Identification of potential immune-related mechanisms related to the development of multiple myeloma.

BACKGROUND: Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. METHODS: This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. RESULTS: A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG + Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don't eat me"-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. CONCLUSIONS: Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Involving logical clinical knowledge into deep neural networks to improve bladder tumor segmentation.

Segmentation of bladder tumors from medical radiographic images is of great significance for early detection, diagnosis and prognosis evaluation of bladder cancer. Deep Convolution Neural Networks (DCNNs) have been successfully used for bladder tumor segmentation, but the segmentation based on DCNN is data-hungry for model training and ignores clinical knowledge. From the clinical view, bladder tumors originate from the mucosal surface of bladder and must rely on the bladder wall to survive and grow. This clinical knowledge of tumor location is helpful to improve the bladder tumor segmentation. To achieve this, we propose a novel bladder tumor segmentation method, which incorporates the clinical logic rules of bladder tumor and bladder wall into DCNNs to harness the tumor segmentation. Clinical logical rules provide a semantic and human-readable knowledge representation and are easy for knowledge acquisition from clinicians. In addition, incorporating logical rules of clinical knowledge helps to reduce the data dependency of the segmentation network, and enables precise segmentation results even with limited number of annotated images. Experiments on bladder MR images collected from the collaborating hospital validate the effectiveness of the proposed bladder tumor segmentation method.

Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Scoping review of obesity interventions: Research frontiers and publication status.

Obesity and overweight are significant global health issues, and numerous obesity intervention studies have been conducted. Summarizing current knowledge of interventions aims to inform researchers and policymakers to keep up-to-date with the latest scientific advancements and trends. In this review, we comprehensively retrieved and screened 4,541 studies on obesity intervention published between 2018 and 2022 in the Web of Science Core Collection, and objectively presented research frontiers using bibliometric analysis. The research frontiers of intervention are mainly focused on dietary, exercise, pharmacological interventions, bariatric surgery, environmental, and cognitive interventions. Time-restricted eating is the hottest research topic, followed by probiotics and Roux-en-Y gastric bypass. Gut microbiota is located in the "Basic and transversal themes" quadrant with a high centrality and low density, which has great development potentiality. Obesity intervention is becoming increasingly common,and we advocate for researchers to undertake more focused research endeavors that consider the specific characteristics of diverse populations or patients.

Cysteine- and glycine-rich protein 1 predicts prognosis and therapy response in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein-protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

Blocking cerebral lymphatic system reduces central and peripheral inflammatory response in ischemic stroke.

Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics' role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4+ T lymphocytes, CD8+ T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1ß, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

Safety and effcacy of remimazolam tosilate for sedation during combined spinal-epidural anesthesia for orthopedic procedures: a randomized controlled trial.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of Remimazolam in the context of combined spinal-epidural anesthesia for sedation during orthopedic surgery. METHODS: This randomized controlled trial enrolled patients scheduled for orthopedic surgery under combined spinal-epidural anesthesia (N = 80), who were randomly allocated to receive either dexmedetomidine (Group-D) or remimazolam (Group-R). The target sedation range aimed for a Ramsay score of 2-5 or a BIS value of 60-80 to evaluate the effectiveness and safety of remimazolam during sedation. RESULTS: The time taken to achieve the desired level of sedation was significantly shorter in the remimazolam group compared to the dexmedetomidine group (3.69 ± 0.75 vs. 9.59 ± 1.03; P < 0.0001). Patients in the remimazolam group exhibited quicker recovery, fewer intraoperative adverse events, more consistent vital signs, and greater satisfaction at various time points throughout the surgery. CONCLUSION: This preliminary study demonstrates that remimazolam tosilate serves as a safe and effective sedative for orthopedic surgery performed under combined spinal-epidural anesthesia, in comparison with dexmedetomidine.

pH-sensitive dual-preventive siRNA-based nanomicrobicide reactivates autophagy and inhibits HIV infection in vaginal CD4+ cells.

