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Abstract China has experienced successive waves of dengue epidemics over the past decade. Nationwide data on 95,339 dengue cases, 89 surveillance sites for mosquito density and population mobility between 337 cities during 2013-20 were extracted. Weekly dengue time series including time trends and harmonic terms were fitted using seasonal regression models, and the amplitude and peak timing of the annual and semiannual cycles were estimated. A data-driven model-inference approach was used to simulate the epidemic at city-scale and estimate time-evolving epidemiological parameters. We found that the geographical distribution of dengue cases was expanding, and the main imported areas as well as external sources of imported cases changed. Dengue cases were predominantly concentrated in southern China and it exhibited an annual peak of activity, typically peaking in September. The annual amplitude of dengue epidemic varied with latitude (F = 19.62, P = 0.0001), mainly characterizing by large in southern cities and small in northern cities. The effective reproduction number R eff across cities is commonly greater than 1 in several specific months from July to November, further confirming the seasonal fluctuations and spatial heterogeneity of dengue epidemics. The results of this national study help to better informing interventions for future dengue epidemics in China.

Abstract Background Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. Methods In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. Results The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. Conclusions Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Abstract Milk protein content is an important index to evaluate the quality and nutrition of milk. Accumulating evidence suggests that microRNAs (miRNAs) play important roles in bovine lactation, but little is known regarding the cross-kingdom regulatory roles of plant-derived exogenous miRNAs (xeno-miRNAs) in milk protein synthesis, particularly the underlying molecular mechanisms. The purpose of this study was to explore the regulatory mechanism of alfalfa-derived xeno-miRNAs on proliferation and milk protein synthesis in bovine mammary epithelial cells (BMECs). Our previous study showed that alfalfa miR159a (mtr-miR159a, xeno-miR159a) was highly expressed in alfalfa, and the abundance of mtr-miR159a was significantly lower in serum and whey from high-protein-milk dairy cows compared with low-protein-milk dairy cows. In this study, mRNA expression was detected by real-time quantitative PCR (qRT-PCR), and casein content was evaluated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis were detected using the cell counting kit 8 (CCK-8) assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, western blot, and flow cytometry. A dual-luciferase reporter assay was used to determine the regulation of Protein Tyrosine Phosphatase Receptor Type F (PTPRF) by xeno-miR159a. We found that xeno-miR159a overexpression inhibited proliferation of BMEC and promoted cell apoptosis. Besides, xeno-miR159a overexpression decreased β-casein abundance, and increased α-casein and κ-casein abundance in BMECs. Dual-luciferase reporter assay result confirmed that PTPRF is a target gene of xeno-miR159a. These results provide new insights into the mechanism by which alfalfa-derived miRNAs regulate BMECs proliferation and milk protein synthesis.

Abstract BackgroundPrior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.52.5 ObjectiveThis study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 MethodsThis cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.52.52.5 ResultsA total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-μg/m32.52.5 ConclusionsPM2.52.5

Objective It was shown that microRNAs (miRNAs) play an important role in milk protein synthesis. However, the post-transcriptional regulation of casein expression by exogenous miRNA (xeno-miRNAs) in ruminants remains unclear. This study explores the regulatory roles of alfalfa xeno-miR162 on casein synthesis in bovine mammary epithelial cells (bMECs). Methods The effects of alfalfa xenomiR-162 and G protein subunit gamma 11 (GNG11) on proliferation and milk protein metabolism of bMECs were detected by 5-Ethynyl-2′-Deoxyuridine (EdU) staining, flow cytometry, cell counting kit-8 (CCK-8), enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Dual-luciferase reporter assay was used to verify the targeting relationship between GNG11 and xenomiR-162. Results Results showed that over-expression of xenomiR-162 inhibited cell proliferation but promoted apoptosis, which also up-regulated the expression of several casein coding genes, including CSN1S1, CSN1S2, and CSN3, while decreasing the expression of CSN2. Furthermore, the targeting relationship between GNG11 and xenomiR-162 was determined, and it was confirmed that GNG11 silencing also inhibited cell proliferation but promoted apoptosis and reduced the expression of casein coding genes and genes related to the mammalian target of rapamycin (mTOR) pathway. Conclusion Alfalfa xenomiR-162 appears to regulate bMECs proliferation and milk protein synthesis via GNG11 in the mTOR pathway, suggesting that this xeno-miRNA could be harnessed to modulate CSN3 expression in dairy cows, and increase κ-casein contents in milk.

Highlights The latest advancements in Cu-based catalysts for photocatalytic and electrocatalytic CO2 reduction into C2+ products are reported. The relationship between the Cu surfaces and their efficiency in photocatalytic and electrocatalytic CO2 reduction is emphasized. The opportunities and challenges associated with Cu-based materials in the CO2 catalytic reduction applications are presented.

Abstract Background The cotton industry suffers significant yield losses annually due to Verticillium wilt, which is considered the most destructive disease affecting the crop. However, the precise mechanisms behind this disease in cotton remain largely unexplored. Methods Our approach involved utilizing transcriptome data from G. australe which was exposed to Verticillium dahliae infection. From this data, we identified ethylene-responsive factors and further investigated their potential role in resistance through functional validations via Virus-induced gene silencing (VIGS) in cotton and overexpression in Arabidopsis. Results A total of 23 ethylene response factors (ERFs) were identified and their expression was analyzed at different time intervals (24 h, 48 h, and 72 h post-inoculation). Among them, GauERF105 was selected based on qRT-PCR expression analysis for further investigation. To demonstrate the significance of GauERF105, VIGS was utilized, revealing that suppressing GauERF105 leads to more severe infections in cotton plants compared to the wild-type. Additionally, the silenced plants exhibited reduced lignin deposition in the stems compared to the WT plants, indicating that the silencing of GauERF105 also impacts lignin content. The overexpression of GauERF105 in Arabidopsis confirmed its pivotal role in conferring resistance against Verticillium dahliae infection. Our results suggest that WT possesses higher levels of the oxidative stress markers MDA and H2O2 as compared to the overexpressed lines. In contrast, the activities of the antioxidant enzymes SOD and POD were higher in the overexpressed lines compared to the WT. Furthermore, DAB and trypan staining of the overexpressed lines suggested a greater impact of the disease in the wild-type compared to the transgenic lines. Conclusions Our findings provide confirmation that GauERF105 is a crucial candidate in the defense mechanism of cotton against Verticillium dahliae invasion, and plays a pivotal role in this process. These results have the potential to facilitate the development of germplasm resistance in cotton.

Abstract Background The cyclic nucleotide-gated channel (CNGC) gene family plays a significant role in the uptake of both essential and toxic cations, and has a role in enhancing tolerance to various forms of abiotic stresses as well as the modulation of the heavy metal toxicity to plant through the absorption of heavy metals. Results A complete genome-wide identification and functional characterization of the cotton CNGC genes was carried out, in which 55, 28, and 29 CNGC genes were identified in Gossypium hirsutum, G. raimondii, and G. arboreum, respectively. The protein encoded by the CNGC genes exhibited GRAVY value below zero, indicating their hydrophilic property. CNGC genes were unevenly distributed in 19 out of 26 chromosomes, in which the highest density were observed on Ah05, with 8 genes. High gene coverage was observed among the diploid cotton species, with CNGC genes mapped on all A chromosomes and on 11 out of 13 of D chromosomes. The majority of CNGC proteins were localized in the endoplasmic reticulum, nucleus, and plasma membrane. Gene expression analysis revealed the up-regulation of Gh_A01G0520 (CNGC4) and Gh_D13G1974 (CNGC5) across various forms of abiotic stresses. Moreover, down-regulation of Gh_A01G0520 (CNGC4) and Gh_D13G1974 (CNGC5) in CNGC s silenced plants caused the significantly reduced ability to tolerate drought and salt stresses. All CNGCs silenced plants were recorded to have significantly low content of antioxidants but relatively higher content of oxidant, including MDA and H2O2. Furthermore, SPAD, CMS (cell membrane stability), ELWL (excised leaf water loss), SDW (shoot dry matter weight), and RDW (root dry matter weight) were all lower in CNGCs silenced plants compared with the wild type plants. Conclusion Significant reduction in antioxidant content and negative effects of physiological and morphological characters in CNGCs silenced plants has revealed the novel role of CNGC genes in enhancing cell integrity under abiotic stress conditions. These results provide vital information that will expand our understanding of the CNGC gene family in cotton and other plants, thus promoting the integration of these genes in the development of the environmental resilient plants.

