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The interaction between programmed cell death ligand 1 (PD-L1), which is expressed on the surface of tumor cells, and programmed cell death 1 (PD-1), which is expressed on T cells, impedes the effective activation of tumor antigen-specific T cells, resulting in the evasion of tumor cells from immune-mediated killing. Blocking the PD-1/PD-L1 signaling pathway has been shown to be effective in preventing tumor immune evasion. PD-1/PD-L1 blocking antibodies have garnered significant attention in recent years within the field of tumor treatments, given the aforementioned mechanism. Furthermore, clinical research has substantiated the efficacy and safety of this immunotherapy across various tumors, offering renewed optimism for patients. However, challenges persist in anti-PD-1/PD-L1 therapies, marked by limited indications and the emergence of drug resistance. Consequently, identifying additional regulatory pathways and molecules associated with PD-1/PD-L1 and implementing judicious combined treatments are imperative for addressing the intricacies of tumor immune mechanisms. This review briefly outlines the structure of the PD-1/PD-L1 molecule, emphasizing the posttranslational modification regulatory mechanisms and related targets. Additionally, a comprehensive overview on the clinical research landscape concerning PD-1/PD-L1 post-translational modifications combined with PD-1/PD-L1 blocking antibodies to enhance outcomes for a broader spectrum of patients is presented based on foundational research. [ABSTRACT FROM AUTHOR]

Backgrounds: The respiratory microbiota and radiomics correlate with the disease severity and prognosis of chronic obstructive pulmonary disease (COPD). We aim to characterize the respiratory microbiota and radiomics features of COPD patients and explore the relationship between them. Methods: Sputa from stable COPD patients were collected for bacterial 16 S rRNA gene sequencing and fungal Internal Transcribed Spacer (ITS) sequencing. Chest computed tomography (CT) and 3D-CT analysis were conducted for radiomics information, including the percentages of low attenuation area below − 950 Hounsfield Units (LAA%), wall thickness (WT), and intraluminal area (Ai). WT and Ai were adjusted by body surface area (BSA) to WT/ and Ai/BSA, respectively. Some key pulmonary function indicators were collected, which included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion lung carbon monoxide (DLco). Differences and correlations of microbiomics with radiomics and clinical indicators between different patient subgroups were assessed. Results: Two bacterial clusters dominated by Streptococcus and Rothia were identified. Chao and Shannon indices were higher in the Streptococcus cluster than that in the Rothia cluster. Principal Co-ordinates Analysis (PCoA) indicated significant differences between their community structures. Higher relative abundance of Actinobacteria was detected in the Rothia cluster. Some genera were more common in the Streptococcus cluster, mainly including Leptotrichia, Oribacterium, Peptostreptococcus. Peptostreptococcus was positively correlated with DLco per unit of alveolar volume as a percentage of predicted value (DLco/VA%pred). The patients with past-year exacerbations were more in the Streptococcus cluster. Fungal analysis revealed two clusters dominated by Aspergillus and Candida. Chao and Shannon indices of the Aspergillus cluster were higher than that in the Candida cluster. PCoA showed distinct community compositions between the two clusters. Greater abundance of Cladosporium and Penicillium was found in the Aspergillus cluster. The patients of the Candida cluster had upper FEV1 and FEV1/FVC levels. In radiomics, the patients of the Rothia cluster had higher LAA% and WT/ than those of the Streptococcus cluster. Haemophilus, Neisseria and Cutaneotrichosporon positively correlated with Ai/BSA, but Cladosporium negatively correlated with Ai/BSA. Conclusions: Among respiratory microbiota in stable COPD patients, Streptococcus dominance was associated with an increased risk of exacerbation, and Rothia dominance was relevant to worse emphysema and airway lesions. Peptostreptococcus, Haemophilus, Neisseria and Cutaneotrichosporon probably affected COPD progression and potentially could be disease prediction biomarkers. [ABSTRACT FROM AUTHOR]

Background and objectives: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. Methods: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. Results: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05–6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46–2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11–0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02–13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97–3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48–5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10–3.10). Conclusion: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. Trial registration: PROSPERO: CRD42022379276. [ABSTRACT FROM AUTHOR]

This document is a retraction note from the journal Cancer Cell International. The article titled "Circular RNA ITCH suppressed prostate cancer progression by increasing HOXB13 expression via spongy miR-17-5p" has been retracted at the request of the corresponding author. The retraction was prompted by concerns about image overlap in several figures of the article. The authors were unable to retrieve the data from a third-party biological company, leading to a loss of confidence in the presented data. The retraction was agreed upon by all authors. [Extracted from the article]

Background: Agitation is common in subarachnoid hemorrhage (SAH), and sedation with midazolam, propofol and dexmedetomidine is essential in agitation management. Previous research shows the tendency of dexmedetomidine and propofol in improving long-term outcome of SAH patients, whereas midazolam might be detrimental. Brain metabolism derangement after SAH might be interfered by sedatives. However, how sedatives work and whether the drugs interfere with patient outcome by altering cerebral metabolism is unclear, and the comprehensive view of how sedatives regulate brain metabolism remains to be elucidated. Methods: For cerebrospinal fluid (CSF) and extracellular space of the brain exchange instantly, we performed a cohort study, applying CSF of SAH patients utilizing different sedatives or no sedation to metabolomics. Baseline CSF metabolome was corrected by selecting patients of the same SAH and agitation severity. CSF components were analyzed to identify the most affected metabolic pathways and sensitive biomarkers of each sedative. Markers might represent the outcome of the patients were also investigated. Results: Pentose phosphate pathway was the most significantly interfered (upregulated) pathway in midazolam (p = 0.0000107, impact = 0.35348) and propofol (p = 0.00000000000746, impact = 0.41604) groups. On the contrary, dexmedetomidine decreased levels of sedoheptulose 7-phosphate (p = 0.002) and NADP (p = 0.024), and NADP is the key metabolite and regulator in pentose phosphate pathway. Midazolam additionally augmented purine synthesis (p = 0.00175, impact = 0.13481) and propofol enhanced pyrimidine synthesis (p = 0.000203, impact = 0.20046), whereas dexmedetomidine weakened pyrimidine synthesis (p = 0.000000000594, impact = 0.24922). Reduced guanosine diphosphate (AUC of ROC 0.857, 95%CI 0.617–1, p = 0.00506) was the significant CSF biomarker for midazolam, and uridine diphosphate glucose (AUC of ROC 0.877, 95%CI 0.631–1, p = 0.00980) for propofol, and succinyl-CoA (AUC of ROC 0.923, 95%CI 0.785–1, p = 0.000810) plus adenosine triphosphate (AUC of ROC 0.908, 95%CI 0.6921, p = 0.00315) for dexmedetomidine. Down-regulated CSF succinyl-CoA was also associated with favorable outcome (AUC of ROC 0.708, 95% CI: 0.524–0.865, p = 0.029333). Conclusion: Pentose phosphate pathway was a crucial target for sedatives which alter brain metabolism. Midazolam and propofol enhanced the pentose phosphate pathway and nucleotide synthesis in poor-grade SAH patients, as presented in the CSF. The situation of dexmedetomidine was the opposite. The divergent modulation of cerebral metabolism might further explain sedative pharmacology and how sedatives affect the outcome of SAH patients. [ABSTRACT FROM AUTHOR]

