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Abstract Background To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. Methods Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. Results This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. Conclusion The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Abstract Plant-sucking insects have intricate associations with a diverse array of microorganisms to facilitate their adaptation to specific ecological niches. The midgut of phytophagous true bugs is generally structured into four distinct compartments to accommodate their microbiota. Nevertheless, there is limited understanding regarding the origins of these gut microbiomes, the mechanisms behind microbial community assembly, and the interactions between gut microbiomes and their insect hosts. In this study, we conducted a comprehensive survey of microbial communities within the midgut compartments of a bean bug Riptortus pedestris, soybean plant, and bulk soil across 12 distinct geographical fields in China, utilizing high-throughput sequencing of the 16 S rRNA gene. Our findings illuminated that gut microbiota of the plant-sucking insects predominantly originated from the surrounding soil environment, and plants also play a subordinate role in mediating microbial acquisition for the insects. Furthermore, our investigation suggested that the composition of the insect gut microbiome was probably shaped by host selection and/or microbe-microbe interactions at the gut compartment level, with marginal influence from soil and geographical factors. Additionally, we had unveiled a noteworthy dynamic in the acquisition of core bacterial taxa, particularly Burkholderia, which were initially sourced from the environment and subsequently enriched within the insect midgut compartments. This bacterial enrichment played a significant role in enhancing insect host reproduction. These findings contribute to our evolving understanding of microbiomes within the insect-plant-soil ecosystem, shedding additional light on the intricate interactions between insects and their microbiomes that underpin the ecological significance of microbial partnerships in host adaptation.

Abstract Background Leiomyosarcoma is a tumor that can develop in any organ that contains smooth muscles. Although leiomyosarcoma is common, its epididymal localization is quite rare. Case presentation A 79-year-old male Chinese Han patient presented with mild pain in the right groin and scrotum for 3 years concomitant with right scrotal swelling. Ultrasonography and magnetic resonance imaging of the scrotum showed a irregular and heterogeneous mass that was extratesticular. Right high orchiectomy was performed, and pathological examination of the resected specimen confirmed the diagnosis of leiomyosarcoma of the epididymis with surgical margins clear of tumor. Conclusion Epididymal leiomyosarcoma is rare and difficult to diagnose preoperatively. The final diagnosis of epididymal leiomyosarcoma requires histologic examination. Resection must be extensive and complete. The effect of chemotherapy and radiation on the epididymal leiomyosarcoma remains unclear. Recurrence is common, so follow-up is necessary.

Abstract Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein–protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.

Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.

Abstract Background With rapid urbanization, massive migration, and non-family–based eldercare involvement, Chinese concepts of eldercare responsibility and filial piety are shifting. We performed age-period-cohort (APC) analyses to assess the transition of old-age pension coverage, eldercare responsibility, and filial piety concepts and its urban-rural differences among Chinese adults using data from the China General Social Survey (2006–2017). Methods Old-age pension coverage (yes/no) and primary eldercare responsibility (government/offspring/self/sharing) were investigated in 2010, 2012, 2013, 2015, and 2017. Filial piety was evaluated using customized questionnaires in 2006 and 2017. The APC effects were estimated using mixed effects and generalized additive models. Results Among 66,182 eligible participants (mean age: 48.8 years, females: 51.7%) in the six waves, APC analyses indicated that old-age pension coverage increased with aging and over time. Across cohort groups, it grew as the cohort was younger in urban residents but decreased in rural residents. The concept of offspring-based (> 50%) and government/self/offspring-shared eldercare (> 30%) predominated. APC analyses revealed that the offspring-based concept declined with aging (OR = 0.81, 95% CI: 0.79–0.84), whereas the government-based (OR = 1.37, 95% CI: 1.33–1.41) and self-based (OR = 1.55, 95% CI: 1.47–1.63) concepts increased with aging. People born around the 1940s have a comparatively higher possibility to perceive that the primary eldercare responsibility should be undertaken by the government and elder parents. In contrast, people born in the younger cohort were more likely to perceive that adult children are responsible for their parents’ primary eldercare. Filial piety score slightly increased with aging (β = 0.18, SD: 0.05) but decreased as the birth cohort was younger. In addition, rural participants were more likely to perceive offspring-based eldercare and maintain filial piety, and the related urban-rural difference was intensified by aging. Conclusions The traditional concept that eldercare solely relies on offspring has changed to relying on multiple entities, including the government and self-reliance. Diluted filial piety in people born in the young cohort requires reinforcement. Moreover, future healthy aging policies need to focus more on urban-rural disparities to promote equity in social well-being.