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values

Summary: The 5′-deoxyadenosine deaminase (DADD), a member of the amidohydrolase family regulates biological purine metabolism. In this study, bioinformatic analysis, overexpression and knockdown of GhdadD gene were detected to identify its potential role in drought and salt stress tolerance. The results revealed that GhdadD was induced by ABA, Auxin, MBS and light responsive elements. In transgenic Arabidopsis, seed germination rate and root length were increased under drought or salt stress. GhdadD overexpressed seedlings resulted in higher plant height, less leaf damage and lower ion permeability. The expression of osmotic stress and ABA-responsive genes were up regulated. While in GhdadD-silenced cotton seedlings, CAT, SOD activity and soluble sugar content were reduced, MDA content was increased, and the stoma opening was depressed under drought or salt stress. Some osmics stress marker genes were also up regulated. These data indicating that GhdadD enhanced plant resistance to drought and salt stress through ABA pathways.

Abstract Background Surgical Nursing is a core subject for nursing undergraduates that requires active and effective learning strategies to cultivate students’ autonomous learning competencies and critical thinking. The effects of BOPPPS (Bridge-in, Objectives, Pretest, Participatory Learning, Post-test and Summary) model combined with team-based learning (TBL) have rarely been explored in Surgical Nursing courses. Objective To explore the effects of BOPPPS combined with TBL in Surgical Nursing for nursing undergraduates. Methods A mixed research method of quasi-experimental study design and descriptive qualitative research was used. The control group included 27 nursing undergraduates who had finished the Surgical Nursing course using traditional learning. The experimental group included 36 nursing undergraduates were enrolled in to receive the Surgical Nursing course in the teaching mode of BOPPPS combined with TBL. The quantitative data of students’ Surgical Nursing final scores, autonomous learning competencies and critical thinking ability of the two groups were collected and compared by t-test. Qualitative results were obtained through semi-structured interviews and data were analyzed by thematic analysis method. Results Compared with the traditional learning mode, BOPPPS combined with TBL significantly improved nursing students’ final examination scores, autonomous learning competencies and critical thinking ability (p

Abstract Background Plant pollen has diverse morphological characteristics that can be consistently passed down from generation to generation. Information on pollen morphology is thus immensely important for plant classification and identification. In the genus Gossypium, however, in-depth research on pollen morphology is lacking, with only few reports on limited cotton species. To evaluate the diversity of pollen in Gossypium, we therefore conducted a comprehensive analysis of the pollen morphology of 33 cotton species and varieties using scanning electron microscopy. Results The 33 analyzed cotton samples exhibited common pollen morphological features, including spherical shapes, radial symmetry, echination, panporation, and operculation, while the pollen size, spine shape, spine density and length showed distinctive features. Pollen size varied significantly among species, with diameters ranging from 62.43 μm in G. harknessii to 103.41 μm in G. barbadense. The exine had an echinate sculptural texture, and spines were mostly conical or sharply conical but occasionally rod-like. Spine density varied from 173 in G. incanum to 54 in G. gossypioides, while spine length ranged from 3.53 μm in G. herbaceum to 9.47 μm in G. barbadense. In addition, the 33 cotton species and varieties were grouped at a genetic distance of 3.83 into three clusters. Cluster I comprised five allotetraploid AD-genome cotton species, four D-genome species, and one K-genome species. Cluster II included 13 diploid species from A, B, D, E, and G genomes, whereas Cluster III only consisted one E-genome species G. incanum. Conclusions Although pollen characteristics alone are not enough to resolve taxonomic and systematic relationships within the genus Gossypium, our results add to knowledge on palynomorphology and contribute to phenological information on these taxa. Our findings should aid future systematic and phylogenetic studies of the Gossypium genus.

Abstract Background Current climate change scenarios are posing greater threats to the growth and development of plants. Thus, significant efforts are required that can mitigate the negative effects of drought on the cotton plant. GDSL esterase/lipases can offer an imperative role in plant development and stress tolerance. However, thesystematic and functional roles of the GDSL gene family, particularly in cotton under water deficit conditions have not yet been explored. Results In this study, 103, 103, 99, 198, 203, 239, 249, and 215 GDSL proteins were identified in eight cotton genomes i.e., Gossypium herbaceum (A1), Gossypium arboretum (A2), Gossypium raimondii (D5), Gossypium hirsutum (AD1), Gossypium barbadense (AD2), Gossypium tomentosum (AD3), Gossypium mustelinum (AD4), Gossypium darwinii (AD5), respectively. A total of 198 GDSL genes of Gossypium hirsutum were divided into eleven clades using phylogenetic analysis, and the number of GhirGDSL varied among different clades. The cis-elements analysis showed that GhirGDSL gene expression was mainly related to light, plant hormones, and variable tense environments. Combining the results of transcriptome and RT-qPCR, GhirGDSL26 (Gh_A01G1774), a highly up-regulated gene, was selected for further elucidating its tole in drought stress tolerance via estimating physiological and biochemical parameters. Heterologous expression of the GhirGDSL26 gene in Arabidopsis thaliana resulted in a higher germination and survival rates, longer root lengths, lower ion leakage and induced stress-responsive genes expression under drought stress. This further highlighted that overexpressed plants had a better drought tolerance as compared to the wildtype plants. Moreover, 3, 3’-diaminobenzidine (DAB) and Trypan staining results indicated reduced oxidative damage, less cell membrane damage, and lower ion leakage in overexpressed plants as compared to wild type. Silencing of GhirGDSL26 in cotton via VIGS resulting in a susceptible phenotype, higher MDA and H2O2 contents, lower SOD activity, and proline content. Conclusion Our results demonstrated that GhirGDSL26 plays a critical role in cotton drought stress tolerance. Current findings enrich our knowledge of GDSL genes in cotton and provide theoretical guidance and excellent gene resources for improving drought tolerance in cotton.

Salinity is a major threat to the yield and productivity of cotton seedlings. In the present study, we developed a BC2F2 population of cotton plants from Gossypium darwinii (5–7) and Gossypium hirsutum (CCRI 12–4) salt-susceptible parents to identify salt-resistant candidate genes. The Illumina HiSeq™ strategy was used with bulked segregant analysis. Salt-resistant and salt-susceptible DNA bulks were pooled by using 30 plants from a BC2F2 population. Next-generation sequencing (NGS) technology was used for the sequencing of parents and both bulks. Four significant genomic regions were identified: the first genomic region was located on chromosome 18 (1.86 Mb), the second and third genomic regions were on chromosome 25 (1.06 Mb and 1.94 Mb, respectively), and the fourth was on chromosome 8 (1.41 Mb). The reads of bulk1 and bulk2 were aligned to the G. darwinii and G. hirsutum genomes, respectively, leading to the identification of 20,664,007 single-nucleotide polymorphisms (SNPs) and insertions/deletions (indels). After the screening, 6,573 polymorphic markers were obtained after filtration of the candidate regions. The SNP indices in resistant and susceptible bulks and Δ(SNP-index) values of resistant and susceptible bulks were measured. Based on the higher Δ(SNP-index) value, six effective polymorphic SNPs were selected in a different chromosome. Six effective SNPs were linked to five candidate genes in four genomic regions. Further validation of these five candidate genes was carried out using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), resulting in an expression profile that showed two highly upregulated genes in the salt-tolerant species G. darwinii, i.e., Gohir.D05G367800 and Gohir.D12G239100; however, the opposite was shown in G. hirsutum, for which all genes, except one, showed partial expression. The results indicated that Gohir.D05G367800 and Gohir.D12G239100 may be salt-tolerant genes. We are confident that this study could be helpful for the cloning, transformation, and development of salt-resistant cotton varieties.