Women are more susceptible to HIV transmission through unprotected heterosexual intercourse due to biological and social vulnerabilities. Intravaginal delivery of siRNAs targeting viral genes, host genes, or in combination has shown promising outcomes against HSV, HPV and HIV. Therefore, in this study, we designed, developed and evaluated a pH-sensitive RNAi-based combination nanomicrobide for the prevention/reduction of vaginal transmission of HIV. The nanomicrobide was composed of siRNA-PEI encapsulated PLGA-PEG nanoparticles (siRNA NP) loaded in a HEC gel dosage form with siRNA targeting host gene CCR5 and the viral gene Nef as a dual preventive strategy. Knocking down CCR5, a co-receptor for HIV could prevent HIV from attaching to and entering host cells and knocking down Nef could reactivate autophagy that was inhibited by Nef to improve the elimination of intracellular virus that escaped the first line of defense. The siRNA NP showed a desirable particle size and zeta potential for intravaginal delivery and a pH-dependent release profile whereby low amounts of siRNA was released under acidic vaginal conditions (vaginal fluid simulant; VFS, pH 4.2) (6.0 ± 0.4% released over 15 days) but significantly higher amounts of siRNA was released under neutral pH conditions (phosphate buffered saline; PBS, pH 7.4) (22.9 ± 0.4% released over 15 days). The CCR5-Nef-specific siRNA NP efficiently knocked down CCR5 and Nef protein expression by 43% and 63%, respectively, reactivated Nef-blocked autophagy and inhibited the replication of HIV in vitro (71.8% reduction in p24 expression). After being formulated into a gel dosage form, siRNA NP could be readily released from the gel, penetrate the vaginal epithelial layer, get taken up into the target cells and knockdown Nef and CCR5 without causing cytotoxicity in a vaginal mucosal co-culture model. Functionalization of siRNA NP with anti-CD4 antibody and loaded into a 0.5% HEC gel improved vaginal distribution and uptake of siRNA in a mouse model with distribution of siRNA restricted to the reproductive tract without any unwanted systemic uptake. The 0.5% HEC gel loaded with siRNA NP-(m)CD4 significantly downregulated approximately 40% of CCR5 protein in the lower vagina and 36% of CCR5 protein in the upper vaginal and cervical region. In contrast, 0.5% HEC gel loaded with siRNA NP-IgG did not result in significant gene knockdown.

Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer.

Cancer stem cells (CSCs) are the most intractable subpopulation of triple-negative breast cancer (TNBC) cells, which have been associated with a high risk of relapse and poor prognosis. However, eradication of CSCs continues to be difficult. Here, we integrate the multiomics data of a TNBC cohort (n = 360) to identify vital markers of CSCs. We discover that EMSY, inducing a BRCAness phenotype, is preferentially expressed in breast CSCs, promotes ALDH+ cells enrichment, and is positively correlated with poor relapse-free survival. Mechanistically, EMSY competitively binds to the Jmjc domain, which is critical for KDM5B enzyme activity, to reshape methionine metabolism, and to promote CSC self-renewal and tumorigenesis in an H3K4 methylation-dependent manner. Moreover, EMSY accumulation in TNBC cells sensitizes them to PARP inhibitors against bulk cells and methionine deprivation against CSCs. These findings indicate that clinically relevant eradication of CSCs could be achieved with a strategy that targets CSC-specific vulnerabilities in amino acid metabolism.

Automated pancreatic segmentation and fat fraction evaluation based on a self-supervised transfer learning network.

Accurate segmentation of the pancreas from abdominal computed tomography (CT) images is challenging but essential for the diagnosis and treatment of pancreatic disorders such as tumours and diabetes. In this study, a dataset with 229 sets of high-resolution CT images was generated and annotated. We proposed a novel 3D segmentation model named nnTransfer (nonisomorphic transfer learning) net, which employs generative model structure for self-supervision to facilitate the network's learning of image attributes from unlabelled data. The effectiveness for pancreas segmentation of nnTransfer was assessed using the Hausdorff distance (HD) and Dice similarity coefficient (DSC) on the dataset. Additionally, a histogram analysis with local thresholding was used to achieve automated whole-volume measurement of pancreatic fat (fat volume fraction, FVF). The proposed technique performed admirably on the dataset, with DSC: 0.937 ± 0.019 and HD: 2.655 ± 1.479. The mean pancreas volume and FVF of the pancreas were 91.95 ± 23.90 cm3 and 12.67 % ± 9.84 %, respectively. The nnTransfer functioned flawlessly and autonomously, facilitating the use of the FVF to evaluate pancreatic disease, particularly in patients with diabetes.

Return to flight duty (RTFD) after posterior lumbar spine surgery for symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) in Chinese military pilots.

BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.

Identification of arnicolide C as a novel chemosensitizer to suppress mTOR/E2F1/FANCD2 axis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.

Association of iron status with all-cause and cause-specific mortality in individuals with diabetes.