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.

Most of the literature on reviewer assignment problem (RAP) considers fitness or efficiency as the evaluation criterion of an assignment, e.g., the degree of matching between reviewers and proposals. In this study, we consider fairness of an assignment and establish two multi-objective linear integer programming models for proposal assignment. We introduce a definition of fairness based on the closeness of social relationships between scholars. The closeness of social relationships is quantified based on social networks among reviewers and serves as part of objective functions. An improved space-partitioning algorithm is designed to solve the multi-objective models with integer objectives. When the problem size is large, two meta-heuristic algorithms are applied. Experiments on real and randomly generated cases are provided to illustrate the effectiveness of the proposed models and algorithms.

Abstract The directional transformation of carbon dioxide (CO2) with renewable hydrogen into specific carbon-heavy products (C6+) of high value presents a sustainable route for net-zero chemical manufacture. However, it is still challenging to simultaneously achieve high activity and selectivity due to the unbalanced CO2 hydrogenation and C–C coupling rates on complementary active sites in a bifunctional catalyst, thus causing unexpected secondary reaction. Here we report LaFeO3 perovskite-mediated directional tandem conversion of CO2 towards heavy aromatics with high CO2 conversion (> 60%), exceptional aromatics selectivity among hydrocarbons (> 85%), and no obvious deactivation for 1000 hours. This is enabled by disentangling the CO2 hydrogenation domain from the C-C coupling domain in the tandem system for Iron-based catalyst. Unlike other active Fe oxides showing wide hydrocarbon product distribution due to carbide formation, LaFeO3 by design is endowed with superior resistance to carburization, therefore inhibiting uncontrolled C–C coupling on oxide and isolating aromatics formation in the zeolite. In-situ spectroscopic evidence and theoretical calculations reveal an oxygenate-rich surface chemistry of LaFeO3, that easily escape from the oxide surface for further precise C–C coupling inside zeolites, thus steering CO2-HCOOH/H2CO-Aromatics reaction pathway to enable a high yield of aromatics.

Abstract The main objective was to establish a prognostic model utilising long non‐coding RNAs associated with disulfidptosis and cuproptosis. The data for RNA‐Sequence and clinicopathological information of Colon adenocarcinoma (COAD) were acquired from The Cancer Genome Atlas. A prognostic model was constructed using Cox regression and the Least Absolute Shrinkage and Selection Operator method. The model's predictive ability was assessed through principal component analysis, Kaplan–Meier analysis, nomogram etc. The ability of identifying the rates of overall survival, infiltration of immune cells, and chemosensitivity was also explored. In vitro experiments were conducted for the validation of differential expression and function of lncRNAs. A disulfidptosis and cuproptosis‐related lncRNA prognostic model was constructed. The prognostic model exhibits excellent independent predictive capability for patient outcomes. Based on the authors’ model, the high‐risk group exhibited higher tumour mutation burdened worse survival. Besides, differences in immune cell infiltration and responsiveness to chemotherapeutic medications exist among patients with different risk scores. Furthermore, aberrant expressions in certain lncRNAs have been validated in HCT116 cells. In particular, FENDRR and SNHG7 could affect the proliferation and migration of colorectal cancer cells. Our study developed a novel prognostic signature, providing valuable insights into prognosis, immune infiltration, and chemosensitivity in COAD patients.

