CG9920 is necessary for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster.

Drosophila melanogaster is an ideal model organism for investigating spermatogenesis due to its powerful genetics, conserved genes and visible morphology of germ cells during sperm production. Our previous work revealed that ocnus (ocn) knockdown resulted in male sterility, and CG9920 was identified as a significantly downregulated protein in fly abdomen after ocn knockdown, suggesting a role of CG9920 in male reproduction. In this study, we found that CG9920 was highly expressed in fly testes. CG9920 knockdown in fly testes caused male infertility with no mature sperms in seminal vesicles. Immunofluorescence staining showed that depletion of CG9920 resulted in scattered spermatid nuclear bundles, fewer elongation cones that did not migrate to the anterior region of the testis, and almost no individualization complexes. Transmission electron microscopy revealed that CG9920 knockdown severely disrupted mitochondrial morphogenesis during spermatogenesis. Notably, we found that CG9920 might not directly interact with Ocn, but rather was inhibited by STAT92E, which itself was indirectly affected by Ocn. We propose a possible novel pathway essential for spermatogenesis in D. melanogaster, whereby Ocn indirectly induces CG9920 expression, potentially counteracting its inhibition by the JAK-STAT signaling pathway.

Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1- NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.

Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification.

BACKGROUND AND AIMS: Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. METHODS: In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. RESULTS: Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10-5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10-5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). CONCLUSIONS: Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.

Wavelength-Resolved Janus Biosensing Interface for Ratiometric Electrochemical Analysis.

The Janus interface, comprising multiple functional heterointerfaces with contrasting functionalities within a single interface, has recently garnered widespread research interest. Herein, a Janus biosensing interface is obtained via wavelength-resolved laser illumination. Deoxyribonucleic acid bridges the electrochemical probe of methylene blue (MB) and plasmonic gold nanoparticles (AuNPs), achieving a sensitive detection performance. MB shows differential electrochemical signals under front (I532front) and back (I650back) laser illumination at 532 and 650 nm, respectively, owing to the selective wavelength-resolved effect. Thus, the presence of a wavelength-resolved laser enabled the design of a biosensing interface with Janus properties. The change in the distance between MB and AuNPs induced by aflatoxin B1 (AFB1) indicates that a sensitive response of the Janus biosensing interface can be achieved. A ratiometric strategy is introduced to describe the electrochemical signals of the I532front and I650back for improved robustness. The obtained linear range is 0.0005-50 ng mL-1, with a detection limit of 0.175 pg mL-1. Our study demonstrated that the wavelength-resolved Janus interface enables an electrochemical biosensor with excellent sensitivity. This finding provides an efficient approach for improving biosensor performance.

Reducing Eosinophil Counts in Eosinophilic Esophagitis in Children Is Associated With Reduction in Later Stricture Development.

INTRODUCTION: There are limited longitudinal data on the impact of chronic therapy on the natural history of eosinophilic esophagitis (EoE), a chronic allergic disease of the esophagus. The purpose of this study was to evaluate if patients with well-controlled EoE were less likely to develop fibrostenotic complications. METHODS: Subjects were identified from a database of pediatric patients with EoE at the Children's Hospital of Philadelphia started in 2000. Patients were then searched in adult medical records to identify patients who transitioned care. All office visits, emergency department visits, and endoscopic, histologic, and imaging reports were reviewed for the primary outcome of strictures and the secondary outcomes of food impactions and dysphagia. Cox proportional hazard regression was performed for outcomes. RESULTS: One hundred five patients were identified with the mean follow-up of 11.4 ± 4.9 years. 52.3% (n = 55) had a period of histologic disease control defined as ≥2 consecutive endoscopies with histologic remission. These patients were less likely to develop strictures compared with patients who did not have a period of histologic control (HR 0.232; 95% CI 0.084-0.64, P = 0.005). Patients who were diagnosed at younger ages were less likely to develop strictures. Presentation with dysphagia or impaction was associated with higher rate of stricture development. DISCUSSION: In this cohort study with > 10 years of follow-up, children with EoE with a period of histologic disease control and diagnosed at younger ages were less likely to develop esophageal strictures. While this suggests histologic remission is associated with reduction of remodeling complications, additional prospective data with long-term follow-up are needed.

