Search

Background: Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects., Methods: Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats., Results: In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery., Conclusions: Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects., Competing Interests: Declarations. Ethics approval and consent to participate: Title of the approved project: Nerve defect animal model(SD rats). Name of the institutional approval committee: the Ethics Committee of the Chinese PLA General Hospital. Approval number: SQ2022437. Date of approval: 2022-04-03. (2)Title of the approved project: Preparation of acellular nerves(SD rats). Name of the institutional approval committee: the Ethics Committee of the Chinese PLA General Hospital. Approval number:2022-X18-37. Date of approval:2022-01-08. In this study, all animal experiments were carried out following the guidelines and regulations related to the care and use of laboratory animals presented by the animal ethics committee of the Chinese PLA General Hospital (Code No.2022-X18-37). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Calf muscular vein thrombosis (CMVT) is a type of distal deep vein thrombosis, which is common in geriatric hip fracture patients. However, studies focusing on whether the orthopedic operation has an impact on the prognosis of geriatric hip fracture patients with CMVT are very limited. Therefore, the aim of this study was to explore whether geriatric hip fractures with CMVT affect the mortality of patients within one year postoperatively. The difficulty of the operation, postoperative complications, the status of thrombosis, and function scores were also compared., Materials and Methods: Geriatric hip fracture patients who underwent surgery between January 2019 and January 2021 were included. Patients were divided into groups with and without CMVT by preoperative color Doppler ultrasound examination. Propensity score-matching (PSM) was performed in a ratio of 1:1 between the patient with and without CMVT groups. Baseline characteristics, laboratory results, perioperative indicators and prognosis of patients were collected retrospectively. Intraoperative and postoperative comparisons were conducted between patients with and without CMVT., Results: Two hundred and sixty geriatric hip fracture patients were included. Eighty-nine patients in each group were matched after PSM. There was no significant difference in mortality between the two groups at one-month, three-month, six-month, and one-year postoperatively. However, patients with CMVT had longer hospital stays, a higher incidence of postoperative complications, and a higher incidence of thrombosis progression than patients without CMVT in the follow-up., Conclusion: No significant difference in mortality within one year postoperatively was observed in Chinese geriatric hip fracture patients with or without CMVT formation. Strategies such as close monitoring the status of thrombosis, individualized care, and strengthening rehabilitation are recommended to reduce the risk of complications and optimize patient outcomes in this patient population., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300069411). Registered March 15, 2023, https://www.chictr.org.cn/showproj.html?proj=192079 ., Competing Interests: Declarations. Ethics approval and consent to participate: The present study was approved by the Ethical Review Committee of West China Hospital, Sichuan University. Informed consent procedures for this study have been waived due to the retrospective design. Also, it was registered in Chinese Clinical Trial Registry with registration number of ChiCTR2300069411 on 15/03/2023. All procedures were conducted according to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Bacterial pathogens frequently encounter host-derived metabolites during their colonization and invasion processes, which can serve as nutrients, antimicrobial agents, or signaling molecules for the pathogens. The essential nutrient choline (Cho) is widely known to be utilized by a diverse range of bacteria and may undergo conversion into the disease-associated metabolite trimethylamine (TMA). However, the impact of choline metabolism on bacterial physiology and virulence remains largely unexplored., Methods: Here, we employed an in vitro infection model to investigate the role of Cho in intracellular survival and virulence of Pseudomonas aeruginosa (P. aeruginosa). Additionally, a comprehensive RNA-seq based transcriptomic analysis and various phenotypic assays were performed to elucidate the impacts of Cho on P. aeruginosa., Results: We observed that the Cho metabolite glycine betaine (GB) effectively reduced intracellular levels of cyclic-di-GMP (c-di-GMP). Supplementation of Cho or GB in P. aeruginosa had thus affected c-di-GMP regulated phenotypes, such as pyoverdine production, biofilm formation, and mobility. Depletion of Cho metabolism through knockout of the betAB operon resulted in compromised intracellular survival of P. aeruginosa. Notably, the P. aeruginosa betAB mutant elicited a more robust protective inflammatory response compared to the wild-type strain., Conclusion: Our study showed that P. aeruginosa Cho metabolism not only interferes host nutritional immunity, but also directly affect multiple virulence phenotypes through modulation of c-di-GMP signaling., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Thrombocytopenia (TP) is a hematological manifestation of systemic lupus erythematosus (SLE) and is associated with unfavorable prognostic outcomes. This study aimed to develop a risk prediction model for new-onset TP in SLE patients., Methods: Based on the multicenter prospective Chinese SLE Treatment and Research Group (CSTAR) registry, newly diagnosed SLE patients without TP at registration were enrolled. The least absolute shrinkage and selection operator (LASSO) method was used for variable selection. The final model was developed using multivariate Cox regression and displayed as a nomogram. Internal validation was achieved using enhanced Bootstrap resampling., Results: During follow-up, thrombocytopenia developed in 80 (3.52%) of 2270 lupus patients. The final risk prediction model incorporated six predictors: baseline SDI score ≥ 1 (HR 2.207, 95% CI 1.350-3.609, p = 0.002), hemolytic anemia (HR 1.953, 95% CI 1.017-3.750, p = 0.044), low complement level (HR 2.351, 95% CI 1.004-5.505, p = 0.049), positive anti-β2GPI antibody (HR 1.805, 95% CI 1.084-3.004, p = 0.024), positive Coombs test (HR 1.878, 95% CI 1.123-3.141, p = 0.017), and positive anti-histone antibody (HR 1.595, 95% CI 1.017-2.587, p = 0.059). The model's performance was indicated by C-index values for risk prediction at one, two, and three years, which were 0.741 (0.660-0.823), 0.730 (0.655-0.805), and 0.710 (0.643-0.777), respectively; and Brier scores of 0.018 (0.012-0.024), 0.025 (0.017-0.032), and 0.037 (0.027-0.046), respectively. Calibration curves were drawn and situated near the diagonal line., Conclusions: This study developed the first risk prediction model for TP onset in lupus patients. Patients with baseline organ damage, hemolytic anemia, low complement, positive anti-histone antibody, positive anti-β2GPI antibody, or positive Coombs test were identified as being at high risk for thrombocytopenia and require further clinical attention., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Peking Union Medical College Hospital and conducted in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). All the patients were provided with written informed consent for participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Rheumatoid arthritis (RA) and cardiovascular disease (CVD) are both the chronic inflammatory disease. To investigate the influence of secondary atherosclerosis on arthritis mice, we treated the ApoE -/- mice with K/BxN serum and high fat diet (HFD), and subsequently assessed the phenotypes as well as immune profiles of K/BxN serum and HFD induced ApoE -/- mice. We found that HFD treatment aggravated the hyperlipidemia, atherosclerotic lesions, ankle swelling and arthropathy of mice. We further demonstrated that HFD altered the gut microbiota and metabolism, intestinal homeostasis and Th17/Treg cell balance in lamina propria lymphocytes. Moreover, HFD decreased the number of Peyer' s patches and altered the expression profiling of gut immune cells. In addition, HFD increased the number of aortic leukocytes and macrophages, then aggravated the atherosclerosis in aorta, which led to greater inflammation in mice aorta and aortic root. Collectively, our study indicated that HFD aggravated the arthritis and atherosclerosis, which may be contributed by microbiota dysbiosis, the intestinal permeability and disrupted immunological homeostasis., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by Beijing Ethics Committees of Peking Union Medical College Hospital, approval number JS-1195, and Animal Care and Use Committee of Institute of laboratory animal sciences, Chinese academy of medical sciences, approval number ILAS-PG-2015-002. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Aconitine has cardiotoxicity, but the mechanism of cardiotoxicity induced by aconitine is limited. The aim of this study was to investigate the mechanism of myocardial injury induced by aconitine., Methods: Using aconitine, ROS inhibitor N-acetylcysteine(NAC), the autophagy activitor Rapamycin (Rap) or the P38/MAPK pathway activitor Dehydrocorydaline treats H9C2 cells. CCK-8 assay was used to assay cell proliferation activity. Flow Cytometry was used to detect cell apoptosis. Dichloro-dihydrofluorescein diacetate was used to detect ROS levels. The expression of LC3 was detected by Immunofluorescence Staining. Western blotting detected the expression of related proteins. The mRNA levels of inflammatory factors were detected by RT-qPCR., Results: Aconitine inhibits cardiomyocyte proliferation, induces apoptosis and secretion of inflammatory factors. Aconitine activates the P38/MAPK/Nrf2 pathway, induces ROS increase, and promotes autophagy. NAC can inhibit proliferation inhibition, apoptosis, inflammation and P38/MAPK/Nrf2 pathway activation induced by aconitine. Rap and P38 activators can partially recover the effects of NAC on proliferation, apoptosis, inflammation and autophagy of cardiomyocytes., Conclusion: Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

