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Background: Catheter ablation is a first-line treatment for symptomatic, recurrent supraventricular tachycardia (SVT). This study aims to demonstrate if 3D-electroanatomic mapping (EAM) during SVT ablation reduces fluoroscopy time (FT) and determine if further reductions in FT are observed longitudinally. Methods: All cases of SVT ablation between May 2011–May 2022 at a single tertiary centre were prospectively recruited. FT between the cohorts with and without EAM were compared. Within the EAM subset, the trend of FT across the years was analysed. Results: There were 1758 cases included, 563 without EAM, 1195 with EAM. EAM was associated with a longer procedure time (mean + 8.8 min, p = 0.001), but with mean reductions in FT and dose area product (DAP) by 19.6 min and 18 621 mGy*cm2 respectively (p

Chest pain is a common presenting complaint among patients visiting primary care1 and is a frequent reason for referral to the outpatient cardiology clinic. The European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines advocate estimating pre-test probability (PTP) of obstructive coronary artery disease (CAD) in the evaluation of stable chest pain in order to guide the need for and type of downstream investigations.2,3 The PTP of obstructive CAD depends on the clinical characteristics of the patient and disease prevalence. Since the introduction of the Diamond-Forrester model in 1979,4 contemporary risk scores, such as the CAD consortium score5 (CCS) and the ESC 2019 PTP risk score,2 have been developed.

Abstract Background Facial fractures are common injuries causing cosmetic, functional, and psychological damage. The purpose of this study was to assess the incidence, prevalence, and years lived with disability (YLDs) of facial fractures from 1990 to 2019 using the Global Burden of Disease (GBD). Methods Detailed data for the disease burden of facial fractures were obtained from online available public data (Global Health Data Exchange) derived from the GBD study. The incidence, prevalence, and YLDs of facial fractures from 1990 to 2019 were analyzed by country, region, age, gender, sociodemographic index (SDI), and cause. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized YLDs rate (ASYR), and estimated annual percentage change (EAPC) were calculated to evaluate the disease burden and quantify the trends over time. The main causes of facial fractures in different years and ages were assessed. Results Globally, there were 8.9 million incident cases, 1.5 million cases prevalent cases, and 98.1 thousand years YLDs in 2019. Compared with 1990, the number of incident cases, prevalent cases, and YLDs increased, while ASIR (EAPC, − 0.47; 95% uncertainty interval [UI], − 0.57 to − 0.37), ASPR (EAPC, − 0.39; 95% UI, − 0.46 to − 0.31), ASYR (EAPC, − 0.39; 95% UI, − 0.47 to − 0.32) showed a downward trend. The high SDI region held the highest ASIR, ASPR, and ASYR both in 1990 and 2019, such as New Zealand, Slovenia, and Australia. The burden was higher in men than in women from 1990 to 2019, while the ASRs in women exceeded that of men in the elderly. The ASIR peaked in the young adult group, however, the ASPR and ASYR increased with age. Falls and road injuries were the leading causes of facial fractures. Conclusions Facial fractures continue to cause a heavy burden on public health worldwide. More targeted strategies need to be established to control the burden of facial fractures.

Abstract Acne vulgaris is a type of chronic skin disorder caused by Propionibacterium acnes (P. acnes). Neutrophil extrinsic traps (NETs) play key role in many types of inflammatory skin diseases. Adipose-derived stem cells (ADSCs) was reported modulate immune responses and neutrophil activity. Here, we explored the potential role of ADSCs and the potential mechanism associated with neutrophil extracellular traps (NETs) in relieving acne vulgaris. In the P. acnes-infected ear skin model, histological staining was used to evaluate the inflammatory infiltration and NET formation in control, P. acnes, and P. acnes + ADSCs groups. Besides, western blot was used to detect the expression levels of cit-H3, MPO, and Nrf2 in ear tissue. In vitro, the immunofluorescence staining of MPO and cit-H3, and SYTOX green staining were performed to measure the NET formation. CCK-8 assay, EdU staining, and wound healing assay were used to detect the proliferation and migration abilities of keratinocytes. ELISA assay was utilized to detect the secretion of inflammatory cytokines. In P. acnes-infected ear skin, ADSC treatment significantly attenuated inflammation and NET formation via activating Nrf2 signaling pathway. In vitro, the conditioned medium of ADSCs reduced the formation of P. acne-induced NETs. Besides, ADSCs could inhibit that the NETs efficiently promoted the proliferation, migration, and inflammatory cytokine secretion of keratinocytes. Our study suggested that ADSCs could attenuate P. acne-related inflammation by inhibiting NET formation. This study provides a novel therapeutic perspective of ADSCs in combating acne vulgaris.

Abstract Background and Aim The availability of direct‐acting antiviral (DAA) treatment and point‐of‐care diagnostic testing has made hepatitis C (HCV) elimination possible even in low‐ and middle‐income countries (LMICs); however, testing and treatment costs remain a barrier. We estimated the cost and cost‐effectiveness of a decentralized community‐based HCV testing and treatment program (CT2) in Myanmar. Methods Primary cost data included the costs of DAAs, investigations, medical supplies and other consumables, staff salaries, equipment, and overheads. A deterministic cohort‐based Markov model was used to estimate the average cost of care, the overall quality‐adjusted life years (QALYs) gained, and the incremental cost‐effectiveness ratio (ICER) of providing testing and DAA treatment compared with a modeled counterfactual scenario of no testing and no treatment. Results From 30 January to 30 September 2019, 633 patients were enrolled, of whom 535 were HCV RNA‐positive, 489 were treatment eligible, and 488 were treated. Lifetime discounted costs and QALYs of the cohort in the counterfactual no testing and no treatment scenario were estimated to be USD61790 (57 898–66 898) and 6309 (5682–6363) respectively, compared with USD123 248 (122 432–124 101) and 6518 (5894–6671) with the CT2 model of care, giving an ICER of USD294 (192–340) per QALY gained. This “one‐stop‐shop” model of care has a 90% likelihood of being cost‐effective if benchmarked against a willingness to pay of US$300, which is 20% of Myanmar's GDP per capita (2020). Conclusions The CT2 model of HCV care is cost‐effective in Myanmar and should be expanded to meet the National Hepatitis Control Program's 2030 target, alongside increasing the affordability and accessibility of services.

Abstract Viruses are ubiquitous in the oceans, exhibiting high abundance and diversity. Here, we systematically analyze existing genomic sequences of marine prokaryotes to compile a Marine Prokaryotic Genome Dataset (MPGD, consisting of over 12,000 bacterial and archaeal genomes) and a Marine Temperate Viral Genome Dataset (MTVGD). At least 40% of the MPGD genomes contain one or more proviral sequences, indicating that they are lysogens. The MTVGD includes over 12,900 viral contigs or putative proviruses, clustered into 10,897 viral genera. We show that lysogens and proviruses are abundant in marine ecosystems, particularly in the deep sea, and marine lysogens differ from non-lysogens in multiple genomic features and growth properties. We reveal several virus-host interaction networks of potential ecological relevance, and identify proviruses that appear to be able to infect (or to be transferred between) different bacterial classes and phyla. Auxiliary metabolic genes in the MTVGD are enriched in functions related to carbohydrate metabolism. Finally, we experimentally demonstrate the impact of a prophage on the transcriptome of a representative marine Shewanella bacterium. Our work contributes to a better understanding of the ecology of marine prokaryotes and their viruses.