Abstract Text generation is a key tool in natural language applications. Generating texts which could express rich ideas through several sentences needs a structured representation of their content. Many works utilize graph-based methods for graph-to-text generation, like knowledge-graph-to-text generation. However, generating texts from knowledge graph still faces problems, such as repetitions and the entity information is not fully utilized in the generated text. In this paper, we focus on knowledge-graph-to-text generation, and develop a multi-level entity fusion representation (MEFR) model to address the above problems, aiming to generate high-quality text from knowledge graph. Our model introduces a fusion mechanism, which is capable of aggregating node representations from word level and phrase level to obtain rich entity representations of the knowledge graph. Then, Graph Transformer is adopted to encode the graph and outputs contextualized node representations. Besides, we develop a vanilla beam search-based comparison mechanism during decoding procedure, which further considers similarity to reduce repetitive information of the generated text. Experimental results show that the proposed MEFR model could effectively improve generation performance, and outperform other baselines on AGENDA and WebNLG datasets. The results also demonstrate the importance to further explore information contained in knowledge graph.

Abstract Background Crops face several environmental stresses (biotic and abiotic), thus resulting in severe yield losses. Around the globe abiotic stresses are the main contributors of plant damages, primarily drought and salinity. Many genes and transcription factors are involved in abiotic and biotic stress responses. NAC TF (Transcription Factors) improves tolerance to stresses by controlling the physiological and enzyme activities of crops. Results In current research, GhNAC072 a highly upregulated TF in RNA-Seq was identified as a hub gene in the co-expression network analysis (WGCNA). This gene was transformed to Arabidopsis thaliana to confirm its potential role in drought and salt stress tolerance. Significant variations were observed in the morpho-physiological traits with high relative leaf water contents, chlorophyll contents, higher germination and longer root lengths of the overexpressed lines and low excised leaf loss and ion leakage as compared to the wildtype plants. Besides, overexpressed lines have higher amounts of antioxidants and low oxidant enzyme activities than the wildtype during the period of stress exposure. Conclusions In summary, the above analysis showed that GhNAC072 might be the true candidate involved in boosting tolerance mechanisms under drought and salinity stress.

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of heart failure (HF) than those without NAFLD. However, the prognostic impact of NAFLD in HF is still controversial. This meta-analysis aimed to explore the association between NAFLD and the risk of adverse outcomes in patients with HF.MethodsWe searched multiple electronic databases (Embase, PubMed, and Google Scholar) for potentially related studies up to June 30, 2022. Cohort studies reported multivariable adjusted relative risks and 95% confidence intervals (CIs) of adverse outcomes in HF patients with NAFLD comparing those without NAFLD were included for analysis.ResultsA total of six studies involving 12,374 patients with HF were included for analysis, with a median follow-up duration of 2.5 years. The pooled analysis showed that HF patients with NAFLD were associated with a significantly increased risk of major composite adverse outcomes (HR 1.61, 95% CI 1.25-2.07), all-cause mortality (HR 1.66, 95% CI 1.39-1.98), and HF hospitalization or re-hospitalization (HR 1.71, 95% CI 1.03-2.86).ConclusionNAFLD is associated with a worse prognosis in patients with HF. Effective screening and treatment strategies are needed to improve the prognosis in HF patients with NAFLD.

Abstract Background Osteoarthritis (OA) is the most common joint disease, and is most frequently seen in the knees. However, there is no effective therapy to relieve the progression of knee OA. Metformin is a safe, well-tolerated oral medication that is extensively used as first-line therapy for type 2 diabetes. Previous observational studies and basic researches suggested that metformin may have protective effects on knee OA, which needs to be verified by clinical trials. This study, therefore, aims to examine the effects of metformin versus placebo on knee cartilage volume loss and knee symptoms in overweight knee OA patients by a randomized controlled trial over 24 months. Methods This protocol describes a multicenter, randomized, double-blind, and placebo-controlled clinical trial aiming to recruit 262 overweight knee OA patients. Participants will be randomly allocated to the two arms of the study, receiving metformin hydrochloride sustained-release tablets or identical inert placebo for 24 months (start from 0.5 g/day for the first 2 weeks, and increase to 1 g/day for the second 2 weeks, and further increase to 2 g/day for the remaining period if tolerated). Primary outcomes will be changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 24 months. Secondary outcomes will be changes in visual analogue scale (VAS) knee pain, tibiofemoral cartilage defects, effusion-synovitis volume, and tibiofemoral bone marrow lesions maximum size over 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per-protocol analyses will be performed as the secondary analyses. Discussion If metformin is proved to slow knee cartilage volume loss and to relieve knee symptoms among overweight knee OA patients, it will have the potential to become a disease modifying drug for knee OA. Metformin is a convenient intervention with low cost, and its potential effects on slowing down the structural progression and relieving the symptoms of knee OA would effectively reduce the disease burden worldwide. Trial registration ClinicalTrials. gov NCT05034029 . Registered on 30 Sept 2021.

Abstract Background Cotton is a valuable economic crop and the main significant source of natural fiber for textile industries globally. The effects of drought and salt stress pose a challenge to strong fiber and large-scale production due to the ever-changing climatic conditions. However, plants have evolved a number of survival strategies, among them is the induction of various stress-responsive genes such as the ribosomal protein large (RPL) gene. The RPL gene families encode critical proteins, which alleviate the effects of drought and salt stress in plants. In this study, comprehensive and functional analysis of the cotton RPL genes was carried out under drought and salt stresses. Results Based on the genome-wide evaluation, 26, 8, and 5 proteins containing the RPL14B domain were identified in Gossypium hirsutum, G. raimondii, and G. arboreum, respectively. Furthermore, through bioinformatics analysis, key cis-regulatory elements related to RPL14B genes were discovered. The Myb binding sites (MBS), abscisic acid-responsive element (ABRE), CAAT-box, TATA box, TGACG-motif, and CGTCA-motif responsive to methyl jasmonate, as well as the TCA-motif responsive to salicylic acid, were identified. Expression analysis revealed a key gene, Gh_D01G0234 (RPL14B), with significantly higher induction levels was further evaluated through a reverse genetic approach. The knockdown of Gh_D01G0234 (RPL14B) significantly affected the performance of cotton seedlings under drought/salt stress conditions, as evidenced by a substantial reduction in various morphological and physiological traits. Moreover, the level of the antioxidant enzyme was significantly reduced in VIGS-plants, while oxidant enzyme levels increased significantly, as demonstrated by the higher malondialdehyde concentration level. Conclusion The results revealed the potential role of the RPL14B gene in promoting the induction of antioxidant enzymes, which are key in oxidizing the various oxidants. The key pathways need to be investigated and even as we exploit these genes in the developing of more stress-resilient cotton germplasms.

Abstract Background Cyclin-dependent kinases (CDKs) are protein kinases regulating important cellular processes such as cell cycle and transcription. Many CDK genes also play a critical role during adipogenic differentiation, but the role of CDK gene family in regulating bovine adipocyte differentiation has not been studied. Therefore, the present study aims to characterize the CDK gene family in bovine and study their expression pattern during adipocyte differentiation. Results We performed a genome-wide analysis and identified a number of CDK genes in several bovine species. The CDK genes were classified into 8 subfamilies through phylogenetic analysis. We found that 25 bovine CDK genes were distributed in 16 different chromosomes. Collinearity analysis revealed that the CDK gene family in Bos taurus is homologous with Bos indicus, Hybrid-Bos taurus, Hybrid Bos indicus, Bos grunniens and Bubalus bubalis. Several CDK genes had higher expression levels in preadipocytes than in differentiated adipocytes, as shown by RNA-seq analysis and qPCR, suggesting a role in the growth of emerging lipid droplets. Conclusion In this research, 185 CDK genes were identified and grouped into eight distinct clades in Bovidae, showing extensively homology. Global expression analysis of different bovine tissues and specific expression analysis during adipocytes differentiation revealed CDK4, CDK7, CDK8, CDK9 and CDK14 may be involved in bovine adipocyte differentiation. The results provide a basis for further study to determine the roles of CDK gene family in regulating adipocyte differentiation, which is beneficial for beef quality improvement.