The damnification of mitochondrion is often considered to be an important culprit of inflammatory bowel disease (IBD), however, there are fewer reports of mechanisms of mitochondria-mediated IBD treatment. Therefore, we first proposed to reboot mitochondrial energy metabolism to treat IBD by capturing the double-sided factor of ROS and creatine (Cr)-assisted energy adjustment. Herein, an oral Cr-modified selenium-based hyaluronic acid (HA) nanogel (HA Se -Cr nanogel) was fabricated for treatment of IBD, through ROS elimination and energy metabolism upgradation. More concretely, due to IBD lesion-specific positive charge and the high expression of CD44, HA Se -Cr nanogel exhibited dual targeted inflammatory bio-functions, and ROS-driven degradation properties in high-yield ROS levels in inflammation areas. As expected, multifunctional HA Se -Cr nanogel could effectively ameliorate IBD-related symptoms, such as mitochondrial biological function restoration, inhibition of M1-like macrophage polarization, gut mucosal reconstruction, microbial ecological repair, etc., thus excellently treating IBD. Overall, the proposed strategy underlined that the great potentiality of HA Se -Cr nanogel by restarting mitochondrial metabolic energy in colitis lesions, providing new a pavement of mitochondrion-mediated colitis treatment in clinical applications., Competing Interests: Declarations. Ethics approval and consent to participate: All animal care and experimental protocols comply with the relevant laws, regulations and standards concerning animal welfare ethics. This project has been supervised and approved by Laboratory Animal Welfare and Ethics Committee of Shanghai Jiaotong University (ICCUC NO. 2020-09-XLM-03). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The association between the geriatric nutritional risk index (GNRI) and osteosarcopenia in older adults with type 2 diabetes mellitus (T2DM) is not clear., Methods: A total of 573 individuals with T2DM were included in this cross-sectional study. Osteosarcopenia was defined as the presence of both osteoporosis and sarcopenia. Appendicular skeletal muscle mass and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry to diagnose sarcopenia and osteoporosis. Multivariate analyses were used to assess the association between Geriatric Nutritional Risk Index (GNRI) and osteosarcopenia., Results: The patients were divided into four groups: robust (n = 367), osteoporosis alone (n = 154), sarcopenia alone (n = 29), and osteosarcopenia (n = 23). The GNRI was the lowest in osteosarcopenia group and was positively correlated with skeletal muscle index (SMI) (r = 0.122, p = 0.004), grip strength (r = 0.154, p < 0.001), gait speed (r = 0.123, p = 0.004), and BMD of lumbar spine 2-4, femoral neck, and total hip (r = 0.137, p = 0.002; r = 0.096, p = 0.028; r = 0.086, p = 0.049, respectively). In the logistic regression model low GNRI was significantly associated with an increased risk of osteosarcopenia (adjusted OR, 4.164; 95% CI, 1.283-13.514, p = 0.018). Age provided a discriminatory effect of osteosarcopenia with an area under the curve (AUC) of 0.764. When GNRI values were added to the model, the value of the ROC curve was further improved, with an AUC of 0.842., Conclusion: Low GNRI was associated with an increased risk of osteosarcopenia in older adults with T2DM. Comprehensive clinical evaluation of nutritional status by a simple tool such as GNRI might be helpful for early identification of those at high risk for osteosarcopenia in older diabetic individuals., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Research Ethics Boards at Xuanwu Hospital (CTR-IPR-2019002). Written informed consent was obtained from all participants. In accordance with the Declaration of Helsinki, all our methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Chinese jujube (Ziziphus jujuba Mill.), also called Chinese date, is one of the oldest and widely cultivated fruit trees with great economic values, which, at least, can be attributed to the melliferous flower with highly developed nectary that can secret huge amount of nectar in a rather tiny floral size. However, the morphological nature, metabolic products, developmental process, as well as molecular and regulatory mechanisms of jujube nectary remain largely unknown., Results: Here, we selected Z. jujuba 'Dongzao' as a system to address these questions. We uncovered that the jujube nectary is an annular or donut-shaped secretory protrusion that surrounds the base of the carpels, along with emerald and glistening hues, which can produce a bulk honey with many metabolic compounds (e.g. saccharides and flavonoids) that has a high nutritional value and benefit for human health. The development of jujube nectary is a dynamic process of earlier cell division followed by later cell expansion. We also identified putative genes associated with the nectary development and found that the CRABS CLAW (CRC) ortholog (ZjCRC) is the key to nectary development: the gene is highly expressed in nectary; ectopic expression of it in the Arabidopsis crc-1 mutant rescued the lost nectary (also the carpel and silique defects). We also demonstrated that a MADS-box transcription factor ZjAGAMOUS1 (ZjAG1) is required for the direct activation of ZjCRC expression., Conclusions: Taken together, our results not only provide a comprehensive portrait of the jujube nectary, but also pave the way to effective utilization of jujube and other woody crops., (© 2024. The Author(s).)

Background: To assess the long-term outcomes of patients with glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE) who underwent Ahmed glaucoma valve (AGV) implantation combined with phacoemulsification and intraocular lens (IOL) implantation surgery., Methods: In this non-comparative retrospective case series study, twelve patients with uncontrolled GS-ICE and cataract underwent Ahmed aqueous shunt combined with phacoemulsification and IOL implantation surgery at Beijing Tongren Eye Center between June 2014 and June 2022. Main medical records included best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of antiglaucoma medications (AGM), corneal status and further surgical interventions. Surgical success was defined as a postoperative IOP ≥ 6mmHg and ≤ 21mmHg without (complete success) or with/without (qualified success) topical AGM and vision of at least light perception during the follow-up period., Results: Twelve eyes of twelve patients were reviewed. Preoperative IOP was decreased from a mean of 38.5 ± 6.7 mmHg on 3.3 ± 0.9 AGM to a mean of 16.3 ± 4.3 mmHg (P<0.001) on 0.6 ± 1.1 medications (P<0.001) at the last follow-up (47.0 ± 24.7 months). Eight eyes (66.7%) had stable vision or at least one line improvement than that before surgery. Eight eyes (66.7%) achieved qualified success and six eyes (50.0%) achieved complete success after surgery. The surgical procedure had a qualified survival of 91.7% at 1 year, 82.5% at 3 years, 72.2% at 5 years, and 48.1% at 7 years., Conclusion: AGV implantation combined with phacoemulsification and IOL implantation seems to be an effective method in IOP control and vision maintain for patients with GS-ICE. The combined surgical procedure may be a reliable option for those GS-ICE patients with coexisting cataract., (© 2024. The Author(s).)