Abstract Wound healing is a complex physiological process for maintaining skin integrity after a wound. Bone marrow-derived mesenchymal stem cells (BMSCs) are excellent cellular candidates for wound healing, which could be enhanced by exogenous stimulation. We aimed to explore the role of δ-Tocotrienol (δ-TT) in BMSC ability of wound healing. Firstly, transcriptome and single-cell analysis were used to explore the genes and pathways related to ferroptosis in wound tissues. In vitro, cell proliferation, migration, and angiogenesis of δ-TT-BMSCs were detected. In addition, qRT-PCR and immunofluorescence (IF) were applied for observing the promoting wound healing ability of δ-TT-BMSC conditioned medium (CM) on NIH-3T3 and PAM-212 cells. The level of ferroptosis was determined by the mitochondrial membrane potential and total/lipid reactive oxygen species (ROS) in the cells and the morphological changes of mitochondria were observed by transmission electron microscope. The BTB and CNC homology 1 (BACH1) expression and activation of the PI3K/AKT signaling pathway were detected by IF and western blot (WB). The effect of δ-TT-BMSCs on wound healing was observed in vivo. The regulatory mechanism of δ-TT-BMSCs on ferroptosis was verified by IHC and IF staining. In vitro, δ-TT-BMSCs declined the level of lipid ROS in NIH-3T3 and PAM-212 cells and enhanced mitochondrial membrane potential. In vivo, δ-TT-BMSCs promoted wound healing in mice by decreasing ferroptosis. In terms of mechanism, δ-TT-BMSCs inhibited the expression of BACH1 and activated PI3K/AKT signaling pathway. This study demonstrated the ability of δ-TT-BMSCs to promote wound healing by inhibiting BACH1-related ferroptosis. In addition, PI3K/AKT signaling pathway was activated by δ-TT-BMSCs and could be involved in wound healing. δ-TT-BMSCs might be a promising strategy for treating wounds.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) has been well defined as a common chronic liver metabolism disorder. Statins as a first-line therapeutic treatment had some side effects. Here, we found that Fumigaclavine C (FC) was collected from endophytic Aspergillus terreus via the root of Rhizophora stylosa (Rhizophoraceae), had potential anti-adipogenic and hepatoprotective effects both in vitro and in vivo without obvious adverse side effects. However, the mechanisms of the prevention and management of FC for hepatic steatosis are incompletely delineated. Methods The pharmacodynamic effects of FC were measured in high-fat diet (HFD)-induced obese mice. Liver index and blood biochemical were examined. Histopathological examination in the liver was performed by hematoxylin & eosin or oil red O. The levels of serum TG, TC, LDL-c, HDL-c, FFA, T-bili, ALT, AST, creatinine, and creatine kinase were estimated via diagnostic assay kits. The levels of hepatic lipid metabolism-related genes were detected via qRT-PCR. The expression levels of hepatic de novo lipogenesis were quantitated with Western blot analysis. Results FC-treatment markedly reduced hepatic lipid accumulation in HFD-induced obese mice. FC significantly attenuated the hepatic lipid metabolism and ameliorated liver injury without obvious adverse side effects. Moreover, FC also could dose-dependently modulate the expressions of lipid metabolism-related transcription genes. Mechanically, FC notably suppressed sterol response element binding protein-1c mediated de novo lipogenesis via interfering with the RhoA/ROCK signaling pathway by decreasing the levels of geranylgeranyl diphosphate and farnesyl diphosphate. Conclusions These findings suggested that FC could improve hepatic steatosis through inhibiting de novo lipogenesis via modulating the RhoA/ROCK signaling pathway.

The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation, molting, and metamorphosis. Despite its significance, there is a dearth of research on its metabolic impact on the gills and epidermis—key organs in osmoregulation and molting processes. This study employed CHH dsRNA injections to silence CHH gene expression in Procambarus clarkii, followed by a metabolomic analysis of the gills and epidermis using nuclear magnetic resonance spectroscopy. Metabolic profiling through principal component analysis revealed the most pronounced changes at 24 h post-injection (hpi) in the epidermis and at 48 hpi in the gills. At 24 hpi, the epidermis exhibited significant modulation in 25 enrichment sets and 20 KEGG pathways, while at 48 hpi, 5 metabolite sets and 6 KEGG pathways were prominently regulated. Notably, pathways associated with amino acid metabolism, carbohydrate metabolism, and cofactor and vitamin metabolism were affected. A marked decrease in glucose and other carbohydrates suggested a compromised carbohydrate supply, whereas increased levels of citrate cycle intermediates implied a potential boost in energy provision. The silencing of CHH gene expression hampered the carbohydrate supply, which was possibly the main energy derived substrates. Conversely, the gills displayed significant alterations in 15 metabolite sets and 16 KEGG pathways at 48 hpi, with no significant changes at 24 hpi. These changes encompassed amino acid, carbohydrate, and lipid metabolism pathways. The decline in TCA cycle intermediates pointed to a potential downregulation of the cycle, whereas a decrease in ketone bodies indicated a shift towards lipid metabolism for energy production. Additionally, increased levels of nicotinate, nicotinamide, and quinolinate were observed in both organs. Overall, CHH’s impact on the epidermis was prominent at 24 hpi and diminished thereafter, whereas its influence on metabolism in gills was delayed but intensified at 48 hpi. This differential CHH effect between gills and epidermis in P. clarkii provides new insights into the organ-specific regulatory mechanisms of CHH on energy metabolism and osmoregulation, warranting further comparative studies to elucidate the distinct roles of CHH in these organs.

Astaxanthin (AST) is a feed additive applied in aquaculture, which has been proved to promote the growth performance, antioxidant capacity and immunity of crayfish (Procambarus clarkii), an important economic fishery species in China. However, the underlying mechanism of improved antioxidant capacity of AST in crayfish remains unknown. In this study, changes of antioxidant activity, transcriptome and metabolome in crayfish hepatopancreas were analyzed after feeding with AST. The results showed that AST could improve the antioxidant capacity of crayfish via increasing antioxidant enzymes activity and reducing malondialdehyde content. Transcriptomic analysis revealed that immune system, cell death and disease, mitochondrial respiration and oxidative phosphorylation pathways were altered with AST feeding. AST significantly increased total cholesterol level indicated the metabolism of crayfish was affected. Metabolomic analysis revealed the alteration of mineral adsorption, carbon and amino acid metabolisms, and fatty acid biosynthesis. Conjoint analysis of transcriptome and metabolome suggested that AST predominantly regulated amino acid and fatty acid metabolisms. Taken together, AST acts on crayfish mainly through improving antioxidant capacity and modulating amino acid and fatty acid metabolisms.