Background and aims: Recent research has associated non-alcoholic fatty liver disease (NAFLD) with an increased risk of atherosclerotic cardiovascular disease. Previous studies that evaluated the association between NAFLD and risk of heart failure (HF) yielded inconsistent results, however. This meta-analysis aimed to evaluate the association between NAFLD and the risk of HF. Methods: We searched multiple electronic databases, including PubMed, Google Scholar, Embase and Web of Science for potential studies published from inception until 30 October 2021. Cohort studies reported multivariable-adjusted risks of incident HF in NAFLD patients comparing those without NAFLD were included. Results: Six cohort studies comprising 10,979,967 participants (women = 55.5%) were included in the study. The median prevalence of NAFLD in these studies was 22.2%. During a median follow-up duration of 7.0 years, 92,915 HF cases were detected. In the unadjusted model, patients with NAFLD had a greater risk of incident HF [random-effect hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.25–1.75, I 2 = 99%], compared with those without NAFLD. After multivariable adjustment of confounding risk factors, NAFLD was still linked with a higher risk of HF incidence (random-effect HR = 1.36, 95% CI = 1.16–1.58, I 2 = 98%). The risk of HF was increased not only in patients with progressive NAFLD severity but also in those with simple steatosis. The absolute risk difference of HF in NAFLD patients compared with those without NAFLD was 11.0 (95% CI = 4.9–17.7) per 10,000 person-years after multivariable adjustment. Conclusion: This meta-analysis suggests that NAFLD may be associated with an increased risk of incident HF. Owing to the high heterogeneity of the published studies, however, further high-quality studies are still needed.

The youngest generation of students prefers a more active learning style. Sandwich teaching may suit their learning style by alternating between active individual learning and passive collective learning. Sandwich teaching has been rarely applied to the Community Nursing Course for nursing students, and its teaching effects on this course remain unclear. This study applied Sandwich teaching to the Community Nursing Course for Chinese nursing undergraduates and investigated its effects on students' critical thinking, self-learning ability, course experience, and academic performance. This is a quasi-experimental study with 72 Chinese nursing undergraduates. Students receiving traditional teaching were enrolled in the control group (n = 36), and those who received Sandwich teaching were recruited into the experimental group (n = 36). Both groups received the 12-week, 90-min Community Nursing Course. Our main outcome variable, including students' critical thinking, self-learning ability, and course experience, was assessed by specific questionnaire. The paired t-tests were applied to compare the differences of the same group in the pre-test and the post-test, and the independent-sample t-tests were used to compare the differences between the two groups. We observed that nursing students' critical thinking ability and self-learning ability were significantly improved after receiving Sandwich teaching. Students' course experience of Sandwich teaching was significantly better than that of traditional teaching. The final exam score in the experimental group was not significantly higher than that in the control group. These results suggest that Sandwich teaching in Community Nursing Course improved Chinese nursing undergraduates' critical thinking, self-learning ability, and course experience, but failed in improving academic performance.

Objective T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control.Methods Peripheral blood CD4+ and CD8+ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed.Results There was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28+ and CD28− cells in CD4+ T cells was observed in patients with SLE. We found that the expanded CD4+CD28− T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4+CD28− T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4+CD28+ T cells and Treg cells in this study. Increased CD8+HLADR+ T cell and CD8+CD38+HLADR+ T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8+ T cells in SLE. Additionally, we found that CD8+CD38+HLADR+ T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4+ CXCR5−PD1+ T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study.Conclusion The proportions of CD4+CD28− T cells, CD4+CXCR5−PD1+ T cells, CD8+HLADR+ T cells and CD8+CD38+HLADR+ T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.

Lint percentage is one of the most essential yield components and an important economic index for cotton planting. Improving lint percentage is an effective way to achieve high-yield in cotton breeding worldwide, especially upland cotton (Gossypium hirsutum L.). However, the genetic basis controlling lint percentage has not yet been systematically understood. Here, we performed a genome-wide association mapping for lint percentage using a natural population consisting of 189 G. hirsutum accessions (188 accessions of G. hirsutum races and one cultivar TM-1). The results showed that 274 single-nucleotide polymorphisms (SNPs) significantly associated with lint percentage were detected, and they were distributed on 24 chromosomes. Forty-five SNPs were detected at least by two models or at least in two environments, and their 5 Mb up- and downstream regions included 584 makers related to lint percentage identified in previous studies. In total, 11 out of 45 SNPs were detected at least in two environments, and their 550 Kb up- and downstream region contained 335 genes. Through RNA sequencing, gene annotation, qRT-PCR, protein–protein interaction analysis, the cis-elements of the promotor region, and related miRNA prediction, Gh_D12G0934 and Gh_A08G0526 were selected as key candidate genes for fiber initiation and elongation, respectively. These excavated SNPs and candidate genes could supplement marker and gene information for deciphering the genetic basis of lint percentage and facilitate high-yield breeding programs of G. hirsutum ultimately.

Abstract Background Cotton is an important commercial crop for being a valuable source of natural fiber. Its production has undergone a sharp decline because of abiotic stresses, etc. Drought is one of the major abiotic stress causing significant yield losses in cotton. However, plants have evolved self-defense mechanisms to cope abiotic factors like drought, salt, cold, etc. The evolution of stress responsive transcription factors such as the trihelix, a nodule-inception-like protein (NLP), and the late embryogenesis abundant proteins have shown positive response in the resistance improvement to several abiotic stresses. Results Genome wide identification and characterization of the effects of Light-Harvesting Chloro a/b binding (LHC) genes were carried out in cotton under drought stress conditions. A hundred and nine proteins encoded by the LHC genes were found in the cotton genome, with 55, 27, and 27 genes found to be distributed in Gossypium hirsutum, G. arboreum, and G. raimondii, respectively. The proteins encoded by the genes were unevenly distributed on various chromosomes. The Ka/Ks (Non-synonymous substitution rate/Synonymous substitution rate) values were less than one, an indication of negative selection of the gene family. Differential expressions of genes showed that majority of the genes are being highly upregulated in the roots as compared with leaves and stem tissues. Most genes were found to be highly expressed in MR-85, a relative drought tolerant germplasm. Conclusion The results provide proofs of the possible role of the LHC genes in improving drought stress tolerance, and can be explored by cotton breeders in releasing a more drought tolerant cotton varieties.

Trichomes protect plants against insects, microbes, herbivores, and abiotic damages and assist seed dispersal. The function of CPR5 genes have been found to be involved in the trichome development but the research on the underlying genetic and molecular mechanisms are extremely limited. Herein, genome wide identification and characterization of CPR5 genes was performed. In total, 26 CPR5 family members were identified in Gossypium species. Phylogenetic analysis, structural characteristics, and synteny analysis of CPR5s showed the conserved evolution relationships of CPR5. The promoter analysis of CPR5 genes revealed hormone, stress, and development-related cis-elements. Gene ontology (GO) enrichment analysis showed that the CPR5 genes were largely related to biological regulation, developmental process, multicellular organismal process. Protein-protein interaction analysis predicted several trichome development related proteins (SIM, LGO, and GRL) directly interacting with CPR5 genes. Further, nine putative Gossypium-miRNAs were also identified, targeting Gossypium CPR5 genes. RNA-Seq data of G. arboreum (with trichomes) and G. herbaceum (with no trichomes) was used to perform the co-expression network analysis. GheCPR5.1 was identified as a hub gene in a co-expression network analysis. RT-qPCR of GheCPR5.1 gene in different tissues suggests that this gene has higher expressions in the petiole and might be a key candidate involved in the trichome development. Virus induced gene silencing of GheCPR5.1 (Ghe02G17590) confirms its role in trichome development and elongation. Current results provide proofs of the possible role of CPR5 genes and provide preliminary information for further studies of GheCPR5.1 functions in trichome development.