Background: Congenital rib deformity is a common thoracic deformity that has a potentially far-reaching impact on the growth and lung function development of young children. Early diagnosis and accurate assessment of congenital rib deformity is of great importance. This study was to retrospectively analyze the number, location, and types of deformities, imaging features as well as clinical symptoms of children with congenital rib deformities., Methods: Children who were diagnosed with congenital rib deformities between October 2019 and October 2021 in our hospital were included in this study. The rib deformities were analyzed according to the imaging results of chest X-ray and 3D volume rendering multidetector computed tomography (MDCT). The data were analyzed using SPSS 22.0., Results: A total of 472 male and 186 female children with rib deformities were detected in this study, with a male to female ratio of approximately 2.54:1. Of the deformed ribs, 417 (63.4%) were located on the right side, usually single and unilateral. The most common type of the detected rib deformity were bifid ribs (95.14%). Rib deformity was most common in the fourth rib (46.62%). The majority (76.16%, n = 428) of rib deformities were incidental findings and asymptomatic., Conclusions: Congenital rib deformities in pediatric patients included in our hospital were more frequently observed in males than females, more frequently detected on the right than on the left side. The most common type of rib deformity is the bifid rib. MDCT examination are of great value in the diagnosis of rib deformity and can help guide clinical treatment., (© 2024. The Author(s).)

Background: Schizophrenia is associated with a high mortality rate due to the high risk of suicide. However, there is still a lack of evidence on the gender-specific risk factors for suicide among people with schizophrenia. In this study, we aimed to measure the sociodemographic and clinical correlates of suicide deaths in different genders among people with schizophrenia., Methods: Data on patients with schizophrenia from 2013 to 2021 in Guangzhou, China were obtained from the National Information System for Psychosis (NISP), involving a total of 33,080 patients. Cox regression and Fine-Gray models were used to explore the sociodemographic and clinical risk factors for suicide mortality in different genders., Results: The overall age-standardized mortality rates due to suicide were 133.89 (95% CI: 124.31-143.47) per 100,000 person-years for females and 163.25 (95% CI: 152.92-173.59) per 100,000 person-years for males. To be specific, lack of medical insurance, history of non-treatment, and history of suicidal behavior was associated with a higher risk for suicide mortality for females, while an age of 35-54, being hospitalized once, and the age of onset being > 28 years were linked to lower risk for suicide mortality for males. For both genders, a lower risk for suicide mortality was observed in patients at an older age (≥ 55 years) and with a history of hospitalization more than once, and a higher suicide mortality risk was found in married patients and those residing in rural areas., Conclusion: The present study found that gender differences should be taken into account in the development of suicide prevention programs for people with schizophrenia, and future research is still required to verify our preliminary results., (© 2024. The Author(s).)

Background and Objectives: The purpose of this study was to investigate the survival benefit of Stereotactic Body Radiotherapy (SBRT) versus lenvatinib as first-line therapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT)., Materials and Methods: 147 HCC patients with PVTT were included in this retrospective study, 70 were treated with SBRT and 77 of were treated with lenvatinib. Propensity score matching (PSM) analysis was employed to balance the differences in baseline characteristics between the two groups. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between the two groups. In addition, the safety of patients in both groups was also evaluated., Results: After PSM, 38 patients were matched in each of the two groups. The median OS was 14.5 (95% CI: 10.1-18.9) and 11.1 (95% CI: 9.3-12.9) months in the SBRT and lenvatinib groups, respectively (P = 0.014). The median PFS was 6.8 (95% CI: 5.1-8.5) and 5.0 (95% CI: 3.0-7.0) months, respectively (P = 0.010). The 1-, 2-years OS rates in the two groups were 65.8% vs. 39.5% and 31.6% vs. 10.5%, respectively. The 6-, 12-months PFS rates in the two groups were 57.9% vs. 44.7% and 28.9% vs. 10.5%, respectively. In addition, the SBRT group had a better ORR than the lenvatinib group (52.6% vs. 23.7%, P = 0.009). Patients with good response to SBRT had better survival. Cox proportional hazard model showed that SBRT was an important prognostic factor for OS and PFS. The incidence of hypertension (34.2% vs. 0%) was higher in the LEN group, however, both treatment modalities were well tolerated in the two groups of patients., Conclusion: In HCC patients with PVTT, SBRT had a better survival benefit than Lenvatinib treatment as first-line therapy., (© 2024. The Author(s).)

Background: To establish the pathological diagnosis of UTUC before treatment is profitable. At present, the conventional pathological diagnostic methods have certain problems. Besides, the urine-based DNA methylation test have been already utilized to detect bladder cancer., Objective: To evaluate the sensitivity and specificity of DNA methylation plus 17 genes mutation test and compare the combined test with cytology., Materials and Methods: We included 45 patients from April 2019 to May 2022, all of whom underwent radical nephroureterectomy (RNU), nephrectomy, diagnostic ureteroscopy or tissue biopsy. Before surgery, the urine samples were collected for DNA methylation plus 17 genes mutation test and cytology. The test performance was calculated, and comparative ROC curves were drawn., Results: The median age of the patients was 67 years. The Kappa value of the DNA methylation plus 17 genes mutation test and tissue pathology was 0.59 (p<0.001). The sensitivity/specificity/PPV/NPV of DNA methylation plus 17 genes mutation test was 86/80/94/62% compared with 29/100/100/29% for cytology. The AUC of DNA methylation plus 17 genes mutation test was 0.829 (p<0.001).The mutated gene proportion of UTUC patients was 51.43% for TERT and 25.71% for TP53., Conclusion: The test performance of DNA methylation plus 17 genes mutation test was satisfactory, which may replace cytology in the future. Further multicenter studies with larger samples are needed to confirm the clinical value of this promising method., Novelty & Impact Statements: We evaluated the diagnostic efficacy of a urine-based liquid biopsy for the detection of UTUC and compared the combined test with cytology. We found satisfactory results and concluded that the test could partly replace cytology. Further studies are needed., (© 2024. The Author(s).)

Background: Frailty is one of the most significant issues related to human aging. Although studies have confirmed the association of mental and cognitive disorders with frailty, the association might be influenced by age, since oldest-old adults are more likely to have adverse health outcomes. Thus, this study aimed to examine independent and combined associations of mental health and cognitive function with frailty in oldest-old adults using data from the Chinese Longitudinal Healthy Longevity Survey in 2018., Methods: A sum of 6,891 and 3,171 older adults aged 80 and older were included in this study when analyzing the association of depression and cognitive impairment with frailty, respectively. Frailty was measured by the Study of Osteoporotic Fractures frailty index, depression was assessed by the Center for Epidemiologic Studies Depression Scale, and cognitive impairment was evaluated by the Chinese version of modified Mini-Mental State Examination. Independent sample t-test, Chi-square tests, and logistic regression analyses were used to examine the associations of depression and cognitive impairment with frailty., Results: Older persons with depression or cognitive impairment had a higher chance of frailty. The adjusted odds ratio (OR) of frailty was 1.27 (95% CI: 1.01, 1.59, p = 0.044) in those with depression, and 1.85 (95% CI: 1.14, 3.01, p = 0.013) in those with cognitive impairment. Compared to adults who had neither depression nor cognitive impairment, those with either depression or cognitive impairment, and those with both depression and cognitive impairment had a significantly higher likelihood of frailty (adjusted OR: 1.61, 95% CI: 1.07, 2.41; and adjusted OR: 4.03, 95% CI: 2.05, 7.94)., Conclusions: The findings suggest that depression and cognitive impairment are associated with frailty. The concurrence of depression and cognitive impairment has an additive effect on frailty in oldest-old population., (© 2024. The Author(s).)