The segmentation of knee joint is of great significance for diagnosis, guidance and treatment of knee osteoarthritis. However, manual delineation is time-consuming and labor-intensive since various anatomical structures are involved in the 3D MRI volume. Automatic segmentation of the whole knee joint requires no human effort, additionally can improve the quality of arthritis diagnosis and treatment by describing the details more accurately. Existing knee joint segmentation methods in the literature focus on only one or few structures out of many. In this paper, we study the feasibility of knee joint segmentation on MR images based on neural networks and deal with the following challenges: (1) end-to-end segmentation of 15 anatomical structures, including bone and soft tissue, of the whole knee on MR images; (2) robust segmentation of small structures such as the anterior cruciate ligament, accounting for about 0.036% of the volume data. Experiments on the knee joint MR images demonstrate that the average segmentation accuracy of our method achieves 92.92%. The Dice similarity coefficients of 9 structures were above 94%, five structures were between 87% and 90%, and the remaining one was about 76%.

The seven-character short poem [duan ge 短歌] is a distinct poetic form that originated in Han dynasty ballads and peaked during the Liang dynasty. It is closely related to the gexing 歌行 [song or song poem], a poetic form that also flourished during the Qi and Liang dynasties. The two forms differ in substance, with the former tending towards brevity and, the latter, length; however, they share fundamental principles of compositional method. At the start of the Tang dynasty, the seven-character short poem had not yet been eclipsed by the seven-character quatrain [jueju 絕句]; rather, it maintained its place among Early and High Tang poetic forms and continued to develop on its own terms. The “Ten Songs on Kayō [Kayō jūei 河陽十詠]” is a seven-character short poem sequence from the Heian period in Japan. Its formal elements are similar to those of the Chinese seven-character short poem, and it shares structural qualities with Qi-Liang style gexing composed by Heian poets. At the same, it also shares characteristics of the Heian topic poem. Its unique existence prompts us to look back to old poetic forms as precious source materials from which we may excavate long-overlooked stylistic phenomenon in poetry.

Abstract Fat transplantation is widely used for soft‐tissue filling and wound repair. Owing to the biological changes in adipocytes in some metabolic diseases, allograft fat can provide a better source of donor fat than autologous fat. Fingolimod (FTY720) possesses a powerful immunomodulatory function. This study aimed to investigate the protective effect of FTY720 in allogeneic fat transplantation. C57BL/6J mice that received allografts were randomly divided into two groups and treated with saline and FTY720, respectively. Fat graft samples were obtained at 1, 6, and 20 weeks posttransplantation. Graft volumes, graft structure, and immune cells were estimated using histological examination, immunohistochemistry, staining immunofluorescence (IF), and quantitative real‐time polymerase chain reaction (qRT‐PCR). Inflammatory cytokine mRNA expression in grafts was detected by qRT‐PCR. FTY720 treatment significantly enhanced allograft retention, structural integrity, and neovascularization, thereby demonstrating the potential of FTY720 in improving graft survival. Further IF staining showed that FTY720 increased regulatory T cell infiltration and reduced macrophage infiltration to some extent. FTY720 treatment also enhanced the expression of the anti‐inflammatory cytokines interleukin (IL)‐4 and IL‐10 and weakened the expression of the pro‐inflammatory cytokines TNF‐α and IL‐6. Furthermore, FTY720 treatment upregulated the expression of CD31 positive cells. This study demonstrated the potential efficacy of FTY720 in improving the graft survival rate of syngeneic fat allograft models, possibly by suppressing immune rejection and promoting angiogenesis. Therefore, this study offers key insights into the potential application of a drug‐assisted strategy to prolong allograft fat survival.

Hypocalcemic cardiomyopathy is a rare etiology of heart failure. It is considered highly reversible with a relatively favorable prognosis. This case reports a 52-year-old housewife diagnosed with hypocalcemic cardiomyopathy who presented with acute decompensated heart failure and hypocalcemia symptoms with a history of thyroidectomy. Shortness of breath and edema were relieved after diuresis and prompt electrolyte correction. The left ventricular ejection fraction increased from 27% to 53%, and the left ventricular end-diastolic dimension shortened from 58 to 50 mm in echocardiographic re-examinations, while repeat cardiac magnetic resonance imaging revealed evidence of non-reversible cardiac fibrosis after 1-year follow-up. Cardioprotective agents with close follow-ups were called for in this entity of patients.

Ligusticum chuanxiong is a common traditional edible-medicinal herb that has various pharmacological activities. However, its effects on Saccharomyces cerevisiae (S. cerevisiae) remains unknown. In this study, we found that water extract of Ligusticum chuanxiong (abbreviated as WEL) exhibited excellent free radical scavenging ability in-vitro. Moreover, WEL treatment could delay the aging of S. cerevisiae, an important food microorganism sensitive to reactive oxygen species (ROS) stress. Biochemical analyses revealed that WEL significantly increased the activity of antioxidant enzymes in S. cerevisiae, including superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR), as well as their gene expression. As a result, ROS level was significantly decreased and accompanied with the decline of malondialdehyde (MDA), which represented a state of low oxidative stress. The reduction of oxidative stress could elevate S. cerevisiae's ethanol fermentation efficiency. Taken together, WEL plays a protective role against S. cerevisiae aging via improving antioxidant activity.

Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated in vitro against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts a1–a20 exhibited excellent cytotoxic activity. Among them, a6 was the most potent cytotoxic compound with IC50 values of 0.04–0.29 μM. Podophyllotoxin-1,2,3-triazole derivatives b1–b5 displayed medium cytotoxic activity, and podophyllotoxin-amine compounds c1–c3 has good cytotoxic activity with IC50 value of 0.04–0.58 μM. Furthermore, cell cycle and apoptosis experiments of compound a6 were carried out and the results exhibited that a6 could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.

Abstract Background Nowadays, wound is associated with a complicated repairing process and still represents a significant biomedical burden worldwide. Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and secretory function, emerging as potential cellular candidates in treating wounds. Ascorbic acid 2-glucoside (AA2G) is a well-known antioxidant and its function in BMSC-promoting wound healing is worth exploring. Methods The in vitro cell proliferation, migration, and angiogenesis of BMSCs and AA2G-treated BMSCs were detected by flow cytometry, EDU staining, scratch assay, transwell assay, and immunofluorescence (IF). Besides, the collagen formation effect of AA2G-treated BMSCs conditioned medium (CM) on NIH-3T3 cells was evaluated by hydroxyproline, qRT-PCR and IF staining detection. Next, in the wound healing mouse model, the histological evaluation of wound tissue in PBS, BMSCs, and AA2G-treated BMSCs group were further investigated. Lastly, western blot and ELISA were used to detect the expression levels of 5-hmc, TET2 and VEGF protein, and PI3K/AKT pathway activation in BMSCs treated with or without AA2G. Results The in vitro results indicated that AA2G-treated BMSCs exhibited stronger proliferation and improved the angiogenesis ability of vascular endothelial cells. In addition, the AA2G-treated BMSCs CM enhanced migration and collagen formation of NIH-3T3 cells. In vivo, the AA2G-treated BMSCs group had a faster wound healing rate and a higher degree of vascularization in the new wound, compared with the PBS and BMSCs group. Moreover, AA2G preconditioning might enhance the demethylation process of BMSCs by regulating TET2 and up-regulating VEGF expression by activating the PI3K/AKT pathway. Conclusions AA2G-treated BMSCs promoted wound healing by promoting angiogenesis and collagen deposition, thereby providing a feasible strategy to reinforce the biofunctionability of BMSCs in treating wounds.