Drought seriously threats the growth and development of Gossypium hirsutum L. To dissect the genetic basis for drought tolerance in the G. hirsutum L. germplasm, a population, consisting of 188 accessions of G. hirsutum races and a cultivar (TM-1), was genotyped using the Cotton80KSNP biochip, and 51,268 high-quality single-nucleotide polymorphisms (SNPs) were obtained. Based on the phenotypic data of eight drought relative traits from four environments, we carried out association mapping with five models using GAPIT software. In total, thirty-six SNPs were detected significantly associated at least in two environments or two models. Among these SNPs, 8 and 28 (including 24 SNPs in 5 peak regions) were distributed in the A and D subgenome, respectively; eight SNPs were found to be distributed within separate genes. An SNP, TM73079, located on chromosome D10, was simultaneously associated with leaf fresh weight, leaf wilted weight, and leaf dry weight. Another nine SNPs, TM47696, TM33865, TM40383, TM10267, TM59672, TM59675, TM59677, TM72359, and TM72361, on chromosomes A13, A10, A12, A5, D6, and D9, were localized within or near previously reported quantitative trait loci for drought tolerance. Moreover, 520 genes located 200 kb up- and down-stream of 36 SNPs were obtained and analyzed based on gene annotation and transcriptome sequencing. The results showed that three candidate genes, Gh_D08G2462, Gh_A03G0043, and Gh_A12G0369, may play important roles in drought tolerance. The current GWAS represents the first investigation into mapping QTL for drought tolerance in G. hirsutum races and provides important information for improving cotton cultivars.

Drought has been identified as a major threat for global crop production worldwide. Phosphofructokinase (PFK) is vital for sugar metabolism. During phosphorylation, plants have two enzymes: ATP-dependent phosphofructokinase (PFK) and pyrophosphate-dependent fructose-6-phosphate phosphotransferase (PFP). Genome-wide identification led to the identification of 80 PFK genes, 26 genes in G. hirsutum and G. barbadense, and 14 genes in G. arboreum and G. raimondii. Phylogenetic, gene structure, and motif analyses showed that PFK genes were grouped into two main categories, namely, PFK and PFP, with 18 and 8 genes in the allotetraploid species and 10 PFK and 4 PFP genes in the diploid species, respectively. Using the RNA-seq expressions of 26 genes from GhPFK, a co-expression network analysis was performed to identify the hub genes. GhPFK04, GhPFK05, GhPFK09, GhPFK11, GhPFK13, GhPFK14, and GhPFK17 in leaves and GhPFK02, GhPFK09, GhPFK11, GhPFK15, GhPFK16, and GhPFK17 in root tissues were found as hub genes. RT-qPCR analysis validated the expressions of identified hub genes. Interestingly, GhPFK11 and GhPFK17 were identified as common hub genes, and these might be the true candidate genes involved in the drought stress tolerance. In the KEGG enrichment analysis, amino acids such as L-valine, L-histidine, L-glutamine, L-serine, L-homoserine, L-methionine, L-cysteine, and gluconic acid were significantly upregulated, whereas sugars, mainly fructose-1-phosphate, D-mannitol, D-sorbitol, dulcitol, and lactose, were significantly downregulated during drought stress. Genome-wide analysis paves the way for a deeper understanding of the PFK genes and establishes the groundwork for future research into PFK’s role in enhancing drought stress tolerance and sugar metabolism in cotton.

Biomonitoring is an effective way to assess the effects of pollutants on marine ecosystems. As an important fishing region in China, the Chinese Bohai Sea has been contaminated with heavy metals, posing great risks to seafood safety and human health. Herein, the spatiotemporal variations in the concentrations of seven heavy metals (As, Cd, Cr, Cu, Ni, Pb, and Zn) in 11 species of mollusks (658 samples) collected from the Chinese Bohai Sea were studied during 2006–2016. The concentrations of Cr, As, Cd, and Pb in approximately 41%, 100%, 71%, and 18% of the sampled mollusks exceeded the maximum permissible levels in aquatic products set by China, indicating that the mollusks were contaminated with varied concentrations of heavy metals. Except for slight fluctuations, no significant temporal variations were observed during the sampling period, suggesting a relatively stable status of these metals. Cluster analysis showed that oyster had higher bioaccumulation potential for Zn and Cu, whereas Mactra veneriformis, Rapana venosa, Meretrix meretrix, Chlamys farreri, and Mya arenaria had higher bioaccumulation potentials for Cr, As, Ni, Cd, and Pb, respectively. These findings are useful for biomonitoring and developing guidelines for seafood consumption in coastal regions. Significant relationships were observed between heavy metal concentrations in mollusks and socioeconomic indices (gross domestic product, per capita gross domestic product, and population amount), suggesting the effects of anthropogenic activities on heavy metal contamination. Our study established a good model to evaluate the risks of heavy metals and provided a sound scientific basis for controlling seafood safety in coastal regions.

The most devastating abiotic factors worldwide are drought and salinity, causing severe bottlenecks in the agricultural sector. To acclimatize to these harsh ecological conditions, plants have developed complex molecular mechanisms involving diverse gene families. Among them, S-adenosyl-L-methionine synthetase (SAMS) genes initiate the physiological, morphological, and molecular changes to enable plants to adapt appropriately. We identified and characterized 16 upland cotton SAMS genes (GhSAMSs). Phylogenetic analysis classified the GhSAMSs into three major groups closely related to their homologs in soybean. Gene expression analysis under drought and salt stress conditions revealed that GhSAMS2, which has shown the highest interaction with GhCBL10 (a key salt responsive gene), was the one that was most induced. GhSAMS2 expression knockdown via virus-induced gene silencing (VGIS) enhanced transgenic plants’ susceptibility to drought and salt stress. The TRV2:GhSAMS2 plants showed defects in terms of growth and physiological performances, including antioxidative processes, chlorophyll synthesis, and membrane permeability. Our findings provide insights into SAMS genes’ structure, classification, and role in abiotic stress response in upland cotton. Moreover, they show the potential of GhSAMS2 for the targeted improvement of cotton plants’ tolerance to multiple abiotic stresses.

The ternary metal sulfide CdIn2S4 (CIS) has great application potential in solar-to-hydrogen conversion due to its suitable band gap, good stability and low cost. However, the photocatalytic hydrogen (H2) evolution performance of CIS is severely limited by the rapid electron–hole recombination originating from the slow photogenerated hole transfer kinetics. Herein, by simply depositing cobalt phosphate (CoHxPOy, noted as Co-Pi), a non-precious co-catalyst, an efficient pathway for accelerating the hole transfer process and subsequently promoting the H2 evolution reaction (HER) activity of CIS nanosheets is developed. X-ray photoelectron spectroscopy (XPS) reveals that the Co atoms of Co-Pi preferentially combine with the unsaturated S atoms of CIS to form Co-S bonds, which act as channels for fast hole extraction from CIS to Co-Pi. Electron paramagnetic resonance (EPR) and time-resolved photoluminescence (TRPL) showed that the introduction of Co-Pi on ultrathin CIS surface not only increases the probability of photogenerated holes arriving the catalyst surface, but also prolongs the charge carrier’s lifetime by reducing the recombination of electrons and holes. Therefore, Co-Pi/CIS exhibits a satisfactory photocatalytic H2 evolution rate of 7.28 mmol g−1 h−1 under visible light, which is superior to the pristine CIS (2.62 mmol g−1 h−1) and Pt modified CIS (3.73 mmol g−1 h−1).