Purpose: This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients., Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis., Results: This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p < 0.0001], and fewer overall complications [OR 0.62; 95% CI 0.45 to 0.86; p = 0.004], but a higher recurrence rate [OR 7.83; 95% CI 4.32 to 14.19; p < 0.00001]. There were no significant differences between the two groups in terms of operative time, minor complications (Clavien-Dindo Grade 1-2), major complications (Clavien-Dindo Grade 3-5), changes in renal function at 12 months post-operation, RFS (Recurrence-Free Survival), and OS (Overall Survival)., Conclusion: The evidence provided by this meta-analysis indicates that the therapeutic effects of Cryoablation (CA) are similar to those of Robot-Assisted Partial Nephrectomy (RAPN) in terms of perioperative outcomes and renal function. However, the recurrence rate of tumors treated with CA is significantly higher., Systematic Review Registration: The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023465846)., (© 2024. The Author(s).)

Background: Hypoxic pulmonary vasoconstriction is the most important regulatory mechanism by which right-to-left shunts decrease during one-lung ventilation (OLV), but the effects of pulmonary microarterial thrombosis and impaired HPV after SARS-CoV-2 infection on intrapulmonary shunt during OLV remain unknown. The aim of this study was to observe the changes of intrapulmonary shunt in patients undergoing thoracoscopic partial pneumonectomy at different periods after SARS-CoV-2 infection compared with patients without SARS-CoV-2 infection history., Methods: A total of 80 patients who underwent elective thoracoscopic partial lung resection and were classified as American Society of Anaesthesiologists (ASA) grades I-II were selected and divided into 4 groups (n = 20 in each group): patients not infected with SARS-CoV-2 (Group A), patients infected with SARS-CoV-2 for 5-8 weeks (Group B), patients infected with SARS-CoV-2 for 9-12 weeks (Group C), and patients infected with SARS-CoV-2 for 13-16 weeks (Group D). For all patients, the same anaesthesia method was adopted, and anaesthesia was maintained with propofol, remifentanil, and cisatracurium. Radial artery and mixed venous blood gases were measured at 10 min of two-lung ventilation (TLV), 15 min of one-lung ventilation (OLV15), and 30 min of OLV (OLV30) in the lateral recumbent position to calculate the intrapulmonary shunt. Multiple linear regression analysis was employed to investigate the association between intrapulmonary shunt and SARS-CoV-2 infection., Results: Qs/Qt at TLV was significantly higher in Groups B and C than in Group A (P < 0.05), and PaO 2 at TLV was significantly lower in Groups B and C than in Group A (P < 0.05). Qs/Qt values at OLV15 and OLV30 were significantly higher in Group B, C or D than in Group A (P < 0.05), and PaO 2 values at OLV15 and OLV30 were significantly lower in Groups B, C or D than in Group A (P < 0.05). Multiple linear regression analysis revealed that SARS-CoV-2 infection (95%CI -4.245 to -0.679, P = 0.007) was an independent risk factor for increased intrapulmonary shunt during TLV, while SARS-CoV-2 infection (95%CI 0.124 to 3.661, P = 0.036), exacerbation of COVID-19 clinical classification (95%CI -5.203 to -1.139, P = 0.003), and persistent symptoms (95%CI -12.122 to -5.522, P < 0.001) were independent risk factors for increased intrapulmonary shunt during OLV after SARS-CoV-2 infection., Conclusion: SARS-CoV-2 infection increased intrapulmonary shunt and reduced oxygenation. Although oxygenation improved at TLV after 13-16 weeks of infection, intrapulmonary shunt and oxygenation under OLV took longer to recover., Trial Registration: Chinese Clinical Trial Registry, Retrospectively registered, Full date of first registration: 17/05/2023, Registration number: ChiCTR2300071539., (© 2024. The Author(s).)

Objective: Trabeculectomy and non-penetrating trabecular surgery are common operations for glaucoma. This meta-analysis aims to compare the effect of trabeculectomy and non-penetrating trabecular surgery in postoperative astigmatism of patients with glaucoma., Methods: A systematic literature search was performed for studies comparing trabeculectomy and non-penetrating trabecular surgery in patients with glaucoma. The time frame for the search was from the time of construction to April 2024. There were no restrictions regarding study type or type of glaucoma. The endpoint was the surgically induced astigmatism assessed 6 months after operation. We conducted this meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)., Results: Five eligible studies were included in this meta-analysis and presented data for 359 eyes with various types of glaucoma at different stages. The results revealed an increase in astigmatism in patients with glaucoma after trabeculectomy and non-penetrating trabecular surgery. Trabeculectomy had a higher incidence of astigmatism than in the non-penetrating trabecular surgery group at or around 6 months postoperatively, and the difference was statistically significant. (SMD = 0.40, 95% CI = 0.19 to 0.61, P = 0.02)., Conclusion: Our results demonstrated that both trabeculectomy and non-penetrating trabecular surgery could increase astigmatism until 6 months after operation. Moreover, non-penetrating trabecular surgery group seems to have less influence on astigmatism., Trial Registration Number: CRD42024517708., (© 2024. The Author(s).)

Background: The present study elucidates a common significant postoperative complication of micropulse transscleral laser treatment (mTLT) and explores its potential management strategies for younger patients with good central vision., Case Presentation: Three younger Chinese glaucoma patients with good central vision maintained high intraocular pressures (IOPs) (36, 25, and 30 mmHg) on maximally tolerated topical anti-glaucoma medications. All patients were treated with mTLT because of a higher risk of complications with filtering surgery. After the procedure, their best-corrected visual acuities were not significantly changed, IOPs were significantly decreased, and the number of topical anti-glaucoma medicines was gradually decreased. However, all patients complained about reduced near visual acuity (NVA) for 1-5 months. Slit-lamp examination revealed pupillary dilation, and binocular accommodative function examination indicated accommodation loss. After treatment with 2% topical pilocarpine, all patients reported an improvement in NVA. Among them, we could observe pupillary constriction, recovery of accommodation function, and improved NVA, even discontinuation of pilocarpine in Patient 2., Conclusion: In younger patients with good central vision, topical pilocarpine might ameliorate accommodation loss and pupillary dilation after mTLT., (© 2024. The Author(s).)

Background: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients., Methods: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients., Results: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7., Conclusion: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients., (© 2024. The Author(s).)

Background: This study investigated the characteristics of Monson's sphere in Chinese young adult females with individual normal occlusion to provide a reference for oral rehabilitation in prosthodontic and orthodontic treatments., Methods: Points at the dental cusps and incisal edges were selected from 51 digital mandibular dental models of Chinese young adult females (aged 18-22 years) with individual normal occlusion. Monson's spheres were fitted to the selected points based on the least-squares principle and the radii were calculated. The deviation of each selected point from its relative spherical surface was also calculated. The radii and deviations of these points were examined using conventional descriptive statistics and distributions of the most deviated points inside and outside the spheres were analyzed., Results: The mean radius of Monson's sphere in Chinese young adult females was 79.60 ± 14.13 mm. The deviation of each selected point from its relative sphere surface was 0.38 ± 0.30 mm. The maximum deviations inside and outside the sphere were 0.93 ± 0.25 mm and 0.95 ± 0.30 mm, respectively. The most deviated points outside the spheres were mainly distributed at the distolingual cusps of the mandibular second permanent molars (31.37%), while those inside the spheres were mainly distributed at the mesiolingual cusps of the mandibular first permanent molars (45.10%)., Conclusions: The radius of Monson's sphere in Chinese young adult females was smaller than the classic four-inch value suggested by Monson. Deviation was observed from all selected points to their Monson's sphere surface, with the most deviated points distributed primarily in the molar region., (© 2024. The Author(s).)