AIMS: Current evidence regarding iron status and mortality risk among patients with diabetes is limited. This study aimed to evaluate association of iron indices with all-cause and cause-specific mortality risk among patients with diabetes. METHODS: The current study included 2080 (with ferritin data), 1974 (with transferrin saturation (Tsat) data), and 1106 (with soluble transferrin receptor (sTfR) data) adults with diabetes from NHANES 1999-2018. Death outcomes were obtained from National Death Index through December 31, 2019. Cox proportional hazards models were employed to calculate hazard ratios and 95% confidence intervals for mortality. RESULTS: Association with all-cause mortality was demonstrated to be J-shaped for serum ferritin (Pnonlinearity < 0.01), U-shaped for Tsat (Pnonlinearity < 0.01) and linear for sTfR (Plinearity < 0.01). Ferritin 300-500 ng/mL possessed lower all-cause mortality risk than ferritin ≤ 100 ng/mL, 100-300 ng/mL, and > 500 ng/mL. Tsat 25-32 % showed a protective effect on all-cause mortality risk compared with Tsat ≤ 20 %, 20-25 %, and > 32 %. Individuals with sTfR < 4 mg/L were associated with a lower risk of all-cause mortality than those with higher sTfR. CONCLUSIONS: Moderate levels of serum ferritin (300-500 ng/mL), Tsat (25 %-32 %) and a lower concentration of sTfR (< 4 mg/L) identified adults with diabetes with lower all-cause mortality risk, adding novel modifiers to diabetes management.

Neutrophil-to-serum iron ratio as a promising inflammatory biomarker for acute myocardial infarction and Gensini score.

Background: We aim to investigate whether the neutrophil-to-serum iron ratio (N/SI) is a promising biomarker for acute myocardial infarction group (AMI) and Gensini score. Methods: A total of 263 patients were enrolled and divided into four groups. The Gensini score was used to gauge the severity of coronary artery stenosis, and inflammatory biomarkers were calculated. Results: The N/SI was substantially higher in the AMI group than those in other groups, and N/SI was an independent risk factor for AMI. In ROC analyses, N/SI had the highest area under curve (AUC) for AMI among those inflammatory biomarkers. N/SI was also proved to be related with Gensini score. Conclusion: N/SI was discovered to be a new and effective inflammatory biomarker for AMI and Gensini score.

Peoples' health is at risk from heart illnesses. The indicators in patients' blood are often used to evaluate the severity of diseases. The authors collected 263 subjects with heart disease and reviewed their clinical data. Their blood was drawn to measure the neutrophil-to-serum iron ratio, a crucial blood biomarker. In conclusion, the level of neutrophil-to-serum iron ratio in these patients was closely associated with the stage and severity of their disease.

Multiomics of HER2-low triple-negative breast cancer identifies a receptor tyrosine kinase-relevant subgroup with therapeutic prospects.

To provide complementary information and reveal the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multiomics study of hormone receptor-negative (HR-) and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified 3 subgroups: basal-like, receptor tyrosine kinase-relevant (TKR), and mesenchymal stem-like. These 3 subgroups had distinct features and potential therapeutic targets and were validated in external data sets. Interestingly, the TKR subgroup (which exists in both HR+ and HR- breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment of the TKR subgroup with a tyrosine kinase inhibitor (lapatinib or tucatinib) could inhibit HER2 signaling and induce accumulated expression of nonfunctional HER2, resulting in increased sensitivity to the sequential HER2-targeting, Ab-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes.

Fecal short chain fatty acids modify therapeutic effects of sleeve gastrectomy.

Aims: We aimed to investigate changes of fecal short chain fatty acids (SCFAs) and their association with metabolic benefits after sleeve gastrectomy (SG). Specifically, whether pre-surgery SCFAs modify surgical therapeutic effects was determined. Methods: 62 participants with measurements of fecal SCFAs and metabolic indices before and 1, 3, 6 months after SG were included. Changes of fecal SCFAs and their association with post-surgery metabolic benefits were calculated. Then, participants were stratified by medians of pre-surgery fecal SCFAs and modification effects of pre-surgery fecal SCFAs on surgical therapeutic effects were investigated, through calculating interaction of group by surgery. Results: Fecal SCFAs were markedly changed by SG. Changes of propionate and acetate were positively correlated with serum triglycerides and total cholesterol, respectively. Notably, high pre-surgery fecal hexanoate group showed a better effect of SG treatment on lowering body weight (P=0.01), BMI (P=0.041) and serum triglycerides (P=0.031), and low pre-surgery fecal butyrate had a better effect of SG on lowering ALT (P=0.003) and AST (P=0.019). Conclusion: Fecal SCFAs were changed and correlated with lipid profiles improvement after SG. Pre-surgery fecal hexanoate and butyrate were potential modifiers impacting metabolic benefits of SG.

Return to active duty after anterior cruciate ligament reconstruction (ACLR) in Chinese male military aircrews.