ObjectiveTo determine whether kidney transplants performed during weekends have worse outcomes than those performed during weekdays.MethodsFor this systematic review, PubMed, EMBASE, and the Cochrane Library (January 2000 to January 2023) were searched. We examined the survival rates of patients and grafts for hospital inpatients admitted during weekends and those admitted during weekdays. To be included, the study had to be in English and had to provide discrete survival data around weekends versus weekdays, including patients who were admitted as inpatients over the weekend.ResultsFive studies (n = 163,506 patients) were examined. The hazards ratio (HR) of the survival rate of patients with weekend transplantation was 1.01 (95% confidence interval [CI], 0.96 to 1.06) when compared with patients with weekday transplantation. Patients who had renal transplant on weekends had an overall allograft survival HR of 1.01 (95% CI, 0.99 to 1.03) and death-censored allograft survival HR of 1.01 (95% CI, 0.98 to 1.04). Comparison of length of hospital stay, rejection, surgical complications, and vascular complications between renal transplants on weekends and those on weekdays showed no statistical difference.ConclusionHospital inpatients admitted for renal transplantation during weekends have a survival rate similar to that of inpatients admitted during weekdays. The weekend effect of renal transplantation was very weak; hence, transplantations done during weekends and weekdays are both appropriate.

Hepatitis C (HCV) infection elimination in low- and middle-income countries requires decentralised HCV services to increase testing and linkage to care. The CT2 Study investigated patients' views of access to and acceptance of two community-based HCV care models in Myanmar using a mixed-methods approach. Point-of-care HCV testing and general practitioner-initiated HCV treatment were provided at two community clinics in Yangon, Myanmar-the Burnet Institute's (BI) clinic focused on people who inject drugs (PWID), and the Myanmar Liver Foundation's (MLF) clinic focused on people with liver-related diseases. Study staff administered quantitative questionnaires to 633 participants receiving anti-HCV antibody testing. Purposive sampling was used to recruit 29 participants receiving direct-acting antiviral treatment for qualitative interviews. Among participants completing quantitative questionnaires, almost all reported the clinic location was convenient (447/463, 97%), waiting time was acceptable (455/463, 98%), and HCV antibody and RNA testing methods were acceptable (617/632, 98% and 592/605, 97% respectively). Nearly all participants were satisfied with their clinic's services (444/463, 96%) and preferred same-day test results (589/632, 93%). BI clinic participants were more confident that they understood HCV antibody and RNA results; MLF clinic participants were more comfortable disclosing their risk behaviour to staff and had slightly higher satisfaction with the overall care, privacy and secure storage of their information. In qualitative interviews, participants reported that flexible appointment scheduling, short wait times and rapid return of results increased the clinic's accessibility. The simplified point-of-care testing and treatment procedures and supportive healthcare providers contributed to participants' acceptance of the HCV care model. This decentralised community-based HCV testing and treatment model was highly accessible and acceptable to CT2 participants. Prioritizing patient-centred care, rapid provision of results, flexible appointments and convenient clinic locations can promote accessible and acceptable services which may in turn help accelerate progress in reaching HCV elimination targets.

With the rapid innovation of nanoscience and technology, nanomaterials have also been deeply applied in the medical and health industry and become one of the innovative methods to treat many diseases. In recent years, bioactive nanomaterials have attracted extensive attention and have made some progress in the treatment of some major chronic diseases, such as nervous system diseases and various malignant tumors. Bioactive nanomaterials depend on their physical and chemical properties (crystal structure, surface charge, surface functional groups, morphology, and size, etc.) and direct produce biological activity and play to the role of the treatment of diseases, compared with the traditional nanometer pharmaceutical preparations, biological active nano materials don’t exert effects through drug release, way more directly, also is expected to be more effective for the treatment of diseases. However, further studies are needed in the evaluation of biological effects, fate in vivo, structure-activity relationship and clinical transformation of bionanomaterials. Based on the latest research reports, this paper reviews the application of bioactive nanomaterials in the diagnosis and treatment of major chronic diseases and analyzes the technical challenges and key scientific issues faced by bioactive nanomaterials in the diagnosis and treatment of diseases, to provide suggestions for the future development of this field.

Abstract Background Recent studies have revealed that circular RNA participates in endometrial carcinoma (EC) progression. Here we investigated the role of circRNA zinc finger protein 124 (circZNF124) in EC genesis and underlying mechanism. Methods The expression levels of circZNF124, microRNA‐199b‐5p (miR‐199b‐5p) and solute carrier family 7 member 5 (SLC7A5) were detected by quantitative real‐time polymerase chain reaction. The expression of SLC7A5 and other indicated marker proteins was determined by western blot analysis. For functional assay, cell proliferation, leucine uptake and metastasis were investigated by total cell number, cell counting kit‐8, cell colony formation, leucine uptake or transwell assay. The interaction between miR‐199b‐5p and circZNF124 or SLC7A5 was predicted by starbase online database, and identified by mechanism assays. The impact of circZNF124 absence on tumor growth in vivo was revealed by xenograft mouse model assay. Immunohistochemistry assay was implemented to detect the positive expression rate of nuclear proliferation marker (Ki67). Results CircZNF124 and SLC7A5 expression were significantly increased, while miR‐199b‐5p was decreased in EC tissues and cells compared with normal endometrial tissues or cells. CircZNF124 expression was closely associated with EC severity and lymph node metastasis. Additionally, circZNF124 depletion repressed cell proliferation, leucine uptake, migration and invasion in both HEC1A and Ishikawa cells. CircZNF124 regulated SLC7A5 expression by binding to miR‐199b‐5p. MiR‐199b‐5p inhibitors or SLC7A5 overexpression attenuated circZNF124 silencing‐mediated EC malignant progression. Furthermore, SLC7A5 absence inhibited tumor growth in vivo. Conclusion CircZNF124 depletion inhibited EC cell malignancy by miR‐199b‐5p/SLC7A5 pathway, which demonstrated that circZNF124 had the potential as a therapeutic target for EC.