Background: While growing evidence suggests a relationship between migraine and cardiovascular disease, the genetic evidence for a causal relationship between migraine and cardiovascular disease is still scarce. Investigating the causal association between migraine and cardiovascular disease is vital., Methods: We carried out a bidirectional Mendelian randomization (MR) study including discovery samples and replication samples using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables. Four different MR techniques-Inverse variance weighted (IVW), MR ‒Egger, weighted median, and weighted mode-as well as various sensitivity analyses-Cochran's Q, IVW radial, leave-one-out (LOO), and MR-PRESSO-were utilized to investigate the causal relationship between cardiovascular disease and migraine., Results: The protective causal effects of genetically predicted migraine on coronary artery disease (OR, 0.881; 95% CI 0.790-0.982; p = 0.023) and ischemic stroke (OR, 0.912; 95% CI 0.854-0.974; p = 0.006) were detected in forward MR analysis but not in any other cardiovascular disease. Consistently, we also discovered protective causal effects of coronary atherosclerosis (OR, 0.865; 95% CI 0.797-0.940; p = 0.001) and myocardial infarction (OR, 0.798; 95% CI 0.668-0.952; p = 0.012) on migraine in reverse MR analysis., Conclusion: We found a potential protective effect of migraine on coronary artery disease and ischemic stroke and a potential protective effect of coronary atherosclerosis and myocardial infarction on migraine. We emphasised epidemiological and genetic differences and the need for long-term safety monitoring of migraine medications and future research to improve cardiovascular outcomes in migraine patients., (© 2024. The Author(s).)

Background: Bladder cancer (BLCA) poses a significant global health challenge due to its high incidence, poor prognosis, and limited treatment options., Aims and Objectives: This study aims to investigate the association between two specific polymorphisms, CYP1A2-163 C/A and CYP1A2-3860G/A, within the Cytochrome P450 1A2 (CYP1A2) gene and susceptibility to BLCA., Methods: The study employed a case-control design, genotyping 340 individuals using Polymerase Chain Reaction-High-Resolution Melting Curve (PCR-HRM). Various genetic models were applied to evaluate allele and genotype frequencies. Genetic linkage analysis was facilitated using R packages., Results: The study reveals a significant association with the - 163 C/A allele, particularly in the additive model. Odds ratio (OR) analysis links CYP1A2-163 C/A (rs762551) and CYP1A2-3860G/A(rs2069514) polymorphisms to BLCA susceptibility. The rs762551 C/A genotype is prevalent in 55% of BLCA cases and exhibits an OR of 2.21. The A/A genotype has an OR of 1.54. Regarding CYP1A2-3860G/A, the G/A genotype has an OR of 1.54, and the A/A genotype has an OR of 2.08. Haplotype analysis shows a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. This study underscores associations between CYP1A2 gene variants, particularly rs762551 (CYP1A2-163 C/A), and an increased susceptibility to BLCA. Haplotype analysis of 340 individuals reveals a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%., Conclusion: In conclusion, the - 163 C/A allele, C/A genotype of rs762551, and G/A genotype of rs2069514 emerge as potential genetic markers associated with elevated BLCA risk., (© 2024. The Author(s).)

Background: T cells play a pivotal role in chemotherapy-triggered anti-tumor effects. Emerging evidence underscores the link between impaired anti-tumor immune responses and resistance to paclitaxel therapy in triple-negative breast cancer (TNBC). Tumor-related endothelial cells (ECs) have potential immunoregulatory activity. However, how ECs regulate T cell activity during TNBC chemotherapy remains poorly understood., Methods: Single-cell analysis of ECs in patients with TNBC receiving paclitaxel therapy was performed using an accessible single-cell RNA sequencing (scRNA-seq) dataset to identify key EC subtypes and their immune characteristics. An integrated analysis of a tumor-bearing mouse model, immunofluorescence, and a spatial transcriptome dataset revealed the spatial relationship between ECs, especially Tumor necrosis factor receptor (TNFR) 2+ ECs, and CD8+ T cells. RNA sequencing, CD8+ T cell proliferation assays, flow cytometry, and bioinformatic analyses were performed to explore the immunosuppressive function of TNFR2 in ECs. The downstream metabolic mechanism of TNFR2 was further investigated using RNA sequencing, cellular glycolysis assays, and western blotting., Results: In this study, we identified an immunoregulatory EC subtype, characterized by enhanced TNFR2 expression in non-responders. By a mouse model of TNBC, we revealed a dynamic reduction in the proportion of the CD8+ T cell-contacting tumor vessels that could co-localize spatially with CD8+ T cells during chemotherapy and an increased expression of TNFR2 by ECs. TNFR2 suppresses glycolytic activity in ECs by activating NF-κB signaling in vitro. Tuning endothelial glycolysis enhances programmed death-ligand (PD-L) 1-dependent inhibitory capacity, thereby inducing CD8+ T cell suppression. In addition, TNFR2+ ECs showed a greater spatial affinity for exhausted CD8+ T cells than for non-exhausted CD8+ T cells. TNFR2 blockade restores impaired anti-tumor immunity in vivo, leading to the loss of PD-L1 expression by ECs and enhancement of CD8+ T cell infiltration into the tumors., Conclusions: These findings reveal the suppression of CD8+ T cells by ECs in chemoresistance and indicate the critical role of TNFR2 in driving the immunosuppressive capacity of ECs via tuning glycolysis. Targeting endothelial TNFR2 may serve as a potent strategy for treating TNBC with paclitaxel., (© 2024. The Author(s).)

Due to the rapid development of stem cell technology, there have been tremendous advances in molecular biological and pathological research, cell therapy as well as organoid technologies over the past decades. Advances in genome editing technology, particularly the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-related protein 9 (Cas9), have further facilitated the rapid development of stem cell researches. The CRISPR-Cas9 technology now goes beyond creating single gene editing to enable the inhibition or activation of endogenous gene loci by fusing inhibitory (CRISPRi) or activating (CRISPRa) domains with deactivated Cas9 proteins (dCas9). These tools have been utilized in genome-scale CRISPRi/a screen to recognize hereditary modifiers that are synergistic or opposing to malady mutations in an orderly and fair manner, thereby identifying illness mechanisms and discovering novel restorative targets to accelerate medicinal discovery investigation. However, the application of this technique is still relatively rare in stem cell research. There are numerous specialized challenges in applying large-scale useful genomics approaches to differentiated stem cell populations. Here, we present the first comprehensive review on CRISPR-based functional genomics screening in the field of stem cells, as well as practical considerations implemented in a range of scenarios, and exploration of the insights of CRISPR-based screen into cell fates, disease mechanisms and cell treatments in stem cell models. This review will broadly benefit scientists, engineers and medical practitioners in the areas of stem cell research., (© 2024. The Author(s).)

Background: Nasopharyngeal carcinoma (NPC) is 22nd most common cancer that occurs all over the world, but the prevalence rate can exhibit significant geographical differences. The Global Burden of Disease (GBD) database provides data related to the incidence, mortality, and disease burden of NPC worldwide from 1990 to 2019. We have designed this study in order to evaluate the potential effectiveness of health care policies and strategies for NPC prevention, diagnosis and treatment in different countries or regions around the world., Methods: We used for the first time two distinct indicators, EAPC-ASIR and EACP-ASDR, to perform cluster analysis on 200 countries or regions around the world., Results: 200 countries or regions could be divided into five diverse groups. Group 1: The incidence rate showed an increasing trend whereas the mortality rate depicted a decreasing trend. Group 2: Morbidity as well as mortality showed a slight increase; Group 3: Morbidity as well as mortality increased significantly; Group 4: Morbidity and mortality decreased significantly; Group 5: Both morbidity as well as mortality decreased slightly. Moreover, in the context of a global decline in NPC incidence, mortality and disease burden, Group 3 countries, including: "Turkmenistan", "Bosnia and Herzegovina", "Dominican Republic", "Bulgaria", "Lesotho", "Cabo Verde", "Romania", "Cuba", "Jamaica", "Azerbaijan", "Uzbekistan", "Chad", "Belize" and "Ukraine" displayed a significant increase in morbidity, mortality, and disease burden, thus indicating a dangerous trend., Conclusion: It is suggested that the medical and health policies formulated by the countries in Group 3 for NPC, as well as their capacity for conducting censuses, preventing, diagnosing, and treating diseases, need to be substantially strengthened., (© 2024. The Author(s).)