Background: Migration of fish bones into abdominal para-aortic tissue after penetrating the junction of 3rd and 4th part of duodenum is incredibly rare.Case Presentation: A 68-year-old man was admitted to our hospital with persistent colic in the lower abdomen after eating fish two weeks ago. Abdominal computed tomography (CT) scan showed High density streaks along the anterior and lower edges of the 3rd part of duodenum with peripheral exudation and localized peritonitis. Esophagogastroduodenoscopy didn't find foreign bodies and perforations in the digestive tract. Laparoscopic surgery and intraoperative endoscopy were made to detect foreign bodies and perforation site was found. After transition to open surgery, the fish bone was found in abdominal para-aortic tissue and removed without complications. Postoperative recovery is smooth, and the patient resumed normal diet and was discharged.Conclusions: It is difficult to choose a treatment plan for foreign bodies at the 3rd part of the duodenum, because it is difficult to judge the damage caused by the foreign body to the intestine and the positional relationship with the surrounding important organs. Conservative treatment or surgical treatment both have huge risks. The handling of this situation will extremely test the psychology, physical strength and professional experience of the surgeon. [ABSTRACT FROM AUTHOR]

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovarian stimulation. Prevention and early recognition of OHSS are important to ensure patient safety.Case Presentation: In this case, we reported a patient who underwent controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF). All embryos were cryopreserved to reduce possible OHSS. However, OHSS still occurred after the patient had a frozen-thawed embryo transfer (FET) with hormone replacement therapy (HRT) and obtained a dichorionic diamniotic triplet pregnancy. After multifetal pregnancy reduction (MFPR) and supportive treatment, all the symptoms regressed.Conclusions: Prompt recognition of OHSS, especially in patients who have no history of ovulation induction and fresh embryo transfer, is very important. Multiple pregnancies may lead to severe OHSS because of the high level of human chorionic gonadotropin (hCG) in the early stages. We suggest that a single embryo transfer may be necessary and beneficial for patients. [ABSTRACT FROM AUTHOR]

Background: Surgery, as one of the main diagnostic and treatment methods, is a routine work in medical settings. Patients undergoing surgery often experience acute procedure anxiety due to uncertainty. There is ample evidence showing that uncertainty is a risk factor for the acute procedure anxiety in surgical patients. However, little is known about the psychological processes mediating this relationship. Therefore, this study aims to evaluate resilience as a mediator of the association between uncertainty and anxiety. Methods: A population-based cross-sectional survey with a convenience sampling method was conducted, involving 243 surgical patients in Jiaxing, Zhejiang province of China was carried out. Relevant data were collected by self-reporting questionnaires, including demographic characteristics questionnaire, Amsterdam Preoperative Anxiety and Information Scale (APAIS-C), Mishel's Illness Uncertainty Scale (MUIS), Connor-Davidson Resilience Scale (CD-RISC). Pearson correlation analysis was employed to examine correlations between various variables. A path model was used to assess the mediation effect of resilience with respect to uncertainty and acute procedure anxiety. Results: In the path model, uncertainty have an indirect effect on acute procedure anxiety through resilience. The results suggest that resilience has a mediating role in uncertainty and acute procedure anxiety among surgical patients. Conclusions: These findings call for the development of interventions targeting the role of resilience in effectively predicting and preventing acute procedure anxiety and uncertainty among surgical patients. [ABSTRACT FROM AUTHOR]

Background: Recent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting that glucose reduction by energy restriction (calorie restriction or short-term fasting) may has a significant impact on TAMs. The purpose of this study is to verify the effect of fasting-mimicking diet (FMD) on TAMs, and to determine whether FMD synergizes with anti-angiogenic drug apatinib via TAMs. Methods: The effect of FMD on TAMs and its synergistic effects with apatinib were observed using an orthotopic mouse breast cancer model. An in vitro cell model, utilizing M2 macrophages derived from THP-1 cell line, was intended to assess the effects of low glucose on TAMs under hypoxic and normoxic conditions. Bioinformatics was used to screen for potential mechanisms of action, which were then validated both in vivo and in vitro. Results: FMD significantly inhibit the pro-tumor function of TAMs in vivo and in vitro, with the inhibitory effect being more pronounced under hypoxic conditions. Additionally, the combination of FMD-mediated TAMs inhibition with apatinib results in synergistic anti-tumor activity. This effect is partially mediated by the downregulation of CCL8 expression and secretion by the mTOR-HIF-1α signaling pathway. Conclusions: These results support further clinical combination studies of FMD and anti-angiogenic therapy as potential anti-tumor strategies. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell carcinoma (ccRCC) is associated with a high prevalence of cancer-related deaths. The survival rates of patients are significantly lower in late-stage ccRCC than in early-stage ccRCC, due to the spread and metastasis of late-stage ccRCC, surgery has not reached the goal of radical cure, and the effect of traditional radiotherapy and chemotherapy is poor. Thus, it is crucial to accurately assess the prognosis and provide personalized treatment at an early stage in ccRCC. This study aims to develop an efficient nomogram model for stratifying and predicting the survival of ccRCC patients based on tumor stage. Methods: We first analyzed the microarray expression data of ccRCC patients from the Gene Expression Omnibus (GEO) database and categorized them into two groups based on the disease stage (early and late stage). Subsequently, the GEO2R tool was applied to screen out the genes that were highly expressed in all GEO datasets. Finally, the clinicopathological data of the two patient groups were obtained from The Cancer Genome Atlas (TCGA) database, and the differences were compared between groups. Survival analysis was performed to evaluate the prognostic value of candidate genes (PSAT1, PRAME, and KDELR3) in ccRCC patients. Based on the screened gene PSAT1 and clinical parameters that were significantly associated with patient prognosis, we established a new nomogram model, which was further optimized to a single clinical variable-based model. The expression level of PSAT1 in ccRCC tissues was further verified by qRT-PCR, Western blotting, and immunohistochemical analysis. Results: The datasets GSE73731, GSE89563, and GSE150404 identified a total of 22, 89, and 120 over-expressed differentially expressed genes (DEGs), respectively. Among these profiles, there were three genes that appeared in all three datasets based on different stage groups. The overall survival (OS) of late-stage patients was significantly shorter than that of early-stage patients. Among the three candidate genes (PSAT1, PRAME, and KDELR3), PSAT1 was shown to be associated with the OS of patients with late-stage ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, neoadjuvant therapy, and PSAT1 level were significantly associated with patient prognosis. The concordance indices were 0.758 and 0.725 for the 3-year and 5-year OS, respectively. The new model demonstrated superior discrimination and calibration compared with the single clinical variable model. The enhancer PSAT1 used in the new model was shown to be significantly overexpressed in tissues from patients with late-stage ccRCC, as demonstrated by the mRNA level, protein level, and pathological evaluation. Conclusion: The new prognostic prediction nomogram model of PSAT1 and clinicopathological variables combined was thus established, which may provide a new direction for individualized treatment for different-stage ccRCC patients. [ABSTRACT FROM AUTHOR]

Background: Early water intake has gained widespread attention considering enhanced recovery after surgery (ERAS). In the present systematic evaluation and meta-analysis, we assessed the effects of early water intake on the incidence of vomiting and aspiration in adult patients who received general anaesthesia on regaining consciousness during the resuscitation period. Objective: To systematically analyse the results of randomised controlled trials on early postoperative water intake in patients who underwent different types of surgery under general anaesthesia, both at home and abroad, to further explore the safety and application of early water intake and provide an evidence-based foundation for clinical application. Design: Systematic review and meta-analysis. Methods: To perform the systematic evaluation and meta-analysis, we searched the Web of Science, CINAHL, Embase, PubMed, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI), Wanfang, and Vipshop databases to identify randomised controlled trial studies on early water intake in adult patients who received general anaesthesia. Results: Herein, we included 10 publications with a total sample size of 5131 patients. Based on statistical analysis, there was no statistically significant difference in the incidence of vomiting (odds ratio [OR] = 0.81; 95% confidence interval [CI] [0.58–1.12]; p = 0.20; I-squared [I2] = 0%) and aspiration (OR = 0.78; 95%CI [0.45–1.37]; p = 0.40; I2 = 0%) between the two groups of patients on regaining consciousness post-general anaesthesia. Conclusion: Based on the available evidence, early water intake after regaining consciousness post-anaesthesia did not increase the incidence of adverse complications when compared with traditional postoperative water abstinence. Early water intake could effectively improve patient thirst and facilitate the recovery of gastrointestinal function. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD). Methods: This study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups. Results: A total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031–362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259–92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005). Conclusion: NAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes. [ABSTRACT FROM AUTHOR]

