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Abstract Background Many elite genes have been identified from the available cotton genomic data, providing various genetic resources for gene-driven breeding. However, backbone cultivar-driven breeding is the most widely applied strategy. Revealing the genetic basis of cultivar-driven strategy’s restriction is crucial for transition of cotton breeding strategy. Result CRI12 is a backbone cultivar in cultivar-driven breeding. Here we sequence the pedigree of CRI12 using Nanopore long-read sequencing. We construct a graphical pedigree genome using the high-quality CRI12 genome and 13,138 structural variations within 20 different pedigree members. We find that low hereditary stability of elite segments in backbone cultivars is a drawback of cultivar-driven strategy. We also identify 623 functional segments in CRI12 for multiple agronomic traits in presence and absence variation-based genome-wide association study on three cohorts. We demonstrate that 25 deleterious segments are responsible for the geographical divergence of cotton in pathogen resistance. We also characterize an elite pathogen-resistant gene (GhKHCP) utilized in modern cotton breeding. In addition, we identify 386 pedigree fingerprint segments by comparing the segments of the CRI12 pedigree with those of a large cotton population. Conclusion We characterize the genetic patterns of functional segments in the pedigree of CRI12 using graphical genome method, revealing restrictions of cultivar-driven strategies in cotton breeding. These findings provide theoretical support for transitioning from cultivar-driven to gene-driven strategy in cotton breeding.

Abstract Objective The purpose of this study was to compare the therapeutic effects of Kirschner wire fixation and external fixation in the treatment of proximal humeral fractures in older children and adolescents. Methods A retrospective analysis was performed on the clinical data of older children and adolescents who underwent surgery at our institution for proximal humeral fractures between April 2014 and May 2022. One group (n = 28) underwent fracture reduction and Kirschner wire fixation, and the other group (n = 23) underwent external fixation. During the follow-up, the differences in shoulder joint function between the two groups were compared by analysing Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) and Constant-Murley scores. Postoperative complications were also recorded. Results The operation time of the Kirschner wire group was shorter than that of the external fixation group (69.07 ± 11.34 min vs. 77.39 ± 15.74 min, P = 0.33). The time to remove the fixator in the external fixation group was shorter than that in the Kirschner wire group (6.74 ± 1.57 vs. 7.61 ± 1.22, P = 0.032). The Quick DASH score and Constant-Murley score of the patients in the external fixation group were significantly better than those in the Kirschner wire group at 3 months after surgery (5.63 ± 4.33 vs. 8.93 ± 6.40, P = 0.040; 93.78 ± 2.43 vs. 91.75 ± 2.15, P = 0.003). There was no significant difference in the Quick DASH score or Constant-Murley score between the patients in the external fixator group and those in the Kirschner wire group at 9 months after the operation (2.77 ± 3.14 vs. 3.17 ± 3.68, P = 0.683; 97.39 ± 1.80 vs. 96.57 ± 2.15, P = 0.152). The most common complication of the two groups was pin tract infection. The incidence rate of infection was higher in the external fixation group than that in the Kirschner wire group (9 vs. 4, P = 0.043). Conclusion Both Kirschner wire fixation and external fixation of N-H III and IV proximal humeral fractures in older children and adolescents produce good outcomes. External fixation is a preferred surgical treatment option for paediatric proximal humerus fractures because early mobilization of the affected limb can be realized.

Abstract Background Cotton is the source of natural fibers globally, fulfilling 90% of the textile industry's requirements. However, fiber development is a complex biological process comprising four stages. Fiber develops from a single cell, and cell elongation is a vital process in fiber development. Therefore, it is pertinent to understand and exploit mechanisms underlying cell elongation during fiber development. A previous report about cell division control protein 42 (CDC-42) with its key role in cell elongation in eukaryotes inspired us to explore its homologs Rho GTPases for understanding of cell elongation during cotton fiber development. Result We classified 2 066 Rho proteins from 8 Gossypium species into 5 and 8 groups within A and D sub-genomes, respectively. Asymmetric evolution of Rho members was observed among five tetraploids. Population fixation statistics between two short and long fiber genotypes identified highly diverged regions encompassing 34 Rho genes in G. hirustum, and 31 of them were retained through further validation by genome wide association analysis (GWAS). Moreover, a weighted gene co-expression network characterized genome-wide expression patteren of Rho genes based on previously published transcriptome data. Twenty Rho genes from five modules were identified as hub genes which were potentially related to fiber development. Interaction networks of 5 Rho genes based on transcriptional abundance and gene ontology (GO) enrichment emphasized the involvement of Rho in cell wall biosynthesis, fatty acid elongation, and other biological processes. Conclusion Our study characterized the Rho proteins in cotton, provided insights into the cell elongation of cotton fiber and potential application in cotton fiber improvement.