Phosphorothioate (PT) modification by the dnd gene cluster is the first identified DNA backbone modification and has been shown to constitute a multifunctional epigenetic system. Despite a variety of advantages for hosting dnd systems, these systems are surprisingly distributed sporadically among contemporary microbial genomes. To address this ecological paradox, Jian et al. systematically investigated the occurrence and phylogeny of dnd systems in prokaryotes, and provided evidence to suggest that dnd systems have originated in ancient Cyanobacteria (probably Nostocales) after the Great Oxygenation Event.

Abstract We investigated whether standardized neuropsychological tests and experimental cognitive paradigms measure the same cognitive faculties. Specifically, do neuropsychological tests commonly used to assess attention measure the same construct as attention paradigms used in cognitive psychology and neuroscience? We built on the “general attention factor”, comprising several widely used experimental paradigms (Huang et al., 2012). Participants (n = 636) completed an on-line battery (TestMyBrain.org) of six experimental tests [Multiple Object Tracking, Flanker Interference, Visual Working Memory, Approximate Number Sense, Spatial Configuration Visual Search, and Gradual Onset Continuous Performance Task (Grad CPT)] and eight neuropsychological tests [Trail Making Test versions A & B (TMT-A, TMT-B), Digit Symbol Coding, Forward and Backward Digit Span, Letter Cancellation, Spatial Span, and Arithmetic]. Exploratory factor analysis in a subset of 357 participants identified a five-factor structure: (1) attentional capacity (Multiple Object Tracking, Visual Working Memory, Digit Symbol Coding, Spatial Span), (2) search (Visual Search, TMT-A, TMT-B, Letter Cancellation); (3) Digit Span; (4) Arithmetic; and (5) Sustained Attention (GradCPT). Confirmatory analysis in 279 held-out participants showed that this model fit better than competing models. A hierarchical model where a general cognitive factor was imposed above the five specific factors fit as well as the model without the general factor. We conclude that Digit Span and Arithmetic tests should not be classified as attention tests. Digit Symbol Coding and Spatial Span tap attentional capacity, while TMT-A, TMT-B, and Letter Cancellation tap search (or attention-shifting) ability. These five tests can be classified as attention tests.

Wound healing after skin injury is a dynamic and highly coordinated process involving a well-orchestrated series of phases, including hemostasis, inflammation, proliferation, and tissue remodeling. Epigenetic regulation refers to genome-wide molecular events, including DNA methylation, histone modification, and non-coding RNA regulation, represented by microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Epigenetic regulation is pervasively occurred in the genome and emerges as a new role in gene expression at the post-transcriptional level. Currently, it is well-recognized that epigenetic factors are determinants in regulating gene expression patterns, and may provide evolutionary mechanisms that influence the wound microenvironments and the entire healing course. Therefore, this review aims to comprehensively summarize the emerging roles and mechanisms of epigenetic remodeling in wound healing. Moreover, we also pose the challenges and future perspectives related to epigenetic modifications in wound healing, which would bring novel insights to accelerated wound healing.

PurposeBreast cancer (BC) is the most common malignancy and the leading cause of cancer-related death among women worldwide. Early detection, treatment, and metastasis monitoring are very important for the prognosis of BC patients. Therefore, effective biomarkers need to be explored to help monitor the prognosis of BC patients and guide treatment decisions.MethodsIn this study, the relationship between CCDC69 expression levels and tumor clinical characteristics were analyzed using RNA-seq information in BC samples from the TCGA database. Kaplan-Meier survival analysis was performed to analyze the prognostic value of CCDC69 in BC patients. Besides, gene enrichment analysis in BC samples was used to confirm the main function of CCDC69 in BC. The correlation between the expression of CCDC69 and the number of tumor-infiltrating lymphocytes was confirmed by interaction analysis of TIMER and GEPIA.ResultsThe results showed that CCDC69 expression was significantly lower in cancer samples than in normal tissues, and was significantly lower in highly invasive BC than in carcinoma in situ. Meanwhile, low levels of CCDC69 were associated with a further poor prognosis. CDCC69 expression was positively correlated with the amount of different tumor-infiltrating lymphocytes. Mechanically, it could be presumed that the low expression of CCDC69 in BC might be caused by hypermethylation of the promoter region.ConclusionsSummarily, CDCC69 could be used as a potential biomarker to predict the prognosis of BC and the sensitivity to immunotherapy such as PD-1/PD-L1 checkpoint inhibitors.

Study region: This study is carried out across a 142,000 km2 area within the Alberta Oil Sands Region (AOSR), Alberta, Canada. Study focus: Groundwater quality data for the AOSR are compiled and interpreted to provide information on regional water quality to inform groundwater monitoring and land use planning. A database of 546 water quality parameters measured between 1958 and 2015 from 5118 water wells is compiled, cleaned, and analyzed by hydrostratigraphic unit (HSU). New hydrologic insights for the region: Baseline water quality conditions were found to vary in the 12 main HSU’s, with wide ranges in total dissolved solids and geochemical facies, reflecting variable lithology and geochemical processes. Median concentrations for multiple parameters exceeded “interim trigger values” under consideration by government regulators. Statistically significant temporal changes in water quality were detected in the 2000’s in isolated areas of Surficial Sands aquifer, the Cretaceous and Devonian formations in the North Athabasca Oil Sands, and in Quaternary aquifers in the South Athabasca Oil Sands and Cold Lake Beaver River. Temporal anomalies occur in areas with enhanced vertical connectivity due to the presence of buried channels, incised rivers, or where the Colorado Group is thin or completely absent. The compiled dataset highlights the role of geochemical data in identifying aquifer connectivity and monitoring priority. Lack of publicly available data for key aquifers near some mining areas are noted.

Summary:. The angular branch of the thoracodorsal artery and the periosteal branches of the circumflex scapular artery can be easily injured while harvesting a chimeric scapular flap. Thus, we reported the use of 3D printed scapular models using CT angiography to prepare inexpensive surgical guides from autoclavable dental silicone impressions for scapular flap harvest. Mandibular and scapular models were prepared using a 3D printer for 11 patients undergoing chimeric scapular flap transfer following mandibular resection. During preoperative simulation surgery, we molded dental silicone accordingly with scapular models to produce surgical cutting guides. Six men (54.5%) and five women (45.5%) were included. The average age of patients was 65.4 years. Fourteen bone units were reconstructed as three patients needed two bone segments (27.3%) whereas eight patients required reconstruction of one bone segment (72.7%). The mean flap harvest time and total surgical time were 52.1 min and 633.8 min, respectively. The mean duration for osteotomies and bone plate fixation was 26.2 min. The difference between the length of the preoperative surgical model (64.92 mm) and the postoperative 3D-CT measurements (64.48 mm) was not statistically significant (0.95 mm, P = 0.397). No injuries were caused to the angular and periosteal vessels. Four patients exhibited donor-site seroma (36.4%). The cost of the dental silicone for surgical guide was only $5 per patient. Dental silicone-based surgical guides help minimize the risk of vascular injury while harvesting chimeric scapular flaps. The osteotomies were performed with precision and in a time-efficient manner.