Background: Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, however, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation. The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13. Methods: RT-qPCR was applied to measure the expression level of circ-ITCH and miR-17-5p in PC cell lines and tissues. CCK-8, colony formation, Brdu incorporation labeling and flow cytometry assays were applied to detect the effects of circ-ITCH and miR-17-5p on proliferation and cell apoptosis. Target gene prediction and screening, luciferase reporter gene assays were utilized to assess downstream target genes of miR-17-5p and Circ-ITCH. The protein and expression of HOXB13 gene were measured by Western blotting and RT-qPCR. Results: CircITCH was significantly reduced in PC cell lines and tissues. Low circITCH expression level was highly related with preoperative PSA, tumor stage and Gleason score. Overexpression of circITCH can inhibit the malignant phenotype of prostate cancer. There was a high negative relationship between the expression level of microRNA-17-5p and circITCH in PC tissues, however, there existed a positive relationship between the expression of HOXB13 and circITCH. CircITCH acted as a sponge of miR-17-5p to increase HOXB13 gene expression. In addition, miR-17-5p overexpression or HOXB13 silencing can reduce the carcinogenic effects of circICCH in prostate cancer. Conclusion: CircITCH promoted prostate cancer progression by regulating the HOXB13/miR-17-5p axis, and circITCH have a potential usage as therapeutic target for PC tumors. [ABSTRACT FROM AUTHOR]

Background: The ATLANTIC trial reported that higher PD-L1 expression in tumors was involved in a higher objective response in patients with EGFR+/ALK+ non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD-1/PD-L1 therapy as a third-line (or later) treatment for advanced NSCLC. Therefore, the determination of status and regulatory mechanisms of PD-L1 in EGFR mutant NSCLC before and after acquired EGFR-TKIs resistance are meaningful. Methods: The correlation among PD-L1, c-MET, and HGF was analyzed based on TCGA datasheets and paired NSCLC specimens before and after acquired EGFR-TKI resistance. EGFR-TKI resistant NSCLC cells with three well-known mechanisms, c-MET amplification, hepatocyte growth factor (HGF), and EGFR-T790M, were investigated to determinate PD-L1 expression status and immune escape ability. PD-L1-deleted EGFR-TKIs sensitive and resistant cells were used to evaluate the immune escape ability of tumors in mice xenograft models. Results: Positive correlations were found among PD-L1, c-MET, and HGF, based on TCGA datasheets and paired NSCLC specimens. Moreover, the above three resistant mechanisms increased PD-L1 expression and attenuated activation and cytotoxicity of lymphocytes in vitro and in vivo, and downregulation of PD-L1 partially restored the cytotoxicity of lymphocytes. Both MAPK and PI3K pathways were involved in the three types of resistance mechanism-induced PD-L1 overexpression, whereas the NF-kappa B pathway was only involved in T790M-induced PD-L1 expression. Conclusions: HGF, MET-amplification, and EGFR-T790M upregulate PD-L1 expression in NSCLC and promote the immune escape of tumor cells through different mechanisms. [ABSTRACT FROM AUTHOR]

Background: Ischemic events are the most common postoperative complication in bypass surgery for moyamoya disease (MMD), but the risk factors for pediatric MMD remain unclear. The goal of the study was to investigate the risk factors for postoperative ischemic complications in pediatric MMD patients.Methods: We retrospectively reviewed a consecutive series of pediatric MMD cases at Beijing Tiantan Hospital, Capital Medical University from June 2010 through June 2019. Preoperative clinical variables and radiographic findings were recorded, and logistic regression analysis was carried out to identify the risk factors for postoperative ischemic events.Results: A total of 533 operations in 336 patients were included in this study. Postoperative complications occurred after 51 operations (9.6%), including 40/447 indirect bypass procedures, 9/70 direct bypass procedures, and 2/16 combined bypass procedures. Postoperative ischemic events were the most common complication and occurred in 30 patients after 31 procedures (8.9% per patient; 5.8% per operation), including 26/447 indirect bypass procedures, 4/70 direct bypass procedures, and 1/16 combined bypass procedures, and the incidence of these events did not differ significantly between indirect and non-indirect bypass (5.8% vs 5.8%; p = 0.999). Multivariate logistic regression analyses revealed that older age at operation (OR 1.129, 95% CI 1.011-1.260, p = 0.032) and posterior cerebral artery involvement (OR 2.587, 95% CI 1.030-6.496, p = 0.043) were significantly associated with postoperative ischemic events.Conclusion: We speculate that older age at operation and posterior cerebral artery involvement are risk factors for postoperative ischemic events in pediatric MMD patients. [ABSTRACT FROM AUTHOR]

Background: Catheter Associated Urinary Tract Infections are among the most common urological infections world-wide. Bacterial biofilms and encrustation cause significant complications in patients with urinary catheters. The objective of the study is to demonstrate the efficacy and safety of an anti-microbial and anti-encrustation silver nanoparticle (AgNP) coating on silicone urinary catheter in two different animal models.Methods: Antifouling coating (P3) was prepared with alternate layers of polydopamine and AgNP and an outermost antifouling layer. Sixteen C57BL/6 female mice and two female PWG Micropigs® were used to perform the experiments. In mice, a 5 mm long silicone catheter with or without P3 was transurethrally placed into the urinary bladder. Micropigs were transurethrally implanted - one with P3 silicone catheter and the other with commercially available silver coated silicone catheter. Both models were challenged with E. coli. Bacteriuria was evaluated routinely and upon end of study (2 weeks for mice, 3 weeks for micropigs), blood, catheters and bladders were harvested and analysed for bacterial colonization and encrustation as well as for toxicity.Results: Lower bacterial colonization was seen on P3 catheters as well as in bladders of animals with P3 catheter. Bacteriuria was consistently less in mice with P3 catheter than with uncoated catheters. Encrustation was lower on P3 catheter and in bladder of micropig with P3 catheter. No significant toxicity of P3 was observed in mice or in micropig as compared to controls. The numbers were small in this proof of concept study and technical issues were noted especially with the porcine model.Conclusions: Antifouling P3 coating reduces bacterial colonization on catheter and in animal bladders without causing any considerable toxicity for 2 to 3 weeks. This novel coating could potentially reduce the complications of indwelling urethral catheters. [ABSTRACT FROM AUTHOR]

Background: As one of the most common chronic diseases in the world, osteoporosis occurs especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as major drivers in human disease. The aim of the present study was to analyse circRNA expression profiles in osteoporosis and to explore the clinical significance and the regulatory molecular mechanism of hsa_circ_0006859 during osteoporosis. Methods: Exosomes were isolated from clinically collected serum samples. A circRNA microarray was performed to screen differentially expressed circRNAs. Quantitative real-time PCR (qRT-PCR) and western blot were performed to analyse target gene mRNA expression and protein expression. Alizarin red staining (ARS) was performed to evaluate the mineralization ability of human bone marrow mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to evaluate the lipid droplet formation ability of hBMSCs. Bioinformatics analysis and the luciferase reporter assay were performed to investigate the interaction between two genes. Results: Hsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosomes was upregulated in osteoporosis patients compared to healthy controls. Hsa_circ_0006859 differentiated osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Hsa_circ_0006859 suppressed osteoblastic differentiation and promoted adipogenic differentiation of hBMSCs. Hsa_circ_0006859 directly bound to miR-431-5p, and ROCK1 was identified as a novel target gene of miR-431-5p. Hsa_circ_0006859 is a competing endogenous RNA (ceRNA) of miR-431-5p that promotes ROCK1 expression. Hsa_circ_0006859 suppressed osteogenesis and promoted adipogenesis by sponging miR-431-5p to upregulate ROCK1. Conclusions: Exosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis and controls the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-431-5p. [ABSTRACT FROM AUTHOR]