Abstract Background Upland cotton provides the most natural fiber in the world. During fiber development, the quality and yield of fiber were influenced by gene transcription. Revealing sequence features related to transcription has a profound impact on cotton molecular breeding. We applied convolutional neural networks to predict gene expression status based on the sequences of gene transcription start regions. After that, a gradient-based interpretation and an N-adjusted kernel transformation were implemented to extract sequence features contributing to transcription. Results Our models had approximate 80% accuracies, and the area under the receiver operating characteristic curve reached over 0.85. Gradient-based interpretation revealed 5' untranslated region contributed to gene transcription. Furthermore, 6 DOF binding motifs and 4 transcription activator binding motifs were obtained by N-adjusted kernel-motif transformation from models in three developmental stages. Apart from 10 general motifs, 3 DOF5.1 genes were also detected. In silico analysis about these motifs’ binding proteins implied their potential functions in fiber formation. Besides, we also found some novel motifs in plants as important sequence features for transcription. Conclusions In conclusion, the N-adjusted kernel transformation method could interpret convolutional neural networks and reveal important sequence features related to transcription during fiber development. Potential functions of motifs interpreted from convolutional neural networks could be validated by further wet-lab experiments and applied in cotton molecular breeding.

Abstract Objective To evaluate the efficacy of ultra-early rehabilitation on elbow function after Slongo’s external fixation for supracondylar humeral fractures in older children and adolescents. Methods We retrospectively analyzed clinical data from 49 older children (> 8 years) and adolescents with supracondylar humerus fracture who were treated with Slongo’s external fixation in our hospital from January 2016 to August 2020. Twenty-three patients received ultra-early postoperative rehabilitation (rehabilitation group) and 26 patients were not subjected to postoperative rehabilitation (control group). Time to ROM required for functional activity of daily living(ROM-ADL) in both groups was recorded postoperatively. Patients were followed up at 3 and 6 months after surgery to compare the elbow range of motion (ROM) and carrying angle (CA). Postoperative complications were assessed in both groups. Flynn scores and modified Mayo Elbow Performance Scores were also performed. Results The elbow function at 6 months after surgery was significantly better than that at 3 months in the control group (P = 0.32). Time to ROM-ADL in the rehabilitation group was significantly shorter than that of the control group (P = 0.028). The elbow function, Flynn scores, and modified Mayo scores in the rehabilitation group at 3 and 6 months after surgery were significantly better than that of the control group (P(ROM, 3 months and 6 months) = 0.012 vs 0.039; P(Flynn scores, ROM, 3 months and 6 months) = 0.028 vs 0.005; P(Flynn scores, CA, 3 months and 6 months) = 0.032 vs 0.026; P(Modified Mayo scores, 3 months and 6 months) = 0.039 vs 0.024; respectively). There were no iatrogenic injuries, secondary fracture displacements, myositis ossificans, elbow deformities, or other complications in either group. One case of nail tract infection occurred in the rehabilitation group and was cured. Conclusion Slongo’s external fixation is a safe and effective surgical treatment for supracondylar humeral fractures in children over 8 years old and adolescents. Ultra-early rehabilitation treatment for postoperative children can significantly speed up the recovery after surgery.