It was shown that microRNAs (miRNAs) play an important role in the synthesis of milk fat; thus, this manuscript evaluated whether exogenous miRNA (xeno-miRNAs) from alfalfa could influence the milk fat content in dairy cows. At first, mtr-miR168b was screened from dairy cow milk and blood. Then, EdU staining, flow cytometry, Oil Red O staining, qRT-PCR, and WB were applied to explore the effect of xeno-miR168b on the proliferation, apoptosis, and lipid metabolism of bovine mammary epithelial cells (BMECs). Finally, in order to clarify the pathway that regulated the lipid metabolism of BMECs using xeno-miR168b, a double-luciferase reporter assay was used to verify the target gene related to milk fat. These results showed that overexpression of xeno-miR168b inhibited cell proliferation but promoted apoptosis, which also decreased the expression of several lipid metabolism genes, including PPARγ, SCD1, C/EBPβ, and SREBP1, significantly inhibited lipid droplet formation, and reduced triglyceride content in BMECs. Furthermore, the targeting relationship between CPT1A and xeno-miR168b was determined and it was confirmed that CPT1A silencing reduced the expression of lipid metabolism genes and inhibited fat accumulation in BMECs. These findings identified xeno-miR168b from alfalfa as a cross-kingdom regulatory element that could influence milk fat content in dairy cows by modulating CPT1A expression.

Abstract Background Segregation distortion (SD) is a common phenomenon among stable or segregating populations, and the principle behind it still puzzles many researchers. The F2:3 progenies developed from the wild cotton species of the D genomes were used to investigate the possible plant transcription factors within the segregation distortion regions (SDRs). A consensus map was developed between two maps from the four D genomes, map A derived from F2:3 progenies of Gossypium klotzschianum and G. davidsonii while Map B from G. thurberi and G. trilobum F2:3 generations. In each map, 188 individual plants were used. Results The consensus linkage map had 1 492 markers across the 13 linkage groups with a map size of 1 467.445 cM and an average marker distance of 1.037 0 cM. Chromosome D502 had the highest percentage of SD with 58.6%, followed by Chromosome D507 with 47.9%. Six thousand and thirty-eight genes were mined within the SDRs on chromosome D502 and D507 of the consensus map. Within chromosome D502 and D507, 2 308 and 3 730 genes were mined, respectively, and were found to belong to 1 117 gourp out of which 622 groups were common across the two chromosomes. Moreover, genes within the top 9 groups related to plant resistance genes (R genes), whereas 188 genes encoding protein kinase domain (PF00069) comprised the largest group. Further analysis of the dominant gene group revealed that 287 miRNAs were found to target various genes, such as the gra-miR398, gra-miR5207, miR164a, miR164b, miR164c among others, which have been found to target top-ranked stress-responsive transcription factors such as NAC genes. Moreover, some of the stress- responsive cis-regulatory elements were also detected. Furthermore, RNA profiling of the genes from the dominant family showed that higher numbers of genes were highly upregulated under salt and osmotic stress conditions, and also they were highly expressed at different stages of fiber development. Conclusion The results indicated the critical role of the SDRs in the evolution of the key regulatory genes in plants.

Abstract Background Wild species of cotton are excellent resistance to abiotic stress. Diploid D-genome cotton showed abundant phenotypic diversity and was the putative donor species of allotetraploid cotton which produce the largest textile natural fiber. Results A total of 41,053 genes were expressed in all samples by mapping RNA-seq Illumina reads of G. thurberi (D1), G. klotzschianum (D3-k), G. raimondii (D5) and G. trilobum (D8) to reference genome. The numbers of differently expressed genes (DEGs) were significantly higher under cold stress than salt stress. However, 34.1% DEGs under salt stress were overlapped with cold stress in four species. Notably, a potential shared network (cold and salt response, including 16 genes) was mined out by gene co-expression analysis. A total of 47,180–55,548 unique genes were identified in four diploid species by De novo assembly. Furthermore, 163, 344, 330, and 161 positively selected genes (PSGs) were detected in thurberi, G. klotzschianum, G. raimondii and G. trilobum by evolutionary analysis, respectively, and 9.5–17% PSGs of four species were DEGs in corresponding species under cold or salt stress. What’s more, most of PSGs were enriched GO term related to response to stimulation. G. klotzschianum showed the best tolerance under both cold and salt stress. Interestingly, we found that a RALF-like protein coding gene not only is PSGs of G. klotzschianum, but also belongs to the potential shared network. Conclusion Our study provided new evidence that gene expression variations of evolution by natural selection were essential drivers of the morphological variations related to environmental adaptation during evolution. Additionally, there exist shared regulated networks under cold and salt stress, such as Ca2+ signal transduction and oxidation-reduction mechanisms. Our work establishes a transcriptomic selection mechanism for altering gene expression of the four diploid D-genome cotton and provides available gene resource underlying multi-abiotic resistant cotton breeding strategy.

Abstract Background For ventral hernia, endoscopic sublay repair (ESR) may overcome the disadvantages of open sublay and laparoscopic intraperitoneal onlay mesh repair. This retrospective study presents the preliminary multicenter results of ESR from China. The feasibility, safety, and effectiveness of ESR were evaluated; its surgical points and indications were summarized. Methods The study reviewed 156 ventral hernia patients planned to perform with ESR in ten hospitals between March 2016 and July 2019. Patient demographics, hernia characteristics, operative variables, and surgical results were recorded and analyzed. Results ESR was performed successfully in 153 patients, 135 with totally extraperitoneal sublay (TES) and 18 with transabdominal sublay (TAS). In 19 patients, TES was performed with the total visceral sac separation (TVS) technique, in which the space separation is carried out along the peritoneum, avoiding damage to the aponeurotic structure. Endoscopic transversus abdominis release (eTAR) was required in 17.0% of patients, and only 18.3% of patients required permanent mesh fixation. The median operative time was 135 min. Most patients had mild pain and resume eating soon after operation. No severe intraoperative complications occurred. Bleeding in the extraperitoneal space occurred in two patients and was stopped by nonsurgical treatment. Seroma and chronic pain were observed in 5.23 and 3.07% of patients. One recurrence occurred after TAS repair for an umbilical hernia. Conclusion ESR is feasible, safe, and effective for treating ventral hernias when surgeons get the relevant surgical skills, such as the technique of “partition breaking,” TVS, and eTAR. Small-to-medium ventral hernias are the major indications.

Abstract Background Cotton is mainly grown for its natural fiber and edible oil. The fiber obtained from cotton is the indispensable raw material for the textile industries. The ever changing climatic condition, threatens cotton production due to a lack of sufficient water for its cultivation. Effects of drought stress are estimated to affect more than 50% of the cotton growing regions. To elucidate the drought tolerance phenomenon in cotton, a backcross population was developed from G. tomentosum, a drought tolerant donor parent and G. hirsutum which is highly susceptible to drought stress. Results A genetic map of 10 888 SNP markers was developed from 200 BC2F2 populations. The map spanned 4 191.3 centi-Morgan (cM), with an average distance of 0.104 7 cM, covering 51% and 49% of At and Dt sub genomes, respectively. Thirty stable Quantitative trait loci (QTLs) were detected, in which more than a half were detected in the At subgenome. Eighty-nine candidate genes were mined within the QTL regions for three traits: cell membrane stability (CMS), saturated leaf weight (SLW) and chlorophyll content. The genes had varied physiochemical properties. A majority of the genes were interrupted by introns, and only 15 genes were intronless, accounting for 17% of the mined genes. The genes were found to be involved molecular function (MF), cellular component (CC) and biological process (BP), which are the main gene ontological (GO) functions. A number of miRNAs were detected, such as miR164, which is associated with NAC and MYB genes, with a profound role in enhancing drought tolerance in plants. Through RT-qPCR analysis, 5 genes were found to be the key genes involved in enhancing drought tolerance in cotton. Wild cotton harbors a number of favorable alleles, which can be exploited to aid in improving the narrow genetic base of the elite cotton cultivars. The detection of 30 stable QTLs and 89 candidate genes found to be contributed by the donor parent, G. tomentosum, showed the significant genes harbored by the wild progenitors which can be exploited in developing more robust cotton genotypes with diverse tolerance levels to various environmental stresses. Conclusion This was the first study involving genome wide association mapping for drought tolerance traits in semi wild cotton genotypes. It offers an opportunity for future exploration of these genes in developing highly tolerant cotton cultivars to boost cotton production.