Background: Surgically treated anterior cruciate ligament (ACL) injuries may be a waivable condition and allow return to full flight status, but waivers are based on expert opinion rather than recent published data. The purpose of this study was to evaluate return to flight after anterior cruciate ligament reconstruction (ACLR) in male military aircrews with ACL injuries and to identify factors that affect flight clearance. Method: A single-center retrospective review was conducted by the authors for all active-duty aircrew who underwent ACLR at an authorized military medical center from January 2010 to December 2019. Demographic characteristics, occupational information, surgical data, and flight readiness evaluation outcomes were collected. Based on the final medical evaluation, subjects were divided into a qualified group (N = 64) and a disqualified group (N = 9), and the difference in data collected between the two groups was then analyzed to identify factors affecting flight clearance. Results: A total of 73 patients underwent successful ACLR with a mean age of 31.6 ± 5.6 years. Non-contact injury was the main type of ACL injury, accounting for 84.9% of the total injuries. 55 cases (75.3%) occurred during daily sports activities and 18 (24.7%) during military training. 64 of the 73 crewmembers (87.7%) were able to return to flight at their last follow-up evaluation. The preoperative interval time (PIT) was significantly less in the qualified group than in the disqualified group (P = 0.002). Patients who underwent ACLR within three months were more likely to return to flying than those who underwent the procedure three months later (97.4% vs. 76.5%, P = 0.010). The incidence of failure to return to flight duty was significantly higher in aircrews with ACL injuries combined with meniscal injuries than in aircrews with isolated ACL injuries (21.4% vs. 0.0%, P = 0.017). Conclusion: ACLR appears to be safe for military aircrew suffering ACL injuries with or without meniscal injury, and return to flight status is the most likely outcome for the majority of postoperative pilots. Prolonged PIT, PIT > 3 months, and ACL injury combined with meniscus injury had a negative impact on postoperative flight readiness.

Bioinspired hierarchical colloidal crystal paper with Janus wettability for oil/water separation and heavy metal ion removal.

Increasing attention has been paid recently to superwettability and its prospective potential applications in various fields. A new approach towards the establishment of flexible, self-assembled superhydrophobic surfaces with self-reported wettability on a variety of substrates has been advanced. The approach involves the fabrication of a dense monolayer of photonic crystal films that possess a layered structure with superior adhesion at the liquid-gas-solid interface. Thus, the resulting hierarchical photonic crystal film with a structurally hydrophobic surface offers a promising addition to the creation of durable and flexible superhydrophobic surfaces across a variety of substrates that exhibit the self-reported wettability. Furthermore, a bifunctional membrane that can effectively remove oil and adsorb heavy metal ions contained in wastewater has been developed for potential use in large-scale industrial wastewater treatment. This research sheds fresh light on the application of bionics and the lotus and mussel functions in oil/water separation.

Connecting the Dots: N6-Methyladenosine (m6 A) Modification in Spermatogenesis.

N6-methyladenosine (m6 A) is the most common RNA modification found in eukaryotes and is involved in multiple biological processes, including neuronal development, tumorigenesis, and gametogenesis. It is well known that methylation-modifying enzymes (classified into writers, erasers, and readers) mediate catalysis, clearance, and recognition of m6 A. Recent studies suggest that these genes may be associated with spermatogenesis. Numerous studies have revealed the m6 A role during spermatogenesis. However, the expression patterns and relationships of these m6 A enzymes during various stages of spermatogenesis remain unknown. In this review, it is aimed to provide an overview of m6 A enzyme functions and elucidate their potential mechanisms and regulatory relationships at a specific phase during spermatogenesis, providing new insights into the m6 A modification underlying the spermatogenesis process.

MALAT1 binds to miR-188-3p to regulate ALOX5 activity in the lung inflammatory response of neonatal bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) causes high morbidity and mortality in infants, but no effective preventive or therapeutic agents have been developed to combat BPD. In this study, we assessed the expression of MALAT1 and ALOX5 in peripheral blood mononuclear cells from BPD neonates, hyperoxia-induced rat models and lung epithelial cell lines. Interestingly, we found upregulated expression of MALAT1 and ALOX5 in the experimental groups, along with upregulated expression of proinflammatory cytokines. According to bioinformatics prediction, MALAT1 and ALOX5 simultaneously bind to miR-188-3p, which was downregulated in the experimental groups above. Silencing MALAT1 or ALOX5 and overexpressing miR-188-3p inhibited apoptosis and promoted the proliferation of hyperoxia-treated A549 cells. Suppressing MALAT1 or overexpressing miR-188-3p increased the expression levels of miR-188-3p but decreased the expression levels of ALOX5. Moreover, RNA immunoprecipitation (RIP) and luciferase assays showed that MALAT1 directly targeted miR-188-3p to regulate ALOX5 expression in BPD neonates. Collectively, our study demonstrates that MALAT1 regulates ALOX5 expression by binding to miR-188-3p, providing novel insights into potential therapeutics for BPD treatment.