interactions among chemicals remain to be elucidated. Here, we systematically investigate the influence of Brown carbon (BrC) surrogates (e.g., imidazoles, nitrocatechols and humic acid) on hydroxyl radical (OH) generation from transition metals (TMs) in simulated lung fluid. Present results show that BrC has an antagonism (interaction factor: 20-90 %) with Cu2+ in OH generation upon the interaction with glutathione, in which the concentrations of BrC and TMs influence the extent of antagonism. Rapid OH generation in glutathione is observed for Fe2+, while OH formation is very little for Fe3+. The compositions of antioxidants (e.g., glutathione, ascorbate, urate), resembling the upper and lower respiratory tract, respond differently to BrC and TMs (Cu2+, Fe2+ and Fe3+) in OH generation and the degree of antagonism. The complexation equilibrium constants and site numbers between Cu2+ and humic acid were further analyzed using fluorescence quenching experiments. Possible complexation products among TMs, 4-nitrocatechol and glutathione were also identified using quadropule-time-of-flight mass spectrometry. The results suggest atmospheric BrC widely participate in complexation with TMs which influence OH formation in the human lung fluid, and complexation should be considered in evaluating ROS formation mediated by ambient PM.

Precise Differentiation of Wobble-Type Allele via Ratiometric Design of a Ligase Chain Reaction-Based Electrochemical Biosensor for CYP2C19*2 Genotyping of Clinical Samples.

Due to the comparable stability between the perfect-base pair and the wobble-base pair, a precise differentiation of the wobble-type allele has remained a challenge, often leading to false results. Herein, we proposed a ligase chain reaction (LCR)-based ratiometric electrochemical DNA sensor, namely, R-eLCR, for a precise typing of the wobble-type allele, in which the traditionally recognized "negative" signal of wobble-base pair-mediated amplification was fully utilized as a "positive" one and a ratiometric readout mode was employed to ameliorated the underlying potential external influence and improved its detection accuracy in the typing of the wobble-type allele. The results showed that the ratio between current of methylene blue (IMB) and current of ferrocene (IFc) was partitioned in three regions and three types of wobble-type allele were thus precisely differentiated (AA homozygote: IMB/IFc > 2; GG homozygote: IMB/IFc < 1; GA heterozygote: 1 < IMB/IFc < 2); the proposed R-eLCR successfully discriminated the three types of CYP2C19*2 allele in nine cases of human whole blood samples, which was consistent with those of the sequencing method. These results evidence that the proposed R-eLCR can serve as an accurate and robust alternative for the identification of wobble-type allele, which lays a solid foundation and holds great potential for precision medicine.

Development and verification of a deep learning-based m6A modification model for clinical prognosis prediction of renal cell carcinoma.

BACKGROUND: The deep learning-based m6A modification model for clinical prognosis prediction of patients with renal cell carcinoma (RCC) had not been reported for now. In addition, the important roles of methyltransferase-like 14 (METTL14) in RCC have never been fully explored. METHODS: A high-level neural network based on deep learning algorithm was applied to construct the m6A-prognosis model. Western blotting, quantitative real-time PCR, immunohistochemistry and RNA immunoprecipitation were used for biological experimental verifications. RESULTS: The deep learning-based model performs well in predicting the survival status in 5-year follow-up, which also could significantly distinguish the patients with high overall survival risk in two independent patient cohort and a pan-cancer patient cohort. METTL14 deficiency could promote the migration and proliferation of renal cancer cells. In addition, our study also illustrated that METTL14 might participate in the regulation of circRNA in RCC. CONCLUSIONS: In summary, we developed and verified a deep learning-based m6A-prognosis model for patients with RCC. We proved that METTL14 deficiency could promote the migration and proliferation of renal cancer cells, which might throw light on the cancer prevention by targeting the METTL14 pathway.

A machine learning model based on MRI for the preoperative prediction of bladder cancer invasion depth.