Abstract Background Cotton grows in altering environments that are often unfavorable or stressful for its growth and development. Consequently, the plant must cope with abiotic stresses such as soil salinity, drought, and excessive temperatures. Alkali-salt stress response remains a cumbersome biological process and is regulated via a multifaceted transcriptional regulatory network in cotton. Results To discover the molecular mechanisms of alkali-salt stress response in cotton, a comprehensive transcriptome analysis was carried out after alkali-salt stress treatment in three accessions of Gossypium hirsutum with contrasting phenotype. Expression level analysis proved that alkali-salt stress response presented significant stage-specific and tissue-specific. GO enrichment analysis typically suggested that signal transduction process involved in salt-alkali stress response at SS3 and SS12 stages in leaf; carbohydrate metabolic process and oxidation-reduction process involved in SS48 stages in leaf; the oxidation-reduction process involved at all three phases in the root. The Co-expression analysis suggested a potential GhSOS3/GhCBL10-SOS2 network was involved in salt-alkali stress response. Furthermore, Salt-alkali sensitivity was increased in GhSOS3 and GhCBL10 Virus-induced Gene Silencing (VIGS) plants. Conclusion The findings may facilitate to elucidate the underlying mechanisms of alkali-salt stress response and provide an available resource to scrutinize the role of candidate genes and signaling pathway governing alkali-salt stress response.

Fibroblast-like synoviocytes (FLSs) play a key role in controlling synovial inflammation and joint destruction in rheumatoid arthritis (RA). The contribution of long noncoding RNAs (lncRNAs) to RA is largely unknown. Here, we show that the lncRNA LINK-A, located mainly in cytoplasm, has higher-than-normal expression in synovial tissues and FLSs from patients with RA. Synovial LINK-A expression was positively correlated with the severity of synovitis in patients with RA. LINK-A knockdown decreased migration, invasion, and expression and secretion of matrix metalloproteinases and proinflammatory cytokines in RA FLSs. Mechanistically, LINK-A controlled RA FLS inflammation and invasion through regulation of tyrosine protein kinase 6–mediated and leucine-rich repeat kinase 2–mediated HIF-1α. On the other hand, we also demonstrate that LINK-A could bind with microRNA 1262 as a sponge to control RA FLS aggression but not inflammation. Our findings suggest that increased level of LINK-A may contribute to FLS-mediated rheumatoid synovial inflammation and aggression. LINK-A might be a potential therapeutic target for RA.

Low temperature is a common biological abiotic stress in major cotton-growing areas. Cold stress significantly affects the growth, yield, and yield quality of cotton. Therefore, it is important to develop more robust and cold stress-resilient cotton germplasms. In response to climate change and erratic weather conditions, plants have evolved various survival mechanisms, one of which involves the induction of various stress responsive transcript factors, of which the C-repeat-binding factors (CBFs) have a positive effect in enhancing plants response to cold stress. In this study, genomewide identification and functional characterization of the cotton CBFs were carried out. A total of 29, 28, 25, 21, 30, 26, and 15 proteins encoded by the CBF genes were identified in seven Gossypium species. A phylogenetic evaluation revealed seven clades, with Clades 1 and 6 being the largest. Moreover, the majority of the proteins encoded by the genes were predicted to be located within the nucleus, while some were distributed in other parts of the cell. Based on the transcriptome and RT-qPCR analysis, Gthu17439 (GthCBF4) was highly upregulated and was further validated through forward genetics. The Gthu17439 (GthCBF4) overexpressed plants exhibited significantly higher tolerance to cold stress, as evidenced by the higher germination rate, increased root growth, and high-induction levels of stress-responsive genes. Furthermore, the overexpressed plants under cold stress had significantly reduced oxidative damage due to a reduction in hydrogen peroxide (H2O2) production. Moreover, the overexpressed plants under cold stress had minimal cell damage compared to the wild types, as evidenced by the Trypan and 3,3′-Diaminobenzidine (DAB) staining effect. The results showed that the Gthu17439 (GthCBF4) could be playing a significant role in enhancing cold stress tolerance in cotton and can be further exploited in developing cotton germplasm with improved cold-stress tolerance.

Drought and low-temperature stresses are the most prominent abiotic stresses affecting cotton. Wild cotton being exposed to harsh environments has more potential to cope with both biotic and abiotic stresses. Exploiting wild cotton material to induce resistant germplasm would be of greater interest. The candidate gene was identified in the BC2F2 population among Gossypium tomentosum and Gossypium hirsutum as wild male donor parent noted for its drought tolerance and the recurrent parent and a high yielding but drought susceptible species by genotyping by sequencing (GBS) mapping. Golden2-like (GLK) gene, which belongs to the GARP family, is a kind of plant-specific transcription factor (TF) that was silenced by virus-induced gene silencing (VIGS). Silencing of GhGLK1 in cotton results in more damage to plants under drought and cold stress as compared with wild type (WT). The overexpression of GhGLK1 in Arabidopsis thaliana showed that the overexpressing plants showed more adaptability than the WT after drought and cold treatments. The results of trypan blue and 3,3′-diaminobenzidine (DAB) staining showed that after drought and cold treatment, the leaf damage in GhGLK1 overexpressed plants was less as compared with the WT, and the ion permeability was also lower. This study suggested that the GhGLK1 gene may be involved in the regulation of drought and cold stress response in cotton. Our current research findings add significantly to the existing knowledge of cold and drought stress tolerance in cotton.

Cotton is one of the most important fiber crops globally. Despite this, various abiotic stresses, including drought, cause yield losses. We used transcriptome profiles to investigate the co-expression patterns of gene networks associated with drought stress tolerance. We identified three gene modules containing 3,567 genes highly associated with drought stress tolerance. Within these modules, we identified 13 hub genes based on intramodular significance, for further validation. The yellow module has five hub genes (Gh_A07G0563, Gh_D05G0221, Gh_A05G3716, Gh_D12G1438, and Gh_D05G0697), the brown module contains three hub genes belonging to the aldehyde dehydrogenase (ALDH) gene family (Gh_A06G1257, Gh_A06G1256, and Gh_D06G1578), and the pink module has five hub genes (Gh_A02G1616, Gh_D12G2599, Gh_D07G2232, Gh_A02G0527, and Gh_D07G0629). Based on RT-qPCR results, the Gh_A06G1257 gene has the highest expression under drought stress in different plant tissues and it might be the true candidate gene linked to drought stress tolerance in cotton. Silencing of Gh_A06G1257 in cotton leaves conferred significant sensitivity in response to drought stress treatments. Overexpression of Gh_A06G1257 in Arabidopsis also confirms its role in drought stress tolerance. L-valine, Glutaric acid, L-proline, L-Glutamic acid, and L-Tryptophan were found to be the most significant metabolites playing roles in drought stress tolerance. These findings add significantly to existing knowledge of drought stress tolerance mechanisms in cotton.