Abstract Breast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major health concern globally. Genomic epidemiology is an important tool to assess the pandemic of coronavirus disease 2019 (COVID-19). Several mutations have been reported by genome analysis of the SARS-CoV-2. In the present study, we investigated the mutational and phylogenetic analysis of 30 whole-genome sequences for the virus's genomic characteristics in the specimens collected in the early phase of the pandemic (March–June, 2020) and the sudden surge of local transmission (August–September, 2020). The four samples in the early phase of infection were B.6 lineage and located within a clade of the samples collected at the same time in Singapore and Malaysia, while five returnees by rescue flights showed the lineage B. 1.36.1 (three from India), B.1.1 (one from India) and B.1.80 (one from China). However, there was no evidence of local spread from these returnees. Further, all 19 whole-genome sequences collected in the sudden surge of local transmission showed lineage B.1.36. The surge of the second wave on SARS-CoV-2 infection was linked to the single-introduction of a variant (B.1.36) that may result from the strict restriction of international travel and containment efforts. These genomic data provides the useful information to disease control and prevention strategy.

Drug interactions between anti-tuberculosis and immunosuppressive medications after renal transplantation are a common problem in Myanmar. The efficacy of both types of drugs can be reduced during the treatment period, which can lead to graft failure and flare-ups of infection. Drug adjustments, with frequent monitoring and close follow-up, are crucial in this period. Ketoconazole decreases tacrolimus metabolism by inhibiting cytochrome P450-3A5 enzymes and P-glycoprotein. It is cost effective and has been frequently used to reduce the dose and cost of tacrolimus. Here, we report the case of a 56-year-old male renal transplant recipient with anti-tuberculosis medications.

In the current study, we aimed to explore the correlation between TRIM27 and breast cancer prognosis, as well as the functions of TRIM27 in breast cancer and their underlying mechanisms. Bioinformatics analyses were used to examine the correlation between TRIM27 and breast cancer prognosis. Moreover, TRIM27 knockdown and overexpression in breast cancer cells were performed to investigate its functions in breast cancer. Tamoxifen (TAM) was applied to evaluate the influence of TRIM27 on chemoresistance of breast cancer cells, while co-immunoprecipitation (coIP) was performed to identify the E3 ubiquitin ligase capability of TRIM27. High expression of TRIM27 was found in non-triple-negative breast cancer (non-TNBC) tumor tissues and was positively correlated with the mortality of non-TNBC patients. Moreover, TRIM27 could suppress non-TNBC cell apoptosis and senescence, promote cell viability and tumor growth, counteract the anti-cancer effects of TAM, and mediate ubiquitination of p21. In addition, EP300 could enhance the expression of TRIM27 and its transcription promoter H3K27ac. TRIM27, through ubiquitination of p21, might serve as a prognostic biomarker for non-TNBC prognosis. TRIM27 functions as a novel oncogene in non-TNBC cellular processes, especially suppressing cell senescence and interfering with non-TNBC chemoresistance.

Unregulated university cafeterias may be serving food and beverages high in fat or sugar. Traffic light labelling (TLL) has been able to guide students in making healthier choices. Therefore, the aim of this study was to assess the healthiness level of food and beverages served in university cafeterias by profiling it against TLL and calorie density to evaluate student’s perception towards the implementation of TLL. This pilot observational study was conducted in three universities; two public university and one private institution within Klang Valley. A total of 166 foods and beverages were analysed for calories, fat, saturated fat, sodium, and sugar by using a nutritional software, Nutritionist Pro (TM). Analysed data for each food/beverage were further profiled into TLL and calorie density by using an excel spreadsheet. Food and beverages analysed were those sold in canteen and cafeterias combined those frequently consumed, reported in a food frequency questionnaire (FFQ). A total of 192 students completed a questionnaire containing three sections: personal profile, a short FFQ of their usual intake and their perception towards implementation of TLL in their institutions. 8.1% of all food items were categorised as green (healthy food), whereas 41.9% were amber (moderately healthy food), and 50% were red (unhealthy food). Almost half of the beverages (46.7%) were found to be unhealthy. However, when all foods were profiled for calorie density, more than half (61.8%) were categorised as moderately healthy food. In addition, most of the respondents (88%) showed a positive perception towards the implementation of TLL in the cafeteria. A large number of meals sold in two universities cafeterias were unhealthy and requires dietary modification. TLL implementation was beneficial for tertiary students as it may help guide the students to choose healthier options of cooked meals and packaged foods and beverages.

Abstract Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.

Abstract Background Hepatitis B virus (HBV) infections are a severe health concern worldwide. HBV is a DNA virus with a rapid rate of mutation. Based on heterogeneity of the nucleotide sequence, the HBV strains are divided into nine genotypes, each with a characteristic geographical distribution. Identifying and tracking alterations of HBV genotypes is important in epidemiological and transmission studies, and contributes to predicting the risk for development of severe liver disease and response to antiviral treatment. The present study was undertaken to detect HBV genotypes and sub-genotypes in the general population of different states and regions in Myanmar. Methods In 2015, a total of 5547 adults of the general population, residing in seven states, seven regions and the Nay Pyi Taw Union Territory, were screened for Hepatitis B Surface antigen (HBsAg) by the immunochromatographic test (ICT). Of the 353 HBsAg positive samples, the HBVDNA was identified using polymerase chain reactions (PCR) targeting the DNA sequences encoding the Pre-S region. A total of 153 PCR positive samples were subsequently subjected to genotyping by partial genome sequencing in both directions. The resulting sequences were then edited, aligned, and compared with reference sequences using the National Centre for Biotechnology Information (NCBI) web-based genotyping tool. Results Three HBV genotypes (HBV genotype B, genotype C and genotype D) were detected in Myanmar, of which genotype HBV genotype C (66.7%) was the most prevalent, followed by HBV genotype D (32%) and HBV genotype B (1.3%). Sub-genotyping revealed a total of 7 variants within the B, C and D genotypes: 2 (B4 and B5) in HBV genotype B, 3 (C1, C5 and C7) in HBV genotype C, and 2 (D3 and D6) in HBV genotype D. Conclusion HBV genotype C, sub-genotype C1 was predominantly distributed in all states and regions of Myanmar. This study is the first report on the nationwide distribution of HBV genotypes and sub-genotypes in Myanmar. We believe our findings will enable huge support for the hepatitis disease surveillance program, since HBV infection is one of the National Priority Diseases in Myanmar.