Abstract Objective The standard surgical treatment for supracondylar humeral fractures in children is closed reduction and percutaneous pinning. Given the need for greater fixation strength and higher risk of joint stiffness for children older than 8 years, external fixation is often performed for treating supracondylar humeral fractures in older children. The aim of this study was to compare the efficacy of lateral entry pins and Slongo’s external fixation for treating supracondylar humeral fractures in older children. Methods Children older than 8 years who underwent surgery for supracondylar humeral fractures at our hospital for surgery from January 2016 to December 2020 are to be retrospectively assessed. One group (n = 36) underwent internal fixation and percutaneous pinning with three lateral Kirschner wires, and the other group (n = 32) underwent Slongo’s external fixator surgery. The demographic data, operation duration, number of fluoroscopies, and fracture healing time were compared between both groups. The elbow joint function was evaluated 6 months after the surgery on the basis of fracture healing time, lifting angle, elbow joint range of motion (ROM), and Flynn score. The incidence of postoperative complications was also recorded. Results There was no significant difference between the two patient groups in terms of the demographic parameters. Compared to external fixation surgery, Kirschner wire surgery required shorter duration and fewer fluoroscopies (P < 0.05). Nevertheless, the fracture healing time was significantly less (P < 0.05), and the elbow ROM and Flynn scores were higher in the external fixator group compared to the Kirschner wire fixation group (P < 0.05). There was one case of secondary fracture displacement in the Kirschner wire group and one of pin tract infection in the external fixator group. No other iatrogenic injuries or complications were observed. Conclusion Maybe Slongo’s external fixator is a suitable alternative treatment option for supracondylar humeral fractures in children older than 8 years since it can achieve better fixation strength and early restoration of elbow joint movement with a lower risk of joint stiffness.

Abstract Objective The prevalence of atrial fibrillation (AF) in type 2 diabetes mellitus (DM) patients under primary care in Hong Kong was yet to be explored. We aimed to evaluate the prevalence of AF in patients with DM so as to provide evidence-based recommendations to incorporate AF screening as a component in regular diabetic risk and complication assessment. The performance of automated BP machine Microlife WatchBP Office AFIB as a screening tool for the detection of AF was also evaluated. Method This was a cross-sectional study. Patients with type 2 DM who attended the regular diabetic risk and complication assessment in the participating clinics from 24 August 2021 to 27 January 2022 were recruited. Blood pressure measurement by Microlife WatchBP Office AFIB and 12-lead ECGs were performed for AF screening. Results Among 2015 DM patients in primary care, the prevalence of AF was found to be 1.9% (95% confidence interval [CI] 1.3–2.6). The prevalence of AF increased with age, from 0.5% in patients aged

Abstract Background Recent years, a soaring number of marketed Trifolium pratense (red clover) extract products have denoted that a rising number of consumers are turning to natural alternatives to manage postmenopausal symptoms. T. pratense ethanolic extract (TPEE) showed immense potential for their uses in the treatment of menopause complications including osteoporosis and hormone dependent diseases. Early diagnosis of osteoporosis can increase the chance of efficient treatment and reduce fracture risks. Currently, the most common diagnosis of osteoporosis is performed by using dual-energy x-ray absorptiometry (DXA). However, the major limitation of DXA is that it is inaccessible and expensive in rural areas to be used for primary care inspection. Hence, serum biomarkers can serve as a meaningful and accessible data for osteoporosis diagnosis. Methods The present study systematically elucidated the anti-osteoporosis and estrogenic activities of TPEE in ovariectomized (OVX) rats by evaluating the bone microstructure, uterus index, serum and bone biomarkers, and osteoblastic and osteoclastic gene expression. Leverage on a pool of serum biomarkers obtained from this study, recursive feature elimination with a cross-validation method (RFECV) was used to select useful biomarkers for osteoporosis prediction. Then, using the key features extracted, we employed five classification algorithms: extreme gradient boosting (XGBoost), random forest, support vector machine, artificial neural network, and decision tree to predict the bone quality in terms of T-score. Results TPEE treatments down-regulated nuclear factor kappa-B ligand, alkaline phosphatase, and up-regulated estrogen receptor β gene expression. Additionally, reduced serum C-terminal telopeptides of type 1 collagen level and improvement in the estrogen dependent characteristics of the uterus on the lining of the lumen were observed in the TPEE intervention group. Among the tested classifiers, XGBoost stood out as the best performing classification model with the highest F1-score and lowest standard deviation. Conclusions The present study demonstrates that TPEE treatment showed therapeutic benefits in the prevention of osteoporosis at the transcriptional level and maintained the estrogen dependent characteristics of the uterus. Our study revealed that, in the case of limited number of features, RFECV paired with XGBoost model could serve as a powerful tool to readily evaluate and diagnose postmenopausal osteoporosis.