Background: Short-term exposure to air pollution may trigger symptoms of drug-resistant tuberculosis (DR-TB) through stimulating lung tissue, damaging tracheobronchial mucosa, the key anti-mycobacterium T cell immune function, and production and release of inflammatory cytokines. Objective: To investigate the association between acute exacerbations of DR-TB and short-term residential exposure to air pollutants (PM10, PM2.5, SO2, NO2, CO and O3) based on a large prospective cohort in Anhui Province, China. Method: Patients were derived from a prospective cohort study of DR-TB in Anhui Province. All DR-TB patients underwent drug-susceptibility testing and prefecture-level reference laboratories confirmed their microbiologies. The case-crossover design was performed to evaluate the association between the risk of acute exacerbations of DR-TB and short-term residential exposure to air pollution. Results: Short-term NO2 exposure was significantly related to an elevated risk of first-time outpatient visit due to acute exacerbations of DR-TB(relative risk:1.159, 95% confidence interval:1.011 ~ 1.329). Stratification analyses revealed that the relationship between the risk of acute exacerbations and NO2 exposure was stronger in the elderly (age ≥ 65) DR-TB patients, and in individuals with a history of TB treatment. Conclusions: NO2 Exposure was significantly associated with an elevated risk of acute exacerbation of DR-TB in Anhui Province, China. [ABSTRACT FROM AUTHOR]

Background: Rats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS.Methods: We created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry.Results: Hyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus- or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors.Conclusions: p66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions. [ABSTRACT FROM AUTHOR]

Multiple mechanisms are involved in kidney damage, among which the role of epigenetic modifications in the occurrence and development of kidney diseases is constantly being revealed. However, N6-methyladenosine (M6A), a well-known post-transcriptional modification, has been regarded as the most prevalent epigenetic modifications in higher eukaryotic, which is involved in various biological processes of cells such as maintaining the stability of mRNA. The role of M6A modification in the mechanism of kidney damage has attracted widespread attention. In this review, we mainly summarize the role of M6A modification in the progression of kidney diseases from the following aspects: the regulatory pattern of N6-methyladenosine, the critical roles of N6-methyladenosine in chronic kidney disease, acute kidney injury and renal cell carcinoma, and then reveal its potential significance in the diagnosis and treatment of various kidney diseases. A better understanding of this field will be helpful for future research and clinical treatment of kidney diseases. [ABSTRACT FROM AUTHOR]

Background: Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials. Methods: Female Sprague–Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining. Results: Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen. Conclusion: Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis. [ABSTRACT FROM AUTHOR]

Background: Rabbits are well-domesticated animals. As a crucial economic animal, rabbit has been successfully bred into wool-use, meat-use and fur-use breeds. Hair length is one of the most economically important traits affecting profitability in wool rabbits. In this study, to identify selection signatures with the long-hair trait, whole-genomic resequencing of long-haired rabbits (Angora rabbits) and short-haired rabbits (Rex and New Zealand rabbits) was performed. Results: By genome-wide selective sweeping analysis based on population comparison, we identified a total of 5.85 Mb regions (containing 174 candidate genes) with strong selection signals. Six of these genes (Dusp1, Ihh, Fam134a, Map3k1, Spata16, and Fgf5) were enriched in the MAPK signalling and Hedgehog signalling pathways, both of which are closely associated with hair growth regulation. Among these genes, Fgf5 encodes the FGF5 protein, which is a well-established regulator of hair growth. There was a nonsynonymous nucleotide substitution (T19234C) in the Fgf5 gene. At this locus, the C allele was present in all of the tested Angora rabbits, while the T allele was dominant in New Zealand and Rex rabbits. We further confirmed that the C allele was conserved in Angora rabbits by screening an additional 135 rabbits. Moreover, the results of functional predictions and co-immunoprecipitation revealed that the T19234C mutation impaired the binding capacity of FGF5 to its receptor FGFR1. Conclusions: We discovered that the homozygous missense mutation T19234C within Fgf5 might contribute to the long-hair trait of Angora rabbits by reducing its receptor binding capacity. This finding will provide new insights into the genetic basis underlying the genetic improvement of Angora rabbits and benefit the improvement of rabbit breeding in the future. [ABSTRACT FROM AUTHOR]

Background: Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq. Methods: A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed. Results: The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence. Conclusions: The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer" published in Experimental Hematology & Oncology. The correction addresses an error in Fig. 3E, F of the article, where the authors mistakenly used the wrong picture. The correct figure is provided in the correction notice. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Background: Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China.Methods: In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the Tellgenplex™ HPV DNA Assay.Results: The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a "two-peak" pattern, with the youngest age group (15-19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50-60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections.Conclusions: This study shows that HPV infection in China has increased to the level of an "HPV-heavy-burden" zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs. [ABSTRACT FROM AUTHOR]

6 hsa circ 0006859 suppresses osteogenesis and promotes adipogenesis by sponging miR-431-5p to upregulate ROCK1. a Relative miR-431-5p expression in hBMSCs after transfection with miR-431 M or miR-431I. b ALP activity in hBMSCs after transfection with miR-431 M or miR-431I. c Alizarin red staining was used to detect the mineralization ability of hBMSCs after transfection with miR-431 M or miR-431I. d Oil Red O staining of hBMSCs after transfection with miR-431 M or miR-431I. e Relative ROCK1 mRNA expression in hBMSCs after transfection with OE-ROCK1, si-ROCK1 #1, si-ROCK1 #2, or si-ROCK1 #3. f Western blot analysis of ROCK1 expression in hBMSCs after transfection with OE-ROCK1, si-ROCK1 #1, si-ROCK1 #2, or si-ROCK1 #3. g Alizarin red staining of hBMSCs after transfection with OE-ROCK1 or si-ROCK1. h Oil Red O staining of hBMSCs after transfection with OE-ROCK1 or si-ROCK1. i Alizarin red staining of hBMSCs after transfection with si-NC+EV, si-NC+OE-circ, si-ROCK1+EV, or si-ROCK1+OE-circ. j Oil Red O staining of hBMSCs after transfection with si-NC+EV, si-NC+OE-circ, si-ROCK1+EV, or si-ROCK1+OE-circ Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Correction: Exosomal hsa circ 0006859 is a potential biomarker for postmenopausal osteoporosis and enhances adipogenic versus osteogenic differentiation in human bone marrow mesenchymal stem cells by sponging miR-431-5p Feng Zhi and Yi Ding contributed equally to this work Correction: Stem Cell Res Ther 12, 157 (2021) https://doi.org/10.1186/s13287-021-02214-y Following publication of the original article [[1]], the authors identified that there are image overlap in the Alizarin red staining experiment in Fig. [Extracted from the article]