Longitudinal, natural history study reveals the disease burden of idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with heterogeneous presentations ranging from moderate constitutional symptoms to life-threatening multiorgan system involvement. There are vastly different clinical subtypes, with some patients demonstrating thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin fibrosis/renal failure, and organomegaly (TAFRO) and others having milder/more moderate symptoms with potential for severe disease (not otherwise specified, NOS). Due to its rarity and heterogeneity, the natural history and long-term burden of iMCD are poorly understood. We investigated real-world medical data from ACCELERATE, a large natural history registry of patients with Castleman disease, to better characterize the long-term disease burden experienced by these patients. We found that iMCD-TAFRO patients face a significant hospitalization burden, requiring more time in the hospital than iMCDNOS patients during the year surrounding diagnosis (median [interquartile range]: 36 [18-61] days vs. 0 [0-4] days; P<0.001). In addition, we found life-sustaining interventions, such as mechanical ventilation (17%) and dialysis (27%), were required among iMCD patients, predominantly those with iMCD-TAFRO. iMCD-NOS patients, however, spent a significantly greater proportion of time following disease onset in a state of disease flare (median 52.3% vs. 18.9%; P=0.004). Lastly, we observed severe iMCD-related morbidities, such as acute renal failure, sepsis and pneumonia, among others, arising after iMCD diagnosis, impairing the patients' quality of life. These data demonstrate a substantial disease burden experienced by iMCD patients and emphasize the importance of ongoing research into iMCD to aid disease control.

Introgression and incomplete lineage sorting blurred phylogenetic relationships across the genomes of sclerophyllous oaks from southwest China.

Resolving evolutionary relationships among closely related species with interspecific gene flow is challenging. Genome-scale data provide opportunities to clarify complex evolutionary relationships in closely related species and to observe variations in species relationships across the genomes of such species. The Himalayan-Hengduan subalpine oaks have a nearly completely sympatric distribution in southwest China and probably constitute a syngameon. In this study, we mapped resequencing data from different species in this group to the Quercus aquifolioides reference genome to obtain a high-quality filtered single nucleotide polymorphism (SNP) dataset. We also assembled their plastomes. We reconstructed their phylogenetic relationships, explored the level and pattern of introgression among these species and investigated gene tree variation in the genomes of these species using sliding windows. The same or closely related plastomes were found to be shared extensively among different species within a specific geographical area. Phylogenomic analyses of genome-wide SNP data found that most oaks in the Himalayan-Hengduan subalpine clade showed genetic coherence, but several species were found to be connected by introgression. The gene trees obtained using sliding windows showed that the phylogenetic relationships in the genomes of oaks are highly heterogeneous and therefore highly obscured. Our study found that all the oaks of the Himalayan-Hengduan subalpine clade from southwest China form a syngameon. The obscured phylogenetic relationships observed empirically across the genome are best explained by interspecific gene flow in conjunction with incomplete lineage sorting.

Effects of carbon emission trading system on corporate green total factor productivity: Does environmental regulation play a role of green blessing?

Extant studies focus on the impact of environmental regulation on regional economic growth or environmental pollution, and a lot of research outcomes have been made. However, from the perspective of corporate green sustainable development, the question of whether carbon emission trading represents a "green blessing" remains unclear. To address this issue, we employ a staggered difference-in-differences model to investigate the effects and mechanisms of the carbon emissions trading pilot policy (CETPP) on the green total factor productivity (GTFP) of listed manufacturing companies in China. Our results demonstrate that: a) CETPP can effectively promote corporate GTFP, and the robustness of this result is verified through a series of checks; b) the mediating role of environmental, social, and governance (ESG) performance is critical in the relationship between CETPP and corporate GTFP, with environmental and governance performance serving as two key transmission channels; and c) CEO green experience and public environmental concern both play the moderating roles on the relationship between CETPP and GTFP; d) CETPP has a stronger positive impact on GTFP of private enterprises and enterprises in the maturity life cycle; and e) CETPP has a spatial spillover effect on GTFP, and the effect will decay as spatial distance increases. Our study offers both theoretical and practical implications for enterprises to achieve their green economic development objectives, so as to promote China's high-quality development.