OBJECTIVES: To construct and validate a prediction model based on full-sequence MRI for preoperatively evaluating the invasion depth of bladder cancer. METHODS: A total of 445 patients with bladder cancer were divided into a seven-to-three training set and test set for each group. The radiomic features of lesions were extracted automatically from the preoperative MRI images. Two feature selection methods were performed and compared, the key of which are the Least Absolute Shrinkage and Selection Operator (LASSO) and the Max Relevance Min Redundancy (mRMR). The classifier of the prediction model was selected from six advanced machine-learning techniques. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were applied to assess the efficiency of the models. RESULTS: The models with the best performance for pathological invasion prediction and muscular invasion prediction consisted of LASSO as the feature selection method and random forest as the classifier. In the training set, the AUC of the pathological invasion model and muscular invasion model were 0.808 and 0.828. Furthermore, with the mRMR as the feature selection method, the external invasion model based on random forest achieved excellent discrimination (AUC, 0.857). CONCLUSIONS: The full-sequence models demonstrated excellent accuracy for preoperatively predicting the bladder cancer invasion status. CLINICAL RELEVANCE STATEMENT: This study introduces a full-sequence MRI model for preoperative prediction of the depth of bladder cancer infiltration, which could help clinicians to recognise pathological features associated with tumour infiltration prior to invasive procedures. KEY POINTS: • Full-sequence MRI prediction model performed better than Vesicle Imaging-Reporting and Data System (VI-RADS) for preoperatively evaluating the invasion status of bladder cancer. • Machine learning methods can extract information from T1-weighted image (T1WI) sequences and benefit bladder cancer invasion prediction.

Transcriptome Screening of Long Noncoding RNAs and Their Target Protein-Coding Genes Unmasks a Dynamic Portrait of Seed Coat Coloration Associated with Anthocyanins in Tibetan Hulless Barley.

Many plants have the capability to accumulate anthocyanins for coloration, and anthocyanins are advantageous to human health. In the case of hulless barley (Hordeum vulgare L. var. nudum), investigation into the mechanism of anthocyanin formation is limited to the level of protein-coding genes (PCGs). Here, we conducted a comprehensive bioinformatics analysis to identify a total of 9414 long noncoding RNAs (lncRNAs) in the seed coats of purple and white hulless barley along a developmental gradient. Transcriptome-wide profiles of lncRNAs documented several properties, including GC content fluctuation, uneven length, a diverse range of exon numbers, and a wide variety of transcript classifications. We found that certain lncRNAs in hulless barley possess detectable sequence conservation with Hordeum vulgare and other monocots. Furthermore, both differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) were concentrated in the later seed development stages. On the one hand, DElncRNAs could potentially cis-regulate DEPCGs associated with multiple metabolic pathways, including flavonoid and anthocyanin biosynthesis in the late milk and soft dough stages. On the other hand, there was an opportunity for trans-regulated lncRNAs in the color-forming module to affect seed coat color by upregulating PCGs in the anthocyanin pathway. In addition, the interweaving of hulless barley lncRNAs and diverse TFs may function in seed coat coloration. Notably, we depicted a dynamic portrait of the anthocyanin synthesis pathway containing hulless barley lncRNAs. Therefore, this work provides valuable gene resources and more insights into the molecular mechanisms underlying anthocyanin accumulation in hulless barley from the perspective of lncRNAs, which facilitate the development of molecular design breeding in crops.

Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae.

Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 µg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1, acox, and pparα), which indicated enhanced ß-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1, atp5fa1, and mt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, and polg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.

China Glaucoma Treatment Pattern Study I-Primary Angle-Closure Glaucoma: protocol for a multicentre, retrospective, observational study.

INTRODUCTION: Primary angle-closure glaucoma (PACG) is a leading cause of irreversible blindness globally, and the number of patients with PACG rises every year. Yet, there is a lack of knowledge about the clinical characteristics, therapeutic options and profile of patients with PACG in China. Hence, we design the China Glaucoma Treatment Pattern Study Ⅰ-Primary Angle-Closure Glaucoma (Ch-GTPⅠ). The objective of this paper is to describe the design and methodology of Ch-GTP. The aim of this study is to characterise the profile and trend associated with initial PACG treatment for the last 10 years in China. METHODS: Ch-GTPⅠ is a national multicentre retrospective observational study that will randomly sample from 50 hospitals throughout China. Over 7000 patient records hospitalised for initial PACG treatment from 2011 to 2020 will be selected randomly. The data from electronic medical records will be uploaded to an encrypted online platform that will receive and collate data from all collaborating hospitals. Data abstraction and monitoring will be performed in a standardised manner by trained statisticians to ensure consistency. Systematic data cleaning will also be conducted by statisticians to ensure data integrity before final data storage. The outcomes will include four broad categories: (1) demographics, (2) clinical characteristics, (3) therapeutic strategies and procedures and (4) early outcomes at discharge. The demographic characteristics and early outcomes will be summarised using descriptive statistics. Comparative analyses of characteristics and treatment pattern changing trends for different regions and years will be used to test for significant differences (t-test or Mann-Whitney U test). ETHICS AND DISSEMINATION: The collaborating hospitals obtained local approval based on a standard ethics application from internal ethics committees or acknowledged an existent ethics approval of the leading institution with approval from internal ethics committees. Due to the retrospective nature, written informed consent from patients was waived by the ethics committee. The results will be published in academic journals and presented at national and international academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100054643.