Purpose: To analyse and summarize branching pattern types of the interlobar portion of right pulmonary arteries (RPA) through chest thin-slice CT scans and three-dimensional reconstruction. Methods: A total of 179 patients (58 males and 121 females, with an average age of 53.9 years) at the Thoracic Surgery Department of Ningbo First Hospital were retrospectively included from December 2020 to December 2021. All patients completed preoperative thin-slice CT scans and three-dimensional reconstructions of the chest. The clinical data and branching patterns were collected. Data were analysed using SPSS 21.0. Results: The branching pattern types of the interlobar portion of RPA were divided into 4 types according to the order and number of branches: Type I (145/179, 81.0%), Asc. A2, MA, A6; Type II (28/179, 15.6%), Asc. A2 deletion, MA, A6; Type III (5/179, 2.8%), Asc. A2, A6, MA; and Type IV (1/179, 0.6%), MA, Asc. A2, A6. Type I was the most common pattern. Furthermore, according to the number of branches of MA and A6, this pattern can be subdivided into 15 subcategories. Conclusion: Chest thin-slice CT scans and 3D reconstructions can provide surgeons with accurate lung anatomy, which helps surgeons perform preoperative planning and complete surgery successfully. [ABSTRACT FROM AUTHOR]

Background and aims: Effective traction is an important prerequisite for successful endoscopic submucosal dissection (ESD). The combined orthodontic rubber band (ORB) and clip method was effective in colorectal cancer ESD. To date, the method was not reported in gastric ESD. This study aimed to investigate its efficacy and safety for gastric neoplasms ESD. Methods: We retrospectively analyzed data of 118 patients with gastric neoplasms treated by ESD from November 2020 to April 2022, 43 by ORB-ESD and 75 by the conventional ESD. The primary outcome measure was the ESD procedure time. Clinical data on efficacy and safety were also collected and analyzed. Propensity score matching (PSM) matched the patients in both groups. Results: PSM successfully matched 31 pairs of patients. The ORB-ESD operation time was shorter (median [interquartile range], 35 [30–48] vs. 49 [40–70] min, P < 0.001) and dissection speed was higher (median [interquartile range], 22.6 [14.4–29.3] vs. 13.5 [9.6–17.9] mm2/min, P < 0.001) than in the conventional ESD. The groups were similar in muscular injury rate, frequency and time of use of thermal hemostatic forceps, postoperative adverse events, en bloc resection, and R0 resection rate (P > 0.05). Conclusions: Compared to the conventional ESD, ORB-ESD significantly reduced the procedure time and increased the dissection speed, proving beneficial to gastric ESD. [ABSTRACT FROM AUTHOR]

Dysregulated mucosal immune responses and colonic fibrosis impose two formidable challenges for ulcerative colitis treatment. It indicates that monotherapy could not sufficiently deal with this complicated disease and combination therapy may provide a potential solution. A chitosan-modified poly(lactic-co-glycolic acid) nanoparticle (CS-PLGA NP) system was developed for co-delivering patchouli alcohol and simvastatin to the inflamed colonic epithelium to alleviate the symptoms of ulcerative colitis via remodeling immune microenvironment and anti-fibrosis, a so-called "two-birds-one-stone" nanotherapeutic strategy. The bioadhesive nanomedicine enhanced the intestinal epithelial cell uptake efficiency and improved the drug stability in the gastrointestinal tract. The nanomedicine effectively regulated the Akt/MAPK/NF-κB pathway and reshaped the immune microenvironment through repolarizing M2Φ, promoting regulatory T cells and G-MDSC, suppressing neutrophil and inflammatory monocyte infiltration, as well as inhibiting dendritic cell maturation. Additionally, the nanomedicine alleviated colonic fibrosis. Our work elucidates that the colon-targeted codelivery for combination therapy is promising for ulcerative colitis treatment and to address the unmet medical need. [ABSTRACT FROM AUTHOR]

Dysregulated mucosal immune responses and colonic fibrosis impose two formidable challenges for ulcerative colitis treatment. It indicates that monotherapy could not sufficiently deal with this complicated disease and combination therapy may provide a potential solution. A chitosan-modified poly(lactic-co-glycolic acid) nanoparticle (CS-PLGA NP) system was developed for co-delivering patchouli alcohol and simvastatin to the inflamed colonic epithelium to alleviate the symptoms of ulcerative colitis via remodeling immune microenvironment and anti-fibrosis, a so-called "two-birds-one-stone" nanotherapeutic strategy. The bioadhesive nanomedicine enhanced the intestinal epithelial cell uptake efficiency and improved the drug stability in the gastrointestinal tract. The nanomedicine effectively regulated the Akt/MAPK/NF-κB pathway and reshaped the immune microenvironment through repolarizing M2Φ, promoting regulatory T cells and G-MDSC, suppressing neutrophil and inflammatory monocyte infiltration, as well as inhibiting dendritic cell maturation. Additionally, the nanomedicine alleviated colonic fibrosis. Our work elucidates that the colon-targeted codelivery for combination therapy is promising for ulcerative colitis treatment and to address the unmet medical need. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism has been a major public health problem and caused a heavy disease burden. Venous thromboembolism clinical decision support system was proved to have a positive influence on the prevention and management of venous thromboembolism. As the direct users, nurses' acceptance of this system is of great importance to support the successful implementation of it. However, there are few relevant studies to investigate nurses' acceptance and the associated factors are still unclear.Objective: To investigate the determinant factors of nurses' acceptance of venous thromboembolism clinical decision support system with the modified Unified Theory of Acceptance and Use of Technology.Methods: We designed a questionnaire based on the modified Unified Theory of Acceptance and Use of Technology and then a cross-sectional survey was conducted among nurses in a tertiary hospital in Nanjing, China. Statistically, a Structural Equation Modeling -Partial Least Squares path modeling approach was applied to examine the research model.Results: A total of 1100 valid questionnaires were recycled. The modified model explained 74.7%, 83.0% and 86% of the variance in user satisfaction, behavioral intention and user behavior, respectively. The results showed that performance expectancy (β = 0.254, p = 0.000), social influence (β = 0.136, p = 0.047), facilitating conditions (β = 0.245, p = 0.000), self-efficacy (β = 0.121, p = 0.048) and user satisfaction (β = 0.193, p = 0.001) all had significant effects on nurses' intention. Although effort expectancy (β = 0.010, p = 0.785) did not have a direct effect on nurses' intention, it could indirectly influence nurses' intention with user satisfaction as the mediator (β = 0.296, p = 0.000). User behavior was significantly predicted by facilitating conditions (β = 0.298, p = 0.000) and user intention (β = 0.654, p = 0.001).Conclusion: The research enhances our understanding of the determinants of nurses' acceptance of venous thromboembolism clinical decision support system. Among these factors, performance expectancy was considered as the top priority. It highlights the importance of optimizing system performance to fit the users' needs. Generally, the findings in our research provide clinical technology designers and administrators with valuable information to better meet users' requirements and promote the implementation of venous thromboembolism clinical decision support system. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus is a global health problem. It often leads to a decline in the differentiation capacity of myoblasts and progressive loss of muscle mass, which in turn results in deterioration of skeletal muscle function. However, effective therapies against skeletal muscle diseases are unavailable. Methods: Skeletal muscle mass and differentiation ability were determined in db/+ and db/db mice. Transcriptomics and metabolomics approaches were used to explore the genetic mechanism regulating myoblast differentiation in C2C12 myoblasts. Results: In this study, the relatively uncharacterized solute carrier family gene Slc2a6 was found significantly up-regulated during myogenic differentiation and down-regulated during diabetes-induced muscle atrophy. Moreover, RNAi of Slc2a6 impaired the differentiation and myotube formation of C2C12 myoblasts. Both metabolomics and RNA-seq analyses showed that the significantly differentially expressed genes (e.g., LDHB) and metabolites (e.g., Lactate) during the myogenic differentiation of C2C12 myoblasts post-Slc2a6-RNAi were enriched in the glycolysis pathway. Furthermore, we show that Slc2a6 regulates the myogenic differentiation of C2C12 myoblasts partly through the glycolysis pathway by targeting LDHB, which affects lactic acid accumulation. Conclusion: Our study broadens the understanding of myogenic differentiation and offers the Slc2a6-LDHB axis as a potential therapeutic target for the treatment of diabetes-associated muscle atrophy. 9EwrcanKTNC1Ad2TsfVLd8 Video abstract [ABSTRACT FROM AUTHOR]