Background : Renal transplant is an effective treatment option for end-stage kidney disease and tacrolimus is one of the most commonly used immunosuppressant drugs in renal transplant patients. Tacrolimus is a substrate of cytochrome P450 3A5 (CYP3A5), and a narrow therapeutic index and large inter-individual variability. The objective of this study was to determine the frequency of CYP3A5*3 polymorphism and its effect on the pharmacokinetics of tacrolimus in post-renal transplant patients at Mandalay General Hospital. Methods : Three different genotypes of CYP3A5 were determined by polymerase chain reaction-restriction fragment length polymorphism in 54 post-renal transplant recipients. Tacrolimus trough concentrations (Ctrough) were measured by enzyme multiplied immunoassay technique following method validation. The apparent clearance (CL/F) was calculated from measured Ctrough. Results : The frequency of CYP3A5*1 allele was 0.24 and that of CYP3A5*3 allele was 0.76 in the study sample. There were a total of 33 CYP3A5 non-expressors (patients with CYP3A5*3/*3 genotype) and 21 CYP3A5 expressors (patients with CYP3A5*1/*1 or CYP3A5*1/*3 genotype), respectively. CL/F was significantly lower in the non-expressor group than in the expressor group (mean±standard deviation, 12.53±5.28 vs. 21.22±5.95 L/hr; P

Salt spray splashing on the structural surfaces of ships is a common difficulty in polar navigation. In this paper, experiments are designed to study the variation in the growth peak of pure water droplets on the surface of a hydrophobic coating with a contact angle of 90°, and the numerical simulation method is verified according to the experiment. The variation in the growth peak calculated by the numerical simulation is consistent with the experiment, and the calculation error of the freezing time obtained by numerical simulation is less than 10% of that of the experiment. The freezing processes of droplets with salinity levels of 0, 10, 20, 30, 40, and 10 μL on the surfaces of the hydrophilic, hydrophobic, and super hydrophobic plates are studied. The freezing time of the droplets is calculated, along with the effects of the wall temperature, surface contact angle, and salinity on the freezing time and freezing process of the droplets. The results show that the freezing time increased dramatically with increasing salinity. The influence of the contact angle and substrate temperature on the freezing process was also concentrated. All these results contribute to a better understanding of the icing mechanism on marine surfaces.

Obesity is associated with energy metabolic disturbance and is caused by long-term excessive energy storage in white adipose tissue (WAT). The WAT browning potentially reduces excessive energy accumulation, contributing an attractive target to combat obesity. As a pivotal regulator of cell growth, the transcription factor E2F1 activity dysregulation leads to metabolic complications. The regulatory effect and underlying mechanism of E2F1 knockout on WAT browning, have not been fully elucidated. To address this issue, in this study, the in vivo adipose morphology, mitochondria quantities, uncoupling protein 1 (UCP-1), autophagy-related genes in WAT of wild-type (WT) and E2F1–/– mice were detected. Furthermore, we evaluated the UCP-1, and autophagy-related gene expression in WT and E2F1–/– adipocyte in vitro. The results demonstrated that E2F1 knockout could increase mitochondria and UCP-1 expression in WAT through autophagy suppression in mice, thus promoting WAT browning. Besides, adipocytes lacking E2F1 showed upregulated UCP-1 and downregulated autophagy-related genes expression in vitro. These results verified that E2F1 knockout exerted effects on inducing mice WAT browning through autophagy inhibition in vivo and in vitro. These findings regarding the molecular mechanism of E2F1-modulated autophagy in controlling WAT plasticity, provide a novel insight into the functional network with the potential therapeutic application against obesity.

Breast cancer (BC) is the most frequent malignancy and is ranking the leading cause of cancer-related death among women worldwide. At present, BC is still an intricate challenge confronted with high invasion, metastasis, drug resistance, and recurrence rate. Exosomes are membrane-enclosed extracellular vesicles with the lipid bilayer and recently have been confirmed as significant mediators of tumor cells to communicate with surrounding cells in the tumor microenvironment. As very important orchestrators, non-coding RNAs (ncRNAs) are aberrantly expressed and participate in regulating gene expression in multiple human cancers, while the most reported ncRNAs within exosomes in BC are microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Notably, ncRNAs containing exosomes are novel frontiers to shape malignant behaviors in recipient BC cells such as angiogenesis, immunoregulation, proliferation, and migration. It means that tumor-derived ncRNAs-containing exosomes are pluripotent carriers with intriguing and elaborate roles in BC progression via complex mechanisms. The ncRNAs in exosomes are usually excavated based on specific de-regulated expression verified by RNA sequencing, bioinformatic analyses, and PCR experiments. Here, this article will elucidate the recent existing research on the functions and mechanisms of tumor-derived exosomal miRNA, lncRNA, circRNA in BC, especially in BC cell proliferation, metastasis, immunoregulation, and drug resistance. Moreover, these tumor-derived exosomal ncRNAs that existed in blood samples are proved to be excellent diagnostic biomarkers for improving diagnosis and prognosis. The in-depth understanding of tumor-derived exosomal ncRNAs in BC will provide further insights for elucidating the BC oncogenesis and progress and exploring novel therapeutic strategies for combating BC.

The metastasis and poor prognosis are still regarded as the main challenge in the clinical treatment of breast cancer (BC). Both N6-methyladenosine (m6A) modification and lncRNAs play vital roles in the carcinogenesis and evolvement of BC. Considering the unknown association of m6A and lncRNAs in BC, this study therefore aims to discern m6A-related lncRNAs and explore their prognostic value in BC patients. Firstly, a total of 6 m6A-related lncRNAs were screened from TCGA database and accordingly constructed a prognostic-predicting model. The BC patients were then divided into high-risk and low-risk groups dependent on the median cutoff of risk score based on this model. Then, the predictive value of this model was validated by the analyses of cox regression, Kaplan-Meier curve, ROC curve, and the biological differences in the two groups were validated by PCA, KEGG, GSEA, immune status as well as in vitro assay. Finally, we accordingly constructed a risk prognostic model based on the 6 identified m6A-related lncRNAs, including Z68871.1, AL122010.1, OTUD6B-AS1, AC090948.3, AL138724.1, EGOT. Interestingly, the BC patients were divided into the low-risk and high-risk groups with different prognoses according to the risk score. Notably, the risk score of the model was an excellent independent prognostic factor. In the clinical sample validation, m6A regulatory proteins were differentially expressed in patients with different risks, and the markers of tumor-associated macrophages and m6A regulators were co-localized in high-risk BC tissues. This well-validated risk assessment tool based on the repertoire of these m6A-related genes and m6A-related lncRNAs, is of highly prognosis-predicting ability, and might provide a supplemental screening method for precisely judging BC prognosis.