Background: Circadian rhythm (CR) disturbance is intricately associated with Parkinson's disease (PD). However, the involvement of CR-related mechanisms in the pathogenesis and progression of PD remains elusive., Methods: A total of 141 PD patients and 113 healthy participants completed CR-related clinical examinations in this study. To further investigate the CR-related mechanisms in PD, we obtained datasets (GSE7621, GSE20141, GSE20292) from the Gene Expression Omnibus database to identify differentially expressed genes between PD patients and healthy controls and further selected CR-related genes (CRRGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) followed by logistic algorithms were employed to identify the hub genes and construct a diagnostic model. The predictive performance was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses in the training set and external validation sets. Finally, RT‒qPCR and Western blotting were conducted to verify the expression of these hub genes in blood samples. In addition, Pearson correlation analysis was utilized to validate the association between expression of hub genes and circadian rhythm function., Results: Our clinical observational study revealed that even early-stage PD patients exhibited a higher likelihood of experiencing sleep disturbances, nocturnal hypertension, reverse-dipper blood pressure, and reduced heart rate variability compared to healthy controls. Furthermore, 4 CR-related hub genes (AGTR1, CALR, BRM14, and XPA) were identified and subsequently incorporated as candidate biomarkers to construct a diagnostic model. The model showed satisfactory diagnostic performance in the training set (AUC = 0.941), an external validation set GSE20295 (AUC = 0.842), and our clinical centre set (AUC = 0.805). Additionally, the up-regulation of CALR, BRM14 and the down-regulation of AGTR1, XPA were associated with circadian rhythm disruption., Conclusion: CR disturbance seems to occur in the early stage of PD. The diagnostic model based on CR-related genes demonstrated robust diagnostic efficacy, offering novel insights for future clinical diagnosis of PD and providing a foundation for further exploration into the role of CR-related mechanisms in the progression of PD., (© 2024. The Author(s).)

Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines., (© 2024. The Author(s).)

The reprogramming of tumor metabolism presents a substantial challenge for effective immunotherapy, playing a crucial role in developing an immunosuppressive microenvironment. In particular, the degradation of the amino acid L-tryptophan (Trp) to kynurenine (Kyn) by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) is one of the most clinically validated pathways for immune suppression. Thus, regulating the Trp/Kyn metabolism by IDO1 inhibition represents a promising strategy for enhancing immunotherapy. Herein, metabolism-regulated nanoparticles are prepared through metal coordination-driven assembly of an IDO1 inhibitor (NLG919) and a stimulator of interferon genes (STING) agonist (MSA-2) for enhanced immunotherapy. After intravenous administration, the assembled nanoparticles could efficiently accumulate in tumors, enhancing the bioavailability of NLG919 and down-regulating the metabolism of Trp to Kyn to remodel the immunosuppressive tumor microenvironment. Meanwhile, the released MSA-2 evoked potent STING pathway activation in tumors, triggering an effective immune response. The antitumor immunity induced by nanoparticles significantly inhibited the development of primary and metastatic tumors, as well as B16 melanoma. Overall, this study provided a novel paradigm for enhancing tumor immunotherapy through synergistic amino acid metabolism and STING pathway activation., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Xiuying Duan et al.)

Purpose: To evaluate the value of five indicators in predicting OVCF through a retrospective case-control study, and explore the internal correlation of different indicators., Method: We retrospectively enrolled patients over 50 years of age who had been subjected to surgery for fragility OVCF at China Japan Friendship Hospital from January 2021 to September 2023. Demographic characteristics, T-score based on dual-energy X-ray absorptiometry (DXA), CT-based Hounsfield unit (HU) value, vertebral bone quality (VBQ) score based on magnetic resonance imaging (MRI), relative cross-sectional area (rCSA) and the rate of fat infiltration (FI) of paraspinal muscle were collected. A 1:1 age- and sex-matched, fracture-free control group was established from patients admitted to our hospital for lumbar spinal stenosis or lumbar disk herniation., Results: A total of 78 patients with lumbar fragility OVCF were included. All the five indicators were significantly correlated with the occurrence of OVCFs. Logistic regression analysis showed that average HU value and VBQ score were significantly correlated with OVCF. The area under the curve (AUC) of VBQ score was the largest (0.89). There was a significantly positive correlation between average T-score, average HU value and average total rCSA. VBQ score was significantly positive correlated with FI., Conclusion: VBQ score and HU value has good value in predicting of fragility OVCF. In addition to bone mineral density, we should pay more attention to bone quality, including the fatty signal intensity in bone and the FI in paraspinal muscle., (© 2024. The Author(s).)

Immunotherapy shows great therapeutic potential for long-term protection against tumor relapse and metastasis. Innate immune sensors, such as cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), dissolve DNA and induce type I interferon. Through activation of the cGAS/STING pathway, chemotherapy drugs and reversine (REV) may provide synergetic anti-tumor effects. Here, we prepared drug-loaded cell membrane hybrid lipid nanovesicles (LEVs) (designated LEV@DOX@REV) by fusion of cell membranes, phospholipids, doxorubicin (DOX), and REV, to realize accurate delivery to tumors and chemo-immunotherapy. The cell membranes of LEVs confer "homing" abilities. DOX can induce immunogenic cell death as a result of its specific immunomodulatory effects, which promotes the maturation of immune cells and improves the microenvironment of the immune system. REV is proven to efficiently activate cGAS/STING signaling, thereby enhancing the immune system. The antitumor efficacy of LEV@DOX@REV was evaluated in a 4T1 subcutaneous tumor xenograft model, a distant metastatic tumor model, and a liver metastatic tumor model. LEV@DOX@REV facilitated the infiltration of cytotoxic T lymphocytes within tumors, increased the secretion of proinflammatory cytokines, and modified the tumor microenvironment. In conclusion, LEV@DOX@REV displayed favorable antitumor effects and extended the survival of tumor-bearing mice. We therefore successfully developed nanoparticles capable of enhancing immune activation that have potential therapeutic applications for cancer immunotherapy., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ruijie Qian et al.)

Background: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology., Result: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4 + and CD8 + T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs., Conclusion: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts., (© 2024. The Author(s).)

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer., (© 2024. The Author(s).)

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy., (© 2024. The Author(s).)

CRISPR-based gene therapy offers precise targeting and specific editing of disease-related gene sequences, potentially yielding long-lasting treatment effects. However, efficient delivery remains a significant challenge for its widespread application. In this study, we design a novel short peptide-conjugated bioreducible polymer named TSP scp as a safe and effective delivery vector for the CRISPR system. Our results show that TSP scp markedly boosts transcriptional activation and genome editing activities of multiple CRISPR systems as confirmed by decomposition-seq and Deep-seq, which is resulted from its capability in facilitating delivery of plasmid DNA by promoting cellular uptake and lysosomal escape. Additionally, TSP scp further enhances genome editing of CRISPR by delivery of minicircle DNA, a condensed form of regular plasmid DNA. More importantly, TSP scp significantly improves delivery and genome editing of CRISPR system in vivo. In summary, our study highlights TSP scp as a promising delivery tool for CRISPR applications in vivo., (© 2024. The Author(s).)