The acyl-coenzyme A oxidase 3 (ACX3) gene involved in the β-oxidation pathway plays a critical role in plant growth and development as well as stress response. Earlier on, studies focused primarily on the role of β-oxidation limited to fatty acid breakdown. However, ACX3 peroxisomal β-oxidation pathways result in a downstream cascade of events that act as a transduction of biochemical and physiological responses to stress. A role that is yet to be studied extensively. In this study, we identified 20, 18, 22, 23, 20, 11, and 9 proteins in Gossypium hirsutum, G. barbadense, G. tomentosum, G. mustelinum, G. darwinii, G. arboretum, and G. raimondii genomes, respectively. The tetraploid cotton genome had protein ranging between 18 and 22, while diploids had between 9 and 11. After analyzing the gene family evolution or selection pressure, we found that this gene family undergoes purely segmental duplication both in diploids and tetraploids. W-Box (WRKY-binding site), ABRE, CAAT–Box, TATA-box, MYB, MBS, LTR, TGACG, and CGTCA-motif are abiotic stress cis-regulatory elements identified in this gene family. All these are the binding sites for abiotic stress transcription factors, indicating that this gene is essential. Genes found in G. hirsutum showed a clear response to drought and salinity stress, with higher expression under drought and salt stress, particularly in the leaf and root, according to expression analysis. We selected Gh_DO1GO186, one of the highly expressed genes, for functional characterization. We functionally characterized the GhACX3 gene through overexpression and virus-induced gene silencing (VIGS). Overexpression of this gene enhanced tolerance under stress, which was exhibited by the germination assay. The overexpressed seed growth rate was faster relative to control under drought and salt stress conditions. The survival rate was also higher in overexpressed plants relative to control plants under stress. In contrast, the silencing of the GhACX3 gene in cotton plants resulted in plants showing the stress susceptibility phenotype and reduced root length compared to control. Biochemical analysis also demonstrated that GhACX3-silenced plants experienced oxidative stress while the overexpressed plants did not. This study has revealed the importance of the ACX3 family during stress tolerance and can breed stress-resilient cultivar.

Background and Aims: Whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident chronic kidney disease (CKD) independent of established cardio-renal risk factors remains controversial. We aimed to provide a quantitative estimate of the association and strength between NAFLD and risk of CKD after adjustment for multiple cardio-renal risk factors. Methods: We searched electronic databases (PubMed, Embase, and Google Scholar) for studies published from database inception until 30 November 2020. Analysis included cohort studies that reported multivariable-adjusted risk ratios [including odds ratios, relative risks (RRs), or hazard ratios] and 95% confidence intervals (CIs) for CKD of NAFLD compared with individuals without NAFLD. Results: A total of 11 cohort studies were included comprising 1,198,242 participants (46.3% women) for analysis. The median follow-up duration was 3.7 years, with 31,922 cases of incident CKD. Compared with individuals without NAFLD, unadjusted models showed that NAFLD was associated with a higher risk of CKD (RR 1.54, 95% CI 1.38–1.71). After adjusting for multiple cardio-renal risk factors, the CKD risk was still significantly increased in patients with NAFLD (RR 1.39, 95% CI 1.27–1.52). Compared with individuals without NAFLD, the adjusted absolute risk increase in NAFLD for CKD was 5.1 (95% CI 3.5–6.8) per 1000 person-years. Conclusion: NAFLD is associated with an increased risk of incident CKD independent of established cardio-renal risk factors.

Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

Abstract Background The efficient detection and initiation of appropriate response to abiotic stresses are important to plants survival. The plant G-protein coupled receptors (GPCRs) are diverse membranous proteins that are responsible for signal transduction. Results In this research work, we identified a novel gene of the GPCR domain, transformed and carried out the functional analysis in Arabidopsis under drought and cold stresses. The transgenic lines exposed to drought and cold stress conditions showed higher germination rate, increased root length and higher fresh biomass accumulation. Besides, the levels of antioxidant enzymes, glutathione (GSH) and ascorbate peroxidase (APX) exhibited continuously increasing trends, with approximately threefold higher than the control, implying that these ROS-scavenging enzymes were responsible for the detoxification of ROS induced by drought and cold stresses. Similarly, the transgenic lines exhibited stable cell membrane stability (CMS), reduced water loss rate in the detached leaves and significant values for the saturated leaves compared to the wild types. Highly stress-responsive miRNAs were found to be targeted by the novel gene and based on GO analysis; the protein encoded by the gene was responsible for maintaining an integral component of membrane. In cotton, the virus-induced gene silencing (VIGS) plants exhibited a higher susceptibility to drought and cold stresses compared to the wild types. Conclusion The novel GPCR gene enhanced drought and cold stress tolerance in transgenic Arabidopsis plants by promoting root growth and induction of ROS scavenging enzymes. The outcome showed that the gene had a role in enhancing drought and cold stress tolerance, and can be further exploited in breeding for more stress-resilient and tolerant crops.

Abstract Background Auxins play an important role in plant growth and development; the auxins responsive gene; auxin/indole-3-acetic acid (Aux/IAA), small auxin-up RNAs (SAUR) and Gretchen Hagen3 (GH3) control their mechanisms. The GH3 genes function in homeostasis by the catalytic activities in auxin conjugation and bounding free indole-3-acetic acid (IAA) to amino acids. Results In our study, we identified the GH3 genes in three cotton species; Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii, analyzed their chromosomal distribution, phylogenetic relationships, cis-regulatory element function and performed virus induced gene silencing of the novel Gh_A08G1120 (GH3.5) gene. The phylogenetic tree showed four clusters of genes with clade 1, 3 and 4 having mainly members of the GH3 of the cotton species while clade 2 was mainly members belonging to Arabidopsis. There were no paralogous genes, and few orthologous genes were observed between Gossypium and other species. All the GO terms were detected, but only 14 genes were found to have described GO terms in upland cotton, more biological functions were detected, as compared to the other functions. The GH3.17 subfamily harbored the highest number of the cis-regulatory elements, most having promoters towards dehydration-responsiveness. The RNA expression analysis revealed that 10 and 8 genes in drought and salinity stress conditions respectively were upregulated in G. hirsutum. All the genes that were upregulated in plants under salt stress conditions were also upregulated in drought stress; moreover, Gh_A08G1120 (GH3.5) exhibited a significant upregulation across the two stress factors. Functional characterization of Gh_A08G1120 (GH3.5) through virus-induced gene silencing (VIGS) revealed that the VIGS plants ability to tolerate drought and salt stresses was significantly reduced compared to the wild types. The chlorophyll content, relative leaf water content (RLWC), and superoxide dismutase (SOD) concentration level were reduced significantly while malondialdehyde concentration and ion leakage as a measure of cell membrane stability (CMS) increased in VIGS plants under drought and salt stress conditions. Conclusion This study revealed the significance of the GH3 genes in enabling the plant’s adaptation to drought and salt stress conditions as evidenced by the VIGS results and RT-qPCR analysis.

Abstract Background Cotton is a leading natural fiber crop. Beyond its fiber, cottonseed is a valuable source of plant protein and oil. Due to the much higher value of cotton fiber, there is less consideration of cottonseed quality despite its potential value. Though some QTL controlling cottonseed quality have been identified, few of them that warrant further study are known. Identifying stable QTL controlling seed size, oil and protein content is necessary for improvement of cottonseed quality. Results In this study, a recombinant inbred line (RIL) population was developed from a cross between upland cotton cultivars/lines Yumian 1 and M11. Specific locus amplified fragment sequencing (SLAF-seq) technology was used to construct a genetic map that covered 3353.15 cM with an average distance between consecutive markers of 0.48 cM. The seed index, together with kernel size, oil and protein content were further used to identify QTL. In total, 58 QTL associated with six traits were detected, including 13 stable QTL detected in all three environments and 11 in two environments. Conclusion A high resolution genetic map including 7033 SNP loci was constructed through specific locus amplified fragment sequencing technology. A total of 13 stable QTL associated with six cottonseed quality traits were detected. These stable QTL have the potential for fine mapping, identifying candidate genes, elaborating molecular mechanisms of cottonseed development, and application in cotton breeding programs.