Abstract Background The Rumex acetosa has been used in medicinal treatment, food technology and phytotherapeutics in Eastern Asia and many other countries. However, its effect on cardiovascular system and antiplatelet activity remained to be known. In this study, we examined the antiplatelet activity of R. acetosa in detailed manner to understand underlying mechanism. Methods To study this, whole blood was obtained from male Sprague Dawley (SD) rats and aggregation of washed platelets measured using light transmission aggregometry. Intracellular calcium ion concentration ([Ca2+] i ) was measured using Fura-2/AM while ATP release evaluated by luminometer. Activation of integrin αIIbβ3 analyzed by flow cytometry and clot retraction. Furthermore, we studied the signaling pathways mediated by R. acetosa extract by western blot analysis. Results R. acetosa extract markedly inhibited collagen-induced platelet aggregation and ATP release in a dose-dependent manner. It also suppressed [Ca2+] i mobilization, integrin αIIbβ3 activation and clot retraction. The extract significantly attenuated phosphorylation of the MAPK pathway (i.e., ERK1/2, JNK), MKK4, PI3K/Akt, and Src family kinase. Conclusion Taken together, this data suggests that R. acetosa extract exhibits anti-platelet activity via modulating MAPK, PI3K/Akt pathways, and integrin αIIbβ3-mediated inside-out and outside-in signaling, and it may protect against the development of platelet-related cardiovascular diseases.

Abstract Purpose The current gold standard for the diagnosis of white-coat effect is by the 24-h ambulatory blood pressure monitoring (ABPM) which may not be readily available in every primary care setting. Previous studies had shown that deep breathing, through modulating the baroreceptor reflex sensitivity to vagal stimulation over 30 to 60 s, was useful in detection of the white-coat effect. The aim of our study was to evaluate the diagnostic accuracy of the deep breathing test (DBT) as compared with the gold standard of ABPM in the diagnosis of hypertension with white-coat effect in Chinese patients in primary care. Methods This cross sectional study recruited 178 consecutive, eligible, consented, hypertensive patients receiving treatment at a local public primary care Hypertension Clinic. The diagnostic accuracy of the DBT in all recruited patients, patients not taking beta-adrenergic blockers and patients with different clinic SBP cut-off before the DBT by means of area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive and negative predictive values was evaluated. Results The results for the ROC curves for systolic and diastolic BP changes after the DBT were statistically insignificant. The ROC curve was statistically significant for SBP change in patients not taking beta-adrenergic blockers and with pre-DBT clinic SBP ≥ 165 mmHg (ROC curve area of 0.719, 95% CI 0.53 to 0.91, p = 0.04). The corresponding sensitivity and specificity of the DBT were 40.9 and 90.9% respectively if SBP drop was > 30 mmHg. Conclusion The DBT, even though could not be clinically applied to all patients, was proven to be a potential screening and diagnostic test for white-coat effect in Chinese hypertensive patients with a pre-test SBP of ≥165 mmHg and who were not taking beta-adrenergic blockers. Trial registration This study was approved by Kowloon East Cluster/ Kowloon Central Cluster Research Ethics Committee/Institutional Review Board of Hospital Authority of Hong Kong under the registration KC/KE-16-0084/ER-3.