Objective: To construct a nutrition support program for middle-aged and elderly patients with acute decompensated heart failure (ADHF) during hospitalization., Methods: Based on the JBI Evidence-Based Health Care Model as the theoretical framework, the best evidence was extracted through literature analysis and a preliminary nutrition support plan for middle-aged and elderly ADHF patients during hospitalization was formed. Two rounds of expert opinion consultation were conducted using the Delphi method. The indicators were modified, supplemented and reduced according to the expert's scoring and feedback, and the expert scoring was calculated., Results: The response rates of the experts in the two rounds of consultation were 86.7% and 100%, respectively, and the coefficient of variation (CV) for each round was between 0.00% and 29.67% (all < 0.25). In the first round of expert consultation, 4 items were modified, 3 items were deleted, and 3 items were added. In the second round of the expert consultation, one item was deleted and one item was modified. Through two rounds of expert consultation, expert consensus was reached and a nutrition support plan for ADHF patients was finally formed, including 4 first-level indicators, 7 s-level indicators, and 24 third-level indicators., Conclusion: The nutrition support program constructed in this study for middle-aged and elderly ADHF patients during hospitalization is authoritative, scientific and practical, and provides a theoretical basis for clinical development of nutrition support program for middle-aged and elderly ADHF patients during hospitalization., (© 2024. The Author(s).)

Background: Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear., Methods: Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration., Results: HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells., Conclusions: Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer., (© 2024. The Author(s).)

Background: PTEN loss has been identified in various tumor types and is linked to unfavorable clinical outcomes. In addition to PTEN mutation, multiple mechanisms contribute to PTEN loss during tumor development. However, the natural selection process of PTEN-deficient tumor cells remains unclear. Here, we aimed at further elucidating the role of PTEN-L in tumor progression., Methods: PTEN knockout cell lines were generated using CRISPR/Cas9 technology. Ni-NTA affinity column chromatography was employed for PTEN-L purification. Tumor cell metastasis was evaluated in murine models and observed using the IVIS Spectrum Imaging System. RNA-sequencing, western blotting, PCR, flow cytometry, and cell proliferation assays were employed to investigate tumor cell dormancy and related mechanisms., Results: The chemotherapeutic drugs, cisplatin, paclitaxel, and doxorubicin, induced tumor cells to secrete PTEN-long (PTEN-L), which shields PTEN-deficient tumor cells from chemotherapy-induced apoptosis better than it shields PTEN-intact cells. Further investigation revealed that PTEN-L treatment induced dormancy in PTEN-null tumor cells, characterized by an increase in p16 and p27 levels, cell-cycle arrest, reduced cell proliferation, and enhanced DNA repair. Furthermore, PTEN-L treatment selectively promoted the accumulation and growth of PTEN-null tumor cells in the lungs of C57BL/6J mice, while evading immune surveillance. Mechanistically, PTEN-L induced dormancy in PTEN-null tumor cells by activating the p38 signaling pathway. Addition of a p38 inhibitor effectively reversed dormancy and growth of PTEN-deficient tumor cells in the lungs. We also demonstrated that PTEN expression played a pivotal role in determining the outcome of PTEN-L-mediated antitumor therapy., Conclusions: In summary, PTEN-L was identified as a potent inducer of dormancy in PTEN-deficient tumor cells, which increased their efficient selection within the tumor microenvironment., (© 2024. The Author(s).)

Brasenia schreberi, a plant species traditionally utilized in Chinese medicine and cuisine, represents an early evolutionary stage among flowering plants (angiosperms). While the plastid genome of this species has been published, its mitochondrial genome (mitogenome) has not been extensively explored, with a notable absence of thorough comparative analyses of its organellar genomes. In our study, we had assembled the entire mitogenome of B. schreberi utilizing the sequencing data derived from both Illumina platform and Oxford Nanopore. The B. schreberi mitogenome mostly exists as six circular DNA molecules, with the largest being 628,257 base pairs (bp) and the smallest 110,220 bp, amounting to 1.49 megabases (Mb). Then we annotated the mitogenome of B. schreberi. The mitogenome encompasses a total of 71 genes: 40 of these are coding proteins genes (PCGs), 28 are genes for transfer RNA (tRNA), and the remaining 3 are genes for ribosomal RNA (rRNA). In the analysis of codon usage, we noted a unique codon preference specific to each amino acid. The most commonly used codons exhibited an average RSCU of 1.36, indicating a noticeable bias in codon selection. In the repeat sequence analysis, a total of 553 simple sequence repeats (SSRs) were identified, 1,822 dispersed repeats (comprising 1,015 forward and 807 palindromic repeats), and 608 long terminal repeats (LTRs). Additionally, in the analysis of homologous sequences between organelle genomes, we detected 38 homologous sequences derived from the plastid genome, each exceeding 500 bp, within the B. schreberi mitochondrial genome. Notably, ten tRNA genes (trnC-GCA, trnM-CAU, trnI-CAU, trnQ-UUG, trnN-GUU, trnT-GGU, trnW-CCA, trnA-UGC, trnI-GAU, and trnV-GAC) appear to have been completely transferred from the chloroplast to the mitogenome. Utilizing the Deepred-mt to predict the RNA editing sites in the mitogenome, we have identified 675 high-quality RNA editing sites in the 40 mitochondrial PCGs. In the final stage of our study, we performed an analysis of colinearity and inferred the phylogenetic relationship of B. schreberi with other angiosperms, utilizing the mitochondrial PCGs as a basis. The results showed that the non-coding regions of the B. schreberi mitogenome are characterized by an abundance of repetitive sequences and exogenous sequences, and B. schreberi is more closely related with Euryale ferox., (© 2024. The Author(s).)

Background: Aconitum carmichaelii Debx. has been widely used as a traditional medicinal herb for a long history in China. It is highly susceptible to various dangerous diseases during the cultivation process. Downy mildew is the most serious leaf disease of A. carmichaelii, affecting plant growth and ultimately leading to a reduction in yield. To better understand the response mechanism of A. carmichaelii leaves subjected to downy mildew, the contents of endogenous plant hormones as well as transcriptome sequencing were analyzed at five different infected stages., Results: The content of 3-indoleacetic acid, abscisic acid, salicylic acid and jasmonic acid has changed significantly in A. carmichaelii leaves with the development of downy mildew, and related synthetic genes such as 9-cis-epoxycarotenoid dioxygenase and phenylalanine ammonia lyase were also significant for disease responses. The transcriptomic data indicated that the differentially expressed genes were primarily associated with plant hormone signal transduction, plant-pathogen interaction, the mitogen-activated protein kinase signaling pathway in plants, and phenylpropanoid biosynthesis. Many of these genes also showed potential functions for resisting downy mildew. Through weighted gene co-expression network analysis, the hub genes and genes that have high connectivity to them were identified, which could participate in plant immune responses., Conclusions: In this study, we elucidated the response and potential genes of A. carmichaelii to downy mildew, and observed the changes of endogenous hormones content at different infection stages, so as to contribute to the further screening and identification of genes involved in the defense of downy mildew., (© 2024. The Author(s).)

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe 2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice., (© 2024. The Author(s).)

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation., (© 2024. The Author(s).)