Altered brain function and structure pre- and post- COVID-19 infection: a longitudinal study.

BACKGROUND: Evidence indicates that the SARS-CoV-2 virus can infect the brain, resulting in central nervous system symptoms. However, there is a lack of a longitudinal imaging study investigating the impact of Coronavirus disease 2019 (COVID-19) infection on brain function. Consequently, this study aimed to fill this knowledge gap using functional magnetic resonance imaging (fMRI). METHODS: Twenty-one participants underwent two resting-state fMRI scans before and after infection. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were assessed to identify the brain function changes. Additionally, voxel-based morphometry (VBM) was utilized to assess changes in brain structure. Subsequently, brain regions that showed significant differences were identified as regions of interest (ROI) in functional connectivity analysis (FC). RESULTS: After infection, ALFF was increased in the bilateral paracentral lobe and postcentral gyrus while decreased in the bilateral precuneus. Moreover, ReHo was decreased in the cerebellar vermis, accompanied by a decrease in FC with the bilateral postcentral gyrus. Furthermore, gray matter volume (GMV) reduction was observed in the left thalamus. The results of the correlation analysis revealed a negative correlation between ALFF values in the bilateral precuneus and scores on the self-rating anxiety scale (SAS) in pre- and post-infection datasets. CONCLUSION: Neuroimaging alterations may occur before the manifestation of clinical symptoms, indicating that the functioning of the motor and sensory systems, as well as their connection, might be affected following infection. This alteration can potentially increase the potential of maladaptive responses to environmental stimuli. Furthermore, patients may be susceptible to future emotional disorders.

Effects of forages on the microbiota of crossed sheep on cold Plateau.

Diet is an important component to influence microbiota, there are less data available about the microbiome of Suffolk cross with Tibetan (SCT) animals with different fodders. The current study was conducted for comparing the fungi microbiota in SCT sheep fed with different forages. Sequencing of ileum samples from sheep groups of AH (alfalfa and oat grass), BH (mixture of grass and concentrated feeds), CH (concentrated feed I), DH (concentrated feed II) and EH (concentrated feed III) achieved 3,171,271 raw and 2,719,649 filtered sequences. Concentrated feeds changed fungi microbiota in SCT sheep with three phyla and 47 genera significantly different among the groups. Genera include positive genus of Scytalidium and negative fungi of Sarocladium, Kazachstania, Gibberella, Scytalidium, Candida, Wickerhamomyces. The findings of our study will contribute to efficient feeding of SCT sheep at cold plateau areas.

Proteomic cardiovascular risk assessment in chronic kidney disease.

AIMS: Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models. METHODS AND RESULTS: Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when ∼5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis. CONCLUSION: In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population.

Anaesthesia management of interventional cardiac catheterisation for pulmonary atresia with intact ventricular septum and critical pulmonary stenosis: a retrospective analysis.

OBJECTIVE: Pulmonary atresia with intact ventricular septum and critical pulmonary stenosis usually have to undergo treatment in the neonatal period. Compared to traditional surgical intervention, catheter-based cardiac interventions may achieve similar or superior outcomes for neonates with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. However, there is limited literature on anaesthesia techniques, challenges, and risks associated with cardiac catheterisation in this population. METHODS: This article retrospectively analysed the clinical data of pulmonary atresia with intact ventricular septum and critical pulmonary stenosis neonates who were treated with interventional cardiac catheterisation in our hospital from January 2015 to October 2022. Clinical outcomes considered were haemodynamic or pulse oxygen saturation instability, vasoactive requirements, prolonged intubation (>24 h postoperatively), and cardiovascular adverse events. RESULTS: A total of 63 patients met the inclusion criteria. All patients survived the intervention. Among the patients with critical pulmonary stenosis, 40 successfully received percutaneous balloon pulmonary valvuloplasty, while three patients received ductal stenting due to moderate right ventricular dysplasia at the same time. For patients with pulmonary atresia with intact ventricular septum, 17 of the 23 patients successfully underwent percutaneous pulmonary valve perforation and percutaneous balloon pulmonary valvuloplasty. Of these, five patients underwent ductal stenting due to unstable pulmonary blood flow. Three patients only underwent ductal stenting. In addition, three patients received hybrid therapy. CONCLUSIONS: There are various clinical techniques and risk challenges in the interventional cardiac catheterisation of neonatal pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. However, by mastering the physiological and pathophysiological characteristics of the disease, adequately preparing for the perioperative period, and predicting the procedure process and potential complications, anaesthesia and surgical risks can be effectively managed.

Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel.

Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca2+-gated ATP channel that plays an important role in neuronal signaling. However, as the previously reported CALHM structures are all in the ATP-conducting state, the gating mechanism of ATP permeation is still elusive. Here, we report cryo-EM reconstructions of two Danio rerio CALHM1 heptamers with ordered or flexible long C-terminal helices at resolutions of 3.2 Å and 2.9 Å, respectively, and one D. rerio CALHM1 octamer with flexible long C-terminal helices at a resolution of 3.5 Å. Structural analysis shows that the heptameric CALHM1s are in an ATP-nonconducting state with a central pore diameter of approximately 6.6 Å. Compared with those inside the octameric CALHM1, the N-helix inside the heptameric CALHM1 is in the "down" position to avoid steric clashing with the adjacent TM1 helix. Molecular dynamics simulations show that as the N-helix moves from the "down" position to the "up" position, the pore size of ATP molecule permeation increases significantly. Our results provide important information for elucidating the mechanism of ATP molecule permeation in the CALHM1 channel.

Electrocatalytic Upcycling of Biomass and Plastic Wastes to Biodegradable Polymer Monomers and Hydrogen Fuel at High Current Densities.

Transformation of biomass and plastic wastes to value-added chemicals and fuels is considered an upcycling process that is beneficial to resource utilization. Electrocatalysis offers a sustainable approach; however, it remains a huge challenge to increase the current density and deliver market-demanded chemicals with high selectivity. Herein, we demonstrate an electrocatalytic strategy for upcycling glycerol (from biodiesel byproduct) to lactic acid and ethylene glycol (from polyethylene terephthalate waste) to glycolic acid, with both products being as valuable monomers for biodegradable polymer production. By using a nickel hydroxide-supported gold electrocatalyst (Au/Ni(OH)2), we achieve high selectivities of lactic acid and glycolic acid (77 and 91%, respectively) with high current densities at moderate potentials (317.7 mA/cm2 at 0.95 V vs RHE and 326.2 mA/cm2 at 1.15 V vs RHE, respectively). We reveal that glycerol and ethylene glycol can be enriched at the Au/Ni(OH)2 interface through their adjacent hydroxyl groups, substantially increasing local concentrations and thus high current densities. As a proof of concept, we employed a membrane-free flow electrolyzer for upcycling triglyceride and PET bottles, attaining 11.2 g of lactic acid coupled with 9.3 L of H2 and 13.7 g of glycolic acid coupled with 9.4 L of H2, respectively, revealing the potential of coproduction of valuable chemicals and H2 fuel from wastes in a sustainable fashion.

AGR2 and FOXA1 as prognostic markers in ER-positive breast cancer.

BACKGROUND: The prognostic role of either forkhead box A1 (FOXA1) or anterior gradient 2 (AGR2) in breast cancer has been found separately. Considering that there were interplays between them depending on ER status, we aimed to assess the statistical interaction between AGR2 and FOXA1 on breast cancer prognosis and examine the prognostic role of the combination of them by ER status. METHODS: AGR2 and FOXA1 expression in tumor tissues were evaluated with tissue microarrays by immunohistochemistry in 915 breast cancer patients with follow up data. The expression levels of these two markers were treated as binary variables, and many different cutoff values were tried for each marker. Survival and Cox proportional hazard analyses were used to evaluate the relationship between AGR2, FOXA1 and prognosis, and the statistical interaction between them on the prognosis was assessed on multiplicative scale. RESULTS: Statistical interaction between AGR2 and FOXA1 on the PFS was significant with all the cutoff points in ER-positive breast cancer patients but not ER-negative ones. Among ER-positive patients, the poor prognostic role of the high level of FOXA1 was significant only in patients with the low level of AGR2, and vice versa. When AGR2 and FOXA1 were considered together, patients with low levels of both markers had significantly longer PFS compared with all other groups. CONCLUSIONS: There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients.