Abstract Background Brucella causes a chronic and debilitating infection that leads to great economic losses and a public health burden. In this study, we demonstrated the brucellacidal effect of heat shock mediated by the induction of pro-inflammatory cytokines, reactive oxygen species (ROS) accumulation and apoptosis in murine macrophages and in mice. Results RAW264.7 cells were incubated at 43 °C, and BALB/c mice were subjected to whole body hyperthermia. The data showed a reduction in bacterial survival in the mice after daily heat exposure. This was accompanied by increased levels of cytokines TNF, IL-6, IL-1β and IFN-γ in the sera of the mice. Gene expression of NF-κB and inducible nitric oxide production were also induced in the mouse splenic cells. In parallel with the bacterial reduction in the mouse model, an increased bactericidal effect was observed in RAW264.7 cells after exposure to heat stress. In addition, the heat stress increased both the nuclear translocation of NF-κB and the expression of the heat shock proteins HSP70 and HSP90 in murine macrophages. Furthermore, heat exposure induced the increase of pro-inflammatory cytokines, ROS accumulation and apoptosis but did not affect the production of nitric oxide (NO) in macrophages. Conclusion This study demonstrated the induction of innate immune responses by heat stress that significantly reduced the intracellular survival of B. abortus in vitro and in vivo. Transcriptional factor NF-κB, which is a master regulator, could be termed a key activator of heat-induced immunity against Brucella. The increase in the expression and activation of NF-κB in splenic cells and macrophages was followed by enhanced antimicrobial effectors, including cytokines, ROS and NO that may contribute to the reduction of bacterial survival.

Abstract Ginsenosides from Panax ginseng are well known for their diverse pharmacological effects including antithrombotic activity. Since adventitious roots of mountain ginseng (ARMG) also contain various ginsenosides, blood flow-improving effects of the dried powder and extract of ARMG were investigated. Rats were orally administered with dried powder (PARMG) or ethanol extract (EARMG) of ARMG (125, 250 or 500 mg/kg) or aspirin (30 mg/kg, a reference control) for 3 weeks. Forty min after the final administration, carotid arterial thrombosis was induced by applying a 70% FeCl3-soaked filter paper outside the arterial wall for 5 min, and the blood flow was monitored with a laser Doppler probe. Both PARMG and EARMG delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at high doses. In mechanism studies, a high concentration of EARMG inhibited platelet aggregation induced by collagen in vitro. In addition, EARMG improved the blood lipid profiles, decreasing triglyceride and cholesterol levels. Although additional action mechanisms remain to be clarified, it is suggested that ARMG containing high amount of ginsenosides such as Rg3 improves blood flow not only by inhibiting oxidative thrombosis, but also by modifying blood lipid profiles.

In this article, So-Young Park is inadvertently omitted from the listed author names. In the Acknowledgement section, funding source is incorrectly cited and has been changed upon request of authors.

Abstract Background Short (~5 nucleotides) interspersed repeats regulate several aspects of post-transcriptional gene expression. Previously we developed an algorithm (REPFIND) that assigns P-values to all repeated motifs in a given nucleic acid sequence and reliably identifies clusters of short CAC-containing motifs required for mRNA localization in Xenopus oocytes. Description In order to facilitate the identification of genes possessing clusters of repeats that regulate post-transcriptional aspects of gene expression in mammalian genes, we used REPFIND to create a database of all repeated motifs in the 3' untranslated regions (UTR) of genes from the Mammalian Gene Collection (MGC). The MGC database includes seven vertebrate species: human, cow, rat, mouse and three non-mammalian vertebrate species. A web-based application was developed to search this database of repeated motifs to generate species-specific lists of genes containing specific classes of repeats in their 3'-UTRs. This computational tool is called 3'-UTR SIRF (Short Interspersed Repeat Finder), and it reveals that hundreds of human genes contain an abundance of short CAC-rich and CAG-rich repeats in their 3'-UTRs that are similar to those found in mRNAs localized to the neurites of neurons. We tested four candidate mRNAs for localization in rat hippocampal neurons by in situ hybridization. Our results show that two candidate CAC-rich (Syntaxin 1B and Tubulin β4) and two candidate CAG-rich (Sec61α and Syntaxin 1A) mRNAs are localized to distal neurites, whereas two control mRNAs lacking repeated motifs in their 3'-UTR remain primarily in the cell body. Conclusion Computational data generated with 3'-UTR SIRF indicate that hundreds of mammalian genes have an abundance of short CA-containing motifs that may direct mRNA localization in neurons. In situ hybridization shows that four candidate mRNAs are localized to distal neurites of cultured hippocampal neurons. These data suggest that short CA-containing motifs may be part of a widely utilized genetic code that regulates mRNA localization in vertebrate cells. The use of 3'-UTR SIRF to search for new classes of motifs that regulate other aspects of gene expression should yield important information in future studies addressing cis-regulatory information located in 3'-UTRs.