Background: Aberrant methylation of EphA7 has been reported in the process of carcinogenesis but not in cervical cancer. Therefore, an integration study was performed to explore the association between EphA7 hypermethylation and cervical cancer and validate the potential value of EphA7 hypermethylation in the diagnosis of cervical cancer.Methods: We performed an integration study to identify and validate the association between EphA7 methylation and cervical cancer. First, data on EphA7 methylation and expression in cervical cancer were extracted and analyzed via bioinformatics tools. Subsequently, CRISPR-based methylation perturbation tools (dCas9-Tet1/DNMT3a) were constructed to further demonstrate the association between DNA methylation and EphA7 expression. Ultimately, the clinical value of EphA7 methylation in cervical cancer was validated in cervical tissues and Thinprep cytologic test (TCT) samples by methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP), respectively.Results: Pooled analysis showed that EphA7 promoter methylation levels were significantly increased in cervical cancer compared to normal tissues (P < 0.001) and negatively correlated with EphA7 expression. These prediction results were subsequently confirmed in cell lines; moreover, CRISPR-based methylation perturbation tools (dCas9-Tet1/DNMT3a) demonstrated that DNA methylation participates in the regulation of EphA7 expression directly. Consistent with these findings, the methylation level and the positive rate of EphA7 gradually increased with severity from normal to cancer stages in TCT samples (P < 0.01).Conclusions: EphA7 hypermethylation is present in cervical cancer and is a potential biomarker for the diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Prenatal anxiety is a common concern which may have adverse effects on maternal and infant health outcomes. Studies addressing needs-based education interventions for prenatal anxiety are limited.Aim: To explore the effects of needs-based education on alleviating prenatal anxiety among advanced multiparas when compared with routine prenatal health education.Methods: A total of 86 advanced multiparas were randomized into the intervention group (n = 43) or the control group (n = 43) in this study. The control group received routine prenatal care. The intervention group received five needs-based education programs presented by trained researchers. The Pregnancy-related Anxiety Questionnaire was used to evaluate changes in anxiety level of participants. Concurrent physiological parameters, including blood pressure, heart rate and non-stress test were also measured.Results: Scores on the Pregnancy-related Anxiety Questionnaire of the intervention group were significantly lower than those of the control group (t = 4.21, P < 0.05). Systolic blood pressure (t = 3.64, P < 0.05) and heart rate (t = 2.39, P < 0.05) of the intervention group were also significantly lower than the control group whereas no differences were noted in diastolic blood pressure and non-stress test.Conclusion: A needs-based education program is an effective intervention strategy to allay prenatal anxiety in advanced multiparas.Trial Registration: The trial was retrospectively registered in the Chinese Clinical Trial Registry as number ChiCTR2100047552 . [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of different adjuvant therapy on IB1 and IIA1 stage cervical squamous cell cancer patients with lymphovascular space invasion. It also aimed to analyze the relationship between lymphovascular space invasion and other clinical pathological characteristics on IB1 and IIA1 stage cervical squamous cell cancer patients.Methods: This retrospective observational study collected data of FIGO stages IB1 and IIA1 squamous cervical cancer patients at the First Affiliated Hospital of Chongqing Medical University between 2014 and 2018. A correlation analysis between lymphovascular space invasion and other clinical or pathological factors was conducted. Prognosis analysis of patients with lymphovascular space invasion were performed to assess associations between clinical-pathological characteristics and survival.Results: A total of 357 women were identified including 110 (30.8%) with lymphovascular space invasion, 247 (69.2%) without lymphovascular space invasion. Both middle 1/3 cervical stromal invasion (p = 0.000) and deep 1/3 cervical stromal invasion (p = 0.000) were independently associated with lymphovascular space invasion. Among lymphovascular space involved women, tumor differentiation (P = 0.001) and postoperative therapy (P = 0.036) had a significant influence on disease recurrence. Multivariate analysis showed that lymph node metastasis (P = 0.017), poorer tumor differentiation (P = 0.036) and postoperative chemotherapy alone (P = 0.021) can increase the risk of tumor relapse.Conclusion: Our study suggested that the presence of deep stromal invasion independently increases the risk of lymphovascular space invasion. Compared with chemotherapy, chemoradiotherapy seems to improve progression-free survival in squamous cervical cancer patients with lymphovascular space invasion. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, differentially expressed proteins were identified. Methods: Human peripheral blood mononuclear cells were stimulated with macrophage colony-stimulating factor, and obtained macrophages were transformed into foam cells by oxidized low-density lipoprotein. Tandem mass tag (TMT) labeling combined with mass spectrometry was performed to find associations between foam cell transformation and proteome profiles. Results: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus, whereas upregulated DEPs of foam cells/macrophages were mostly extracellular or located in the plasma membrane. Functional analysis of DEPs demonstrated that cholesterol metabolism-related proteins were upregulated in foam cells, whereas immune response-related proteins were downregulated in foam cells. The protein interaction network showed that the DEPs with the highest interaction scores between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions: Proteomics analysis suggested that cholesterol metabolism was upregulated, while the immune response was suppressed in foam cells. KEGG enrichment analysis and protein-protein interaction analysis indicated that DEPs located in the endoplasmic reticulum and lysosomes might be key drivers of foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism underlying macrophage transformation to foam cells. [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease which leads to progressive stenosis and occlusion of the bilateral internal carotid artery and main intracerebral arteries. Concerns are always on how the hemisphere with infarction affects cognitive function, while little attention is paid to the role that the non-infarcted hemisphere plays. Therefore, we aimed to detect cortical indexes, especially cortical complexity in the left or right hemisphere separately in patients with MMD after stroke.Methods: 28 patients with MMD (14 males, 14 females) and 14 healthy controls were included in this study. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scan. The preprocessing of three-dimensional T1 weighted images were performed by standard surface-based morphometry. Surface-based morphometry statistical analysis was carried out with a threshold of False Discovery Rate (FDR) P < 0.05 and fractal dimension (FD) was used to provide a quantitative description of cerebral cortical complexity.Results: Widespread cognitive dysfunctions were found in MMD patient with stroke. Extensive FD reduction in the left hemisphere with right-sided infarction, mainly in the superior temporal, inferior frontal, and insula, while the post central gyrus, superior parietal, and inferior parietal gyrus also showed a wide range of significant differences (FDR corrected P < 0.05). Meanwhile, FD changes in the right hemisphere with left-sided infarction are restricted to the precuneus and cingulate isthmus (FDR corrected P < 0.05).Conclusions: Extensive cognitive impairment was reconfirmed in Moyamoya disease with stroke, while wild and asymmetrical decrease of cortical complexity is observed on both sides. These differences could be relative to unbalanced cognitive dysfunction, and may be the result of a long-term chronic ischemia and compensatory of the contralateral hemisphere to the infarction. [ABSTRACT FROM AUTHOR]