Background: Yanghe Pingchuan decoction (YPD) has been used for asthma treatment for many years in China. We sought to understand the mechanism of YPD, and find more potential targets for YPD-based treatment of asthma., Methods: An ovalbumin-induced asthma model in rats was created. Staining (hematoxylin and eosin, Masson) was used to evaluate the treatment effect of YPD. RNA-sequencing was carried out to analyze global gene expression, and differentially expressed genes (DEGs) were identified. Analysis of the functional enrichment of genes was done using the Gene Ontology database (GO). Analysis of signaling-pathway enrichment of genes was done using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time reverse transcription-quantitative polymerase chain reaction was undertaken to measure expression of DEGs., Results: Pathology showed that YPD had an improvement effect on rats with asthma. RNA-sequencing showed that YPD led to upregulated and downregulated expression of many genes. The YPD-based control of asthma pathogenesis may be related to calcium ion (Ca2+) binding, inorganic cation transmembrane transporter activity, microtubule motor activity, and control of canonical signaling (e.g., peroxisome proliferator-activated receptor, calcium, cyclic adenosine monophosphate). Enrichment analyses suggested that asthma pathogenesis may be related to Ca2 + binding and contraction of vascular smooth muscle. A validation experiment showed that YPD could reduce the Ca2 + concentration by inhibiting the Angiopoietin-II (Ang-II)/Phospholipase (PLA)/calmodulin (CaM0 signaling axis., Conclusion: Control of asthma pathogenesis by YPD may be related to inhibition of the Ang-II/PLA/CaM signaling axis, reduction of the Ca 2+ concentration, and relaxation of airway smooth muscle (ASM)., (© 2024. The Author(s).)

Background and Aims: Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study., Methods: Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms., Results: Notably, THSWD induced a reduction in the neurological function score (P < 0.01) and neuronal injury in brain tissue, increase in protein expression of Claudin-5 and zonula occludens-1 (ZO-1) in brain tissue(P < 0.01), and decrease in serum lipopolysaccharide (LPS)(P < 0.01), diamine oxidase (DAO)(P < 0.01) and D-lactic acid(P < 0.01, P < 0.05) levels to a significant extent. THSWD also inhibited the levels of tumor necrosis factor-α (TNF-α)(P < 0.01) and interleukin - 1β (IL-1β)(P < 0.01) in brain tissue, and increased alpha and beta diversity in ischemic stroke mice, along with a certain reversal effect on different microflora. Finally, THSWD inhibited the polarization of microglia cells(P < 0.01) and decreased the protein and gene expression of toll-like receptor-4 (TLR-4)(P < 0.01, P < 0.05) and nuclear factor kappa B (NF-κB)(P < 0.01) in brain tissue., Conclusion: Our data indicate that THSWD may interfere with inflammatory response in ischemic stroke by regulating intestinal flora and promoting intestinal barrier repair., (© 2024. The Author(s).)

Background: To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP)., Methods: This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 10 9 /L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected., Results: A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 10 9 /L vs. 76.5 × 10 9 /L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 10 9 /L vs. 51.0 × 10 9 /L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories., Conclusion: SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate., (© 2024. The Author(s).)

Background: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors., Results: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses., Conclusions: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation., (© 2024. The Author(s).)

Psoriasis is an immune-mediated inflammatory skin disease, involving a complex interplay between genetic and environmental factors. Previous studies have demonstrated that genetic factors play a major role in the pathogenesis of psoriasis. However, non-genetic factors are also necessary to trigger the onset and recurrence of psoriasis in genetically predisposed individuals, which include infections, microbiota dysbiosis of the skin and gut, dysregulated lipid metabolism, dysregulated sex hormones, and mental illness. Psoriasis can also be induced by other environmental triggers, such as skin trauma, unhealthy lifestyles, and medications. Understanding how these triggers play a role in the onset and recurrence of psoriasis provides insights into psoriasis pathogenesis, as well as better clinical administration. In this review, we summarize the triggers for the onset and recurrence of psoriasis and update the current evidence on the underlying mechanism of how these factors elicit the disease. Video Abstract., (© 2024. The Author(s).)

Background: Characterizing cancer molecular subtypes is crucial for improving prognosis and individualized treatment. Integrative analysis of multi-omics data has become an important approach for disease subtyping, yielding better understanding of the complex biology. Current multi-omics integration tools and methods for cancer subtyping often suffer challenges of high computational efficiency as well as the problem of weight assignment on data types., Results: Here, we present an efficient multi-omics integration via weighted affinity and self-diffusion (MOSD) to dissect cancer heterogeneity. MOSD first construct local scaling affinity on each data type and then integrate all affinities by weighted linear combination, followed by the self-diffusion to further improve the patients' similarities for the downstream clustering analysis. To demonstrate the effectiveness and usefulness for cancer subtyping, we apply MOSD across ten cancer types with three measurements (Gene expression, DNA methylation, miRNA)., Conclusions: Our approach exhibits more significant differences in patient survival and computationally efficient benchmarking against several state-of-art integration methods and the identified molecular subtypes reveal strongly biological interpretability. The code as well as its implementation are available in GitHub: https://github.com/DXCODEE/MOSD ., (© 2024. The Author(s).)

Background: Cantharidin (CTD), the main toxic component of Mylabris, has been extensively used for tumor treatment in recent years. CTD-induced liver toxicity has attracted significant interest in clinic., Methods: In this study, biochemical parameters and liver pathological changes were analyzed after CTD was administered to mice by gavage. Subsequently, a lipidomic approach was used to investigate serum lipid metabolism disorders, and the mechanism underlying CTD-induced liver injury in mice was explored., Results: The results showed that the levels of TC and LDL-C were significantly increased after CTD intervention. Besides, pathological results showed inflammatory cell infiltration and hepatocyte necrosis in the liver. Furthermore, lipidomics found that a total of 18 lipid metabolites were increased and 40 were decreased, including LPC(20:4), LPC(20:3), PC(22:6e/2:0), PE(14:0e/21:2), PC(18:2e/22:6), glycerophospholipids, CE(16:0), CE(18:0) Cholesterol esters and TAG(12:0/12:0/22:3), TAG(16:1/16:2/20:4), TAG(18:1/18:1/20:0), TAG(16:2/18:2/18:2), TAG(18:0/18:0/20:0), TAG(13:1/19:0/19:0) glycerolipids. Metabolic pathway analysis found that glycerophospholipid, glycerol ester and glycosylphosphatidylinositol (GPI)-anchored biosynthetic metabolic pathways were dysregulated and the increase in PE caused by glycophoric metabololism and GPI may be the source of lipid metabolism disorders caused by CTD. Overall, the present study provided new insights into the mechanism of CTD-induced liver injury and increased drug safety during clinical application., (© 2024. The Author(s).)

Aims: Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, the underlying mechanism remains unclear. The role of vascular endothelial growth factor-B (VEGF-B) in DCM is little known. In present study, we aimed to investigate whether Mel alleviated DCM via regulation of VEGF-B and explored its underlying mechanisms., Methods and Results: We found that Mel significantly alleviated cardiac dysfunction and improved autophagy of cardiomyocytes in type 1 diabetes mellitus (T1DM) induced cardiomyopathy mice. VEGF-B was highly expressed in DCM mice in comparison with normal mice, and its expression was markedly reduced after Mel treatment. Mel treatment diminished the interaction of VEGF-B and Glucose-regulated protein 78 (GRP78) and reduced the interaction of GRP78 and protein kinase RNA -like ER kinase (PERK). Furthermore, Mel increased phosphorylation of PERK and eIF2α, then up-regulated the expression of ATF4. VEGF-B -/- mice imitated the effect of Mel on wild type diabetic mice. Interestingly, injection with Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration of GSK2656157 (GSK), an inhibitor of phosphorylated PERK abolished the protective effect of Mel on DCM. Furthermore, rapamycin, an autophagy agonist displayed similar effect with Mel treatment; while 3-Methyladenine (3-MA), an autophagy inhibitor neutralized the effect of Mel on high glucose-treated neonatal rat ventricular myocytes., Conclusions: These results demonstrated that Mel attenuated DCM via increasing autophagy of cardiomyocytes, and this cardio-protective effect of Mel was dependent on VEGF-B/GRP78/PERK signaling pathway., (© 2024. The Author(s).)