Autologous fat grafting (AFG) is widely regarded as an important method for breast reconstruction after mastectomy among breast cancer (BC) patients. FTY720 has been proved to affect macrophage polarization and improve the sensitivity of postoperative BC treatment. This study aimed to explore FTY720 function and underlying mechanism in fat transplantation. The C57BL/6 J mice that received AFG were randomly divided into two groups treated with saline and FTY720, respectively. The fat graft samples were obtained at week 1, 2, 4, and 12 post-transplantation. Graft volumes, graft structures, M2 macrophages, and STAT3 protein expression were estimated by histological examination, immunofluorescence, flow cytometry, and western blot, respectively. In vitro, mouse preadipocytes were stimulated with FTY720 treated-M2 macrophages conditioned medium (FTY720-M2-CM) to evaluate the adipogenesis effect. The level of adipogenic mRNA expression in preadipocytes was detected by RT-PCR. The in vivo results showed that FTY720 treatment significantly enhanced the fat graft retention, structure integrity, and neovascularization, indicating the potential of FTY720 in improving graft survival. The histology results showed more polarized M2 macrophage presented in the FTY720 group. In the in vitro assay, after FTY720-M2-CM treatment, the 3T3-L1 preadipocytes showed the increased triglyceride content and adipogenic mRNA expression, including FABP4, C/EBP-α, Adipoq, and PPARγ. Furthermore, FTY720 treatment up-regulated the expression level of M2 biomarker CD206, Arg-1, Fizz-1, which could be weakened by the STAT3 inhibitor. Together, this study confirmed the potential efficacy of FTY720 in improving graft survival in the AFG model, possibly mediated by polarizing macrophages to M2 type through activating the STAT3 pathway.

Tolerance breeding through genetic engineering, sequence and omics analyses, and gene identification processes are widely used to synthesize biofuels. The majority of related mechanisms have been shown to yield endogenous genes with high expression. However, the process was time-consuming and labor-intensive, meaning there is a need to address the problems associated with the low-throughput screening method and significant time and money consumption. In this study, a combination of the limit screening method (LMS method) and product-tolerance engineering was proposed and applied. The Escherichia coli MG1655 genomic DNA library was constructed using the shotgun method. Then, the cultures were incubated at concentrations of 0.25%, 0.5%, 0.75% and 1.0% of pinene with different inhibitory effects. Finally, the genes acrB, flgFG, motB and ndk were found to be associated with the enhanced tolerance of E. coli to pinene. Using the I-SceI cleavage system, the promoters of acrB, flgFG and ndk genes were replaced with P37. The final strain increased the production of pinene from glucose by 2.1 times.

Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

Abstract The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte‐specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine‐induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy‐related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.

Abstract Background For the past decades, Malaysia has seen an increased prevalence of overweight and obesity which leads to significant health threats. Physical activity is beneficial in maintaining healthy body weight. The objective of this study was to measure physical activity of adults in Malaysia using objective measurement (accelerometer) and self-reported methods, as well as to determine their associations with (body mass index (BMI) and waist circumference (WC) measurements. Methods Four-hundred and ninety Malaysian adults (n = 490) aged 20 to 65 years old participated in this cross-sectional study. Their body weight, height, and WC measurements were measured according to standard procedures. Physical activity was assessed objectively with accelerometers for five to seven consecutive days. The International Physical Activity Questionnaire (IPAQ) was used to estimate the amount of time spent on various domains of physical activity. Mixed models were used to determine the associations between physical activity variables and both BMI and WC. Results The mean value of objectively measured moderate-to-vigorous physical activity (MVPA) was 13.5 min per day, in which male participants recorded a significantly higher amount of time compared to females. On the other hand, the mean self-reported total physical activity was 380 min per week; male participants reported a significantly higher amount of time on physical activity in the occupation/work and leisure/recreation domains while female participants spent significantly more time in the domestic/household chores domain. We also observed that the mean values of objectively measured total MVPA, self-reported time spent on walking for leisure/recreation, and total time amount of time spent on MVPA for leisure/recreation were significantly higher among participants with BMI of less than 25 kg/m2. The final statistical model yielded a significant negative association between objectively measured total MVPA and BMI, but not with WC measurement. No significant association was reported between self-reported total physical activity with BMI and WC measurement. Conclusions Objectively measured MVPA was inversely associated with BMI, but not WC measurement. No significant association was observed between self-reported total physical activity and physical activity time measures across domains with both BMI and WC measurement.

Abstract Background Mortality indicators are essential for monitoring population health. Although Malaysia has a functional death registration system, the quality of information on causes of death still needs improvement, since approximately 30% of deaths are classified to poorly defined causes. This study was conducted to verify registered causes in a sample of deaths in 2013 and utilise the findings to estimate cause-specific mortality indicators for Malaysia in 2013. Methods This is a cross-sectional study involving a nationally representative sample of 14,497 deaths distributed across 19 districts. Registered causes of deaths were verified using standard medical record review protocols for hospital deaths, and locally adapted international standard verbal autopsy procedures for deaths outside hospitals. The findings were used to measure the validity and reliability of the registration data, as well as to establish plausible cause-specific mortality fractions for hospital and non-hospital deaths, which were subsequently used as the basis for estimating national cause-specific mortality indicators. Results The overall response rate for the study was 67%. Verified causes of 5041 hospital deaths and 3724 deaths outside hospitals were used to derive national mortality estimates for 2013 by age, sex and cause. The study was able to reclassify most of the ill-defined deaths to a specific cause. The leading causes of deaths for males were Ischaemic Heart Disease (15.4%), Cerebrovascular diseases (13.7%), Chronic Obstructive Pulmonary Disease (8.5%) and Road Traffic Accident (8.0%). Among females, the leading causes were Cerebrovascular diseases (18.3%), Ischaemic Heart Disease (12.7%), Lower Respiratory Infections (11.5%) and Diabetes Mellitus (7.2%). Conclusions Investigation of registered causes of death using verbal autopsy and medical record review yielded adequate information to enable estimation of cause-specific mortality indicators in Malaysia. Strengthening the national mortality statistics system must be made a priority as it is a core data source for policy and evaluation of the public health and healthcare sectors in Malaysia.

We present a case on adrenal schwannomas. The CT shows enhancement of distal adrenal gland lesion. We named it rabbit tail sign. Adrenal schwannomas are rare and presents a very small proportion of retroperitoneal schwannomas. It tends to be misdiagnosed because of lacking characteristics clinical presentations and CT features. And there is debate about its origination. The rabbit tail sign of distal adrenal gland is one typical radiographic feature of adrenal schwannomas. It also suggests the tumor may originate from dominate nerve of adrenal medulla.

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

Autologous fat transplantation is widely regarded as an increasingly popular method for augmentation or reshaping applications in soft tissue defects. Although the fat transplantation is of simple applicability, low donor site morbidity and excellent biocompatibility, the clinical unpredictability and high resorption rates of the fat grafts remain an inevitable problem. In the sites of fat transplantation, the most essential components are the adipocyte and adipose-derived stem cells (ADSCs). The survival of adipocytes is the direct factor determining fat retention. The efficacy of fat transplantation is reduced by fat absorption and fibrosis due to the inadequate blood flow, adipocyte apoptosis and fat necrosis. ADSCs, a heterogeneous mixture of cells in adipose tissue, are closely related to tissue survival. ADSCs exhibit the ability of multilineage differentiation and remarkable paracrine activity, which is crucial for graft survival. This article will review the recent existing research on the mechanisms of adipocytes and ADSCs in fat transplantation, especially including adipocyte apoptosis, mature adipocyte dedifferentiation, adipocyte browning, ADSCs adipogenic differentiation and ADSCs angiogenesis. The in-depth understanding of the survival mechanism will be extremely valuable for achieving the desired filling effects.