In addition to early detection, early diagnosis, and early surgery, it is of great significance to use new strategies for the treatment of hepatocellular carcinoma (HCC). Studies showed that the combination of sorafenib (SFN) and triptolide (TPL) could reduce the clinical dose of SFN and maintain good anti-HCC effect. But the solubility of SFN and TPL in water is low and both drugs have certain toxicity. Therefore, we constructed a biomimetic nanosystem based on cancer cell-platelet (PLT) hybrid membrane camouflage to co-deliver SFN and TPL taking advantage of PLT membrane with long circulation functions and tumor cell membrane with homologous targeting. The biomimetic nanosystem, SFN and TPL loaded cancer cell-PLT hybrid membrane-camouflaged liquid crystalline lipid nanoparticles ((SFN + TPL)@CPLCNPs), could simultaneously load SFN and TPL at the molar ratio of SFN to TPL close to 10:1. (SFN + TPL)@CPLCNPs achieved long circulation function and tumor targeting at the same time, promoting tumor cell apoptosis, inhibiting tumor growth, and achieving a better "synergy and attenuation effect", which provided new ideas for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women. Insulin resistance (IR) has emerged as a central contributor to the pathogenesis of this disease. According to traditional Chinese medicine (TCM), kidney deficiency is the main syndrome of PCOS. The deficiency of the kidney cannot vaporize water-dampness, and the retention of water-dampness accumulates into phlegm dampness stagnation, resulting in visceral dysfunction and metabolic disorder. TCM involving syndrome differentiation and treatment is widely used to adjust women's menstrual cycles. Our patented formula Bushen Huatan Decoction (BSHTD) has been proven to be effective in the clinical treatment of IR-PCOS. Baduanjin also plays an important role in improving metabolic syndrome through lifestyle intervention. This study investigates the clinical efficacy of Bushen Huatan Decoction combined with Baduanjin in IR-PCOS, to form a specific TCM-behaviour intervention plan in the treatment of IR-PCOS.Methods/design: This is a randomized controlled trial involving 190 participants diagnosed with IR-PCOS. All participants will be randomly allocated into 5 groups: group A will receive metformin; group B, BSHTD; group C, Baduanjin; group D, BSHTD combined with metformin; and group E, BSHTD combined with Baduanjin. One course of treatment lasts 3 months, a total of two courses. The primary outcomes are changes in the homeostatic model assessment of insulin resistance (HOMA-IR) and improvements in the oral glucose tolerance test (OGTT) and insulin-releasing test (INS). The secondary outcomes are improvements in the menstrual cycle, ovulation rate, clinical pregnancy rate, basic serum sex hormone levels, free androgen index (FAI), Ferriman-Gallwey scores, body mass index (BMI) and TCM syndrome scores. The related observation indexes will be collected at baseline, during the process of treatment and at the 6-month follow-up. Simultaneously, close monitoring of possible adverse events will be performed throughout the trial process.Discussion: This trial will investigate the efficacy of the comprehensive intervention program of Bushen Huatan Decoction combined with Baduanjin on the adjustment of the menstrual cycle, improvement of insulin resistance and correction of glucose metabolism disorder in IR-PCOS patients. It is expected to form an alternative treatment of TCM-behaviour intervention therapy for IR-PCOS and promote the Chinese fitness Qigong Baduanjin in the application of lifestyle diseases.Trial Registration: Chinese Clinical Trial Registry ChiCTR2100043415 . Registered on 15 February 2021. [ABSTRACT FROM AUTHOR]

Background: Second head and neck neuroendocrine carcinoma (NEC) after radical radiotherapy for nasopharyngeal carcinoma (NPC) treatment is rarely reported. The prognosis of second cancer is poor, and our research focuses on finding a breakthrough in the treatment. In this study, we aimed to investigate clinicopathological characteristics and to identify the genomic landscape of second head and neck NECs.Methods: We collected five second head and neck NEC cases in the recent three years from our patient database. Clinicopathological data and images were obtained. Genomic analysis was performed using high-throughput second generation sequencing. KEGG pathway enrichment analyses between high-frequency mutations were performed using the STRING database.Results: All patients had been diagnosed with second NEC, according to the pathological observations. The interval between diagnosis of NPC and NEC ranged from 10 to 18 years. Two patients had brain or liver metastasis at three and nine months, respectively, after the diagnosis of NEC. Three patients died of the disease with the overall survival time ranging from three to nine months. Commonly altered genes (50%) in second head and neck NECs included TP53, RB1, NOTCH2, PTEN, POLG, KMT2C, U2AF1, EPPK1, ELAC2, DAXX, COL22A1, and ABL1. Those genetic lesions might affect p53 signaling, MAPK signaling, PI3K-Akt signaling, sphingolipid signaling, and neurotrophin signaling pathways.Conclusions: Second head and neck NECs had poor prognosis. We revealed, for the first time, the mutational landscape, high-frequency somatic mutations, and potential signaling pathways of second head and neck NECs. Its optimal treatment model needs to be further studied in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic carotid artery stenosis (aCAS) impairs haemodynamic and cognitive functions; however, the relationship between these changes and brain network connectivity remains largely unknown. This study aimed to determine the relationship between functional connectivity and neurocognition in patients with aCAS.Methods: We compared functional status in 14 patients with aCAS and 15 healthy controls using resting state functional magnetic resonance imaging sequences. The subjects underwent a full range of neuropsychological tests and a graphical theoretical analysis of their brain networks.Results: Compared with controls, patients with aCAS showed significant decline in neuropsychological functions, particularly short-term memory (word-memory, p = .046 and picture-memory, p = .014). Brain network connectivity was lower in patients with aCAS than in the controls, and the decline of functional connectivity in aCAS patients was mainly concentrated in the left and right inferior frontal gyri, temporal lobe, left cingulate gyrus, and hippocampus. Decreased connectivity between various brain regions was significantly correlated with impaired short-term memory. Patients with aCAS showed cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. The cognitive defects were mainly manifested in the short-term memory of words and pictures.Conclusions: This study is the first of its kind to identify an association between disruption of functional connections in left carotid stenosis and impairment of short-term memory. The findings suggest that alterations in network connectivity may be an essential mechanism underlying cognitive decline in aCAS patients.Clinical Trial Registration-url: Unique identifier: 04/06/2019, ChiCTR1900023610 . [ABSTRACT FROM AUTHOR]

Background: To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. Methods: Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. Results: Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). Conclusions: For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. Trial registration: This project has been registered in the Chinese Clinical Trial Registry (ChiCTR1800019978). [ABSTRACT FROM AUTHOR]

Background: The association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer.Methods: First, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROCAUC.Results: Pooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37.Conclusion: SOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Moyamoya disease (MMD) impairs hemodynamic and cognitive function. The relationship between these changes, cerebral blood flow (CBF), and network connectivity remains largely unknown. The aim of this study was to increase understanding of the relationship between CBF, functional networks, and neurocognition in adults with asymptomatic MMD. We compared CBF and functional status in 26 patients with MMD and 20 healthy controls using arterial spin labeling and resting state functional magnetic resonance imaging sequences. At the same time, a detailed cognitive test was performed in 15 patients with no cerebral or lumen infarction who were selected by magnetic resonance imaging-T2 FLAIR screening.Results: Compared to the controls, the patients showed varying degrees of decline in their computational ability (simple subtraction, p = 0.009; complex subtraction, p = 0.006) and short-term memory (p = 0.042). The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island flap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group.Conclusions: In patients with asymptomatic MMD, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline and appear before clinical symptoms. Clinical trial registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR1900023610. [ABSTRACT FROM AUTHOR]