Abstract Background Based on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI). Methods We included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer’s disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration. Results The clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL. Conclusions Our finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

Abstract Background and purpose The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). Materials and methods This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7–14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. Results No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7–14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045). Conclusion Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.

An efficient alkoxyl radical-triggered ring expansion/cross-coupling cascade was developed under cheap metal catalysis. Through the metal-catalyzed radical relay strategy, a wide range of medium-sized lactones (9-11 membered) and macrolactones (12, 13, 15, 18, and 19-membered) were constructed in moderate to good yields, along with diverse functional groups including CN, N3, SCN, and X groups installed concurrently. Density functional theory (DFT) calculations revealed that reductive elimination of the cycloalkyl-Cu(iii) species is a more favorable reaction pathway for the cross-coupling step. Based on the results of experiments and DFT, a Cu(i)/Cu(ii)/Cu(iii) catalytic cycle is proposed for this tandem reaction.

Background: Coronary heart disease (CHD) is the most common cardiovascular disease facing human beings. Cardiac remodelling is an important pathological factor for the progression of heart failure (HF) after CHD. At present, Chinese medicine is widely used in the treatment of HF, but there are still some drugs lack of evidence-based and mechanism evidence. Multi-omics techniques can deep explore candidate pathogenic factors and construct gene regulatory networks.This trial is intended to evaluate the effect on Huoxin pill (HXP) in the treatment of HF after programmable communication interface (PCI). Meantime, multi-omics analysis technique will be used to target the fundamental pathological links of cardiac remodelling, so as to study the mechanism of HXP in the treatment of HF after PCI. Methods: This study is a randomized, double-blind, placebo-controlled trial. Sixty patients with HF undergoing PCI are recruited from the First Affiliated Hospital of Henan University of CM. All selected patients will be randomly attributed to receive conventional treatment + HXP or placebo. The packaging, dosage and smell of placebo and heart activating pill were identical. The primary outcome is NYHA cardiac function grade, while the secondary outcomes included Lee's HF score, exercise tolerance test, and quality of life evaluation. Additional indicators include cardiac ultrasound, electrocardiogram, 24-h dynamic electrocardiogram, myocardial injury indicators, and energy metabolism indicators. Discussion: This study may provide a new treatment option for patients with HF after PCI and provide evidence for the treatment of CHD and HF with HXP. Trial registration: 2023-10-08 registered in China Clinical Trial Registry, registration number ChiCTR2300076402.

Abstract BackgroundEarly identification of impending in-hospital cardiac arrest (IHCA) improves clinical outcomes but remains elusive for practicing clinicians. ObjectiveWe aimed to develop a multimodal machine learning algorithm based on ensemble techniques to predict the occurrence of IHCA. MethodsOur model was developed by the Multiparameter Intelligent Monitoring of Intensive Care (MIMIC)–IV database and validated in the Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Baseline features consisting of patient demographics, presenting illness, and comorbidities were collected to train a random forest model. Next, vital signs were extracted to train a long short-term memory model. A support vector machine algorithm then stacked the results to form the final prediction model. ResultsOf 23,909 patients in the MIMIC-IV database and 10,049 patients in the eICU-CRD database, 452 and 85 patients, respectively, had IHCA. At 13 hours in advance of an IHCA event, our algorithm had already demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI 0.815‐0.885) in the MIMIC-IV database. External validation with the eICU-CRD and National Taiwan University Hospital databases also presented satisfactory results, showing area under the receiver operating characteristic curve values of 0.81 (95% CI 0.763-0.851) and 0.945 (95% CI 0.934-0.956), respectively. ConclusionsUsing only vital signs and information available in the electronic medical record, our model demonstrates it is possible to detect a trajectory of clinical deterioration up to 13 hours in advance. This predictive tool, which has undergone external validation, could forewarn and help clinicians identify patients in need of assessment to improve their overall prognosis.