Genomic divergence between two sister Medicago species triggered by the quaternary climatic oscillations on the Qinghai-Tibet plateau and northern China.

Speciation is a central topic in evolutionary biology. However, how genomic divergence originates and accumulates in the face of gene flow during ecological adaptation remains poorly understood. Closely related species that have adapted to distinct environments but inhabit some overlapping ranges provide an ideal system to evaluate this issue. Here, we combine population genomics and species distribution models (SDMs) to examine genomic divergences between two sister plant species, Medicago ruthenica and M. archiducis-nicolai, that occur in northern China and the northeast Qinghai-Tibet Plateau, respectively, with overlapping distributions in the border of the two regions. M. ruthenica and M. archiducis-nicolai are well-delimited based on population genomic data, although hybrids exist in sympatric sampling locations. Coalescent simulations and SDMs suggest that the two species diverged from each other in the Quaternary but have been in continuous contact with gene flow occurring between the two species since then. We also discovered positive selection signatures associated with genes both outside and within genomic islands in both species that are probably involved in adaptations to arid and high-altitude environments. Our findings provide insights into how natural selection and climatic changes in the Quaternary initiated and maintained interspecific divergence of these two sister species.

A comparative study of cognitive functions between schizophrenia and obsessive-compulsive disorder.

Background: Schizophrenia (SZ) and obsessive-compulsive disorder (OCD) are closely linked, have a high comorbidity rate, and their differential diagnosis is challenging in clinic. Some studies have found common cognitive deficits in some domains between them. The goal of this research was to compare the cognitive functions of SZ and OCD in order to offer a clinical foundation for differential diagnosis and treatment of the two disorders. Methods: A control design was used in this study, which comprised 61 patients with SZ, 60 individuals with OCD, and 51 healthy controls (HC). We assessed patients' cognitive functions by testing six domains, including visual learning, reasoning and problem solving, verbal learning, attention/vigilance, speed of processing and working memory. Results: The results showed that patients with SZ had cognitive impairments in all areas except attention/vigilance, while patients with OCD only had cognitive impairment in reasoning and problem-solving. Overall, patients with SZ did not perform as well as patients with OCD in all domains. Conclusions: In terms of neurocognition, both of SZ and OCD patients have defects in reasoning and problem solving. In addition to this, SZ patients also performed worse than HC in other areas such as speed of processing, working memory, verbal learning and visual learning. On the overall level, cognitive performance is better in OCD patients than in SZ patients. The field of reasoning and problem solving can be used as a new goal to study the relationship and treatment strategies between them in the future.

Nucleic Acid Amplification by Template-Dominated Click Chemistry for Ultrasensitive DNA/RNA Detection on an Electrochemical Readout Platform.

As an enzyme-free exponential nucleic acid amplification method, the click chemistry-mediated ligation chain reaction (ccLCR) has shown great prospects in the molecular diagnosis. However, the current optics-based ccLCR is challenged by remarkable nonspecific amplification, severely hindering its future application. This study demonstrated that the severe nonspecific amplification was generated probably due to high random collision in the high DNA probe concentration (µM level). To solve this hurdle, a nucleic acid template-dominated ccLCR was constructed using nM-level DNA probes and read on an electrochemical platform (cc-eLCR). Under the optimal conditions, the proposed cc-eLCR detected a low-level nucleic acid target (1 fM) with a single-base resolution. Furthermore, this assay was applied to detect the target of interest in cell extracts with a satisfactory result. The proposed cc-eLCR offers huge possibility for click chemistry-mediated enzyme-free exponential nucleic acid amplification in the application of medical diagnosis and biomedical research.