The combination of an immuno-metabolic adjuvant and immune checkpoint inhibitors holds great promise for effective suppression of tumor growth and invasion. In this study, a pH-responsive co-delivery platform was developed for metformin (Met), a known immuno-metabolic modulator, and short interfering RNA (siRNA) targeting fibrinogen-like protein 1 mRNA (siFGL1), using a hybrid biomimetic membrane (from macrophages and cancer cells)-camouflaged poly (lactic-co-glycolic acid) nanoparticles. To improve the endo-lysosomal escape of siRNA for effective cytosolic siRNA delivery, a pH-triggered CO2 gas-generating nanoplatform was developed using the guanidine group of Met. It can react reversibly with CO2 to form Met-CO2 for the pH-dependent capture/release of CO2. The introduction of Met, a conventional anti-diabetic drug, promotes programmed death-ligand 1 (PD-L1) degradation by activating adenosine monophosphate-activated protein kinase, subsequently blocking the inhibitory signals of PD-L1. As a result, siFGL1 delivery by the camouflaged nanoparticles of the hybrid biomimetic membrane can effectively silence the FGL1 gene, promoting T-cell-mediated immune responses and enhancing antitumor immunity. We found that a combination of PD-L1/programmed death 1 signaling blockade and FGL1 gene silencing exhibited high synergistic therapeutic efficacy against breast cancer in vitro and in vivo. Additionally, Met alleviated tumor hypoxia by reducing oxygen consumption and inducing M1-type differentiation of tumor-related macrophages, which improved the tumor immunosuppressive microenvironment. Our results indicate the potential of hybrid biomimetic membrane-camouflaged nanoparticles and combined Met-FGL1 blockade in breast cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods: SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results: SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions: This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC. [ABSTRACT FROM AUTHOR]

Background: Maintenance of centrosome number in cells is essential for accurate distribution of chromosomes at mitosis and is dependent on both proper centrosome duplication during interphase and their accurate distribution to daughter cells at cytokinesis. Two essential regulators of cell cycle progression are protein phosphatase 1 (PP1) and Aurora A kinase (AURKA), and their activities are each regulated by the PP1 regulatory subunit, protein phosphatase 1 regulatory subunit 2 (PPP1R2). We observed an increase in centrosome number after overexpression of these proteins in cells. Each of these proteins is found on the midbody in telophase and overexpression of PPP1R2 and its mutants increased cell ploidy and disrupted cytokinesis. This suggests that the increase in centrosome number we observed in PPP1R2 overexpressing cells was a consequence of errors in cell division. Furthermore, overexpression of PPP1R2 and its mutants increased midbody length and disrupted midbody architecture. Additionally, we show that overexpression of PPP1R2 alters activity of AURKA and PP1 and their phosphorylation state at the centrosome. Results: Overexpression of PPP1R2 caused an increase in the frequency of supernumerary centrosomes in cells corresponding to aberrant cytokinesis reflected by increased nuclear content and cellular ploidy. Furthermore, AURKA, PP1, phospho PPP1R2, and PPP1R2 were all localized to the midbody at telophase, and PP1 localization there was dependent on binding of PPP1R2 with PP1 and AURKA as well as its phosphorylation state. Additionally, overexpression of both PPP1R2 and its C-terminal AURKA binding site altered enzymatic activity of AURKA and PP1 at the centrosome and disrupted central spindle structure. Conclusions: Results from our study reveal the involvement of PPP1R2 in coordinating PP1 and AURKA activity during cytokinesis. Overexpression of PPP1R2 or its mutants disrupted the midbody at cytokinesis causing accumulation of centrosomes in cells. PPP1R2 recruited PP1 to the midbody and interference with its targeting resulted in elongated and severely disrupted central spindles supporting an important role for PPP1R2 in cytokinesis. [ABSTRACT FROM AUTHOR]

Background: The Lycoris genus includes many ornamentally and medicinally important species. Polyploidization and hybridization are considered modes of speciation in this genus, implying great genetic diversity. However, the lack of effective molecular markers has limited the genetic analysis of this genus. Results: In this study, mining of EST-SSR markers was performed using transcriptome sequences of L. aurea, and 839 primer pairs for non-redundant EST-SSRs were successfully designed. A subset of 60 pairs was randomly selected for validation, of which 44 pairs could amplify products of the expected size. Cross-species transferability of the 60 primer pairs among Lycoris species were assessed in L. radiata Hreb, L. sprengeri Comes ex Baker, L. chinensis Traub and L. anhuiensis, of which between 38 to 77% of the primers were able to amplify products in these Lycoris species. Furthermore, 20 and 10 amplification products were selected for sequencing verification in L. aurea and L. radiata respectively. All products were validated as expected SSRs. In addition, 15 SSRs, including 10 sequence-verified and 5 unverified SSRs were selected and used to evaluate the genetic diversity of seven L. radiata lines. Among these, there were three sterile lines, three fertile lines and one line represented by the offspring of one fertile line. Unweighted pair group method with arithmetic mean analysis (UPGMA) demonstrated that the outgroup, L. aurea was separated from L. radiata lines and that the seven L. radiata lines were clustered into two groups, consistent with their fertility. Interestingly, even a dendrogram with 34 individuals representing the seven L. radiata lines was almost consistent with fertility. Conclusions: This study supplies a pool of potential 839 non-redundant SSR markers for genetic analysis of Lycoris genus, that present high amplification rate, transferability and efficiency, which will facilitate genetic analysis and breeding program in Lycoris. [ABSTRACT FROM AUTHOR]

Cell membrane- covered drug-delivery nanoplatforms have been garnering attention because of their enhanced bio-interfacing capabilities that originate from source cells. In this top-down technique, nanoparticles (NPs) are covered by various membrane coatings, including membranes from specialized cells or hybrid membranes that combine the capacities of different types of cell membranes. Here, hybrid membrane-coated doxorubicin (Dox)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (DPLGA@[RAW-4T1] NPs) were fabricated by fusing membrane components derived from RAW264.7(RAW) and 4T1 cells (4T1). These NPs were used to treat lung metastases originating from breast cancer. This study indicates that the coupling of NPs with a hybrid membrane derived from macrophage and cancer cells has several advantages, such as the tendency to accumulate at sites of inflammation, ability to target specific metastasis, homogenous tumor targeting abilities in vitro, and markedly enhanced multi-target capability in a lung metastasis model in vivo. The DPLGA@[RAW-4T1] NPs exhibited excellent chemotherapeutic potential with approximately 88.9% anti-metastasis efficacy following treatment of breast cancer-derived lung metastases. These NPs were robust and displayed the multi-targeting abilities of hybrid membranes. This study provides a promising biomimetic nanoplatform for effective treatment of breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Monochamus alternatus Hope is one of the insect vectors of pinewood nematode (Bursaphelenchus xylophilus), which causes the destructive pine wilt disease. The microorganisms within the ecosystem, comprising plants, their environment, and insect vectors, form complex networks. This study presents a systematic analysis of the bacterial microbiota in the M. alternatus midgut and its habitat niche. Methods: Total DNA was extracted from 20 types of samples (with three replicates each) from M. alternatus and various tissues of healthy and infected P. massoniana (pines). 16S rDNA amplicon sequencing was conducted to determine the composition and diversity of the bacterial microbiota in each sample. Moreover, the relative abundances of bacteria in the midgut of M. alternatus larvae were verified by counting the colony-forming units. Results: Pinewood nematode infection increased the microbial diversity in pines. Bradyrhizobium, Burkholderia, Dyella, Mycobacterium, and Mucilaginibacter were the dominant bacterial genera in the soil and infected pines. These results indicate that the bacterial community in infected pines may be associated with the soil microbiota. Interestingly, the abundance of the genus Gryllotalpicola was highest in the bark of infected pines. The genus Cellulomonas was not found in the midgut of M. alternatus, but it peaked in the phloem of infected pines, followed by the phloem of heathy pines. Moreover, the genus Serratia was not only present in the habitat niche, but it was also enriched in the M. alternatus midgut. The colony-forming unit assays showed that the relative abundance of Serratia sp. peaked in the midgut of instar II larvae (81%). Conclusions: Overall, the results indicate that the bacterial microbiota in the soil and in infected pines are correlated. The Gryllotalpicola sp. and Cellulomonas sp. are potential microbial markers of pine wilt disease. Additionally, Serratia sp. could be an ideal agent for expressing insecticidal protein in the insect midgut by genetic engineering, which represents a new use of microbes to control M. alternatus. [ABSTRACT FROM AUTHOR]