Right Ventricular Function in Takayasu's Arteritis Patients With Pulmonary Artery Involvement Using MRI Feature Tracking.

BACKGROUND: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA-PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important. PURPOSE: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA-PAI patients without PH. STUDY TYPE: Retrospective. POPULATION: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non-PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex- and age-matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography. FIELD STRENGTH/SEQUENCE: 3 T/Cine imaging sequence with a steady-state free precession readout. ASSESSMENT: Cardiac MRI-derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA-PAI patients with and without PH. STATISTICAL TESTS: Student's t test, one-way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P-value of <0.05 was considered statistically significant. RESULTS: Although the TA-PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non-PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non-PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA-PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non-PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non-PH 14.8 ± 3.9%) than those without PH. DATA CONCLUSION: Right ventricular dysfunction was detected in the TA-PAI patients without PH. MR-feature tracking may be an effective method for detecting early cardiac damage in the TA-PAI patients without PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Combined low levels of H4K16ac and H4K20me3 predicts poor prognosis in breast cancer.

BACKGROUND: Results of previous studies about the prognostic roles of histone H4 lysine 16 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3) in breast cancer were inconsistent. Cellular experiments revealed the interplays between H4K16ac and H4K20me3, but no population study explored the interaction between them on the prognosis. METHODS: H4K16ac and H4K20me3 levels in tumors were evaluated by immunohistochemistry for 958 breast cancer patients. Hazard ratios for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction was assessed on multiplicative scale. Concordance index (C-index) was calculated to verify the predictive performance. RESULTS: The prognostic roles of the low level of H4K16ac or H4K20me3 were significant only in patients with the low level of another marker and their interactions were significant. Moreover, compared with joint high levels of both them, only the combined low levels of both them was associated with a poor prognosis but not the low level of single one. The C-index of the clinicopathological model combined the joint expression of H4K16ac and H4K20me3 [0.739 for OS; 0.672 for PFS] was significantly larger than that of the single clinicopathological model [0.699 for OS, P < 0.001; 0.642 for PFS, P = 0.003] or the model combined with the single H4K16ac [0.712 for OS, P < 0.001; 0.646 for PFS, P < 0.001] or H4K20me3 [0.724 for OS, P = 0.031; 0.662 for PFS, P = 0.006]. CONCLUSIONS: There was an interaction between H4K16ac and H4K20me3 on the prognosis of breast cancer and the combination of them was a superior prognostic marker compared to the single one.

University students' fertility awareness and its influencing factors: a systematic review.

INTRODUCTION: In recent years, a growing number of researchers have begun to study fertility awareness (FA). Evidence suggests that college students in their reproductive years have a common understanding of fertility, risk factors for infertility, and assisted reproductive technologies. Therefore, this systematic review summarizes these studies and explores the factors affecting college students' fertility awareness. METHODS: A systematic literature search of databases (PUBMED/MEDLINE, Cochrane, Web of Science, Embase, and EBSCO) was conducted from inception to September 2022. Studies that assessed the levels of fertility awareness and factors influencing college students were considered for the review. The qualities of the included studies were evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. This systematic review is reported according to the preferred reporting items for systematic review (PRISMA) guidelines. RESULTS: Twenty-one articles met the eligibility criteria and were included. The preliminary results showed that participants reported low to moderate FA. Female medical students demonstrated higher levels of fertility awareness. The association between age, years of education, and FA was insufficient. CONCLUSION: The results of the current study suggest that increased FA interventions are warranted, especially for the male, non-medical student population. Governments and educational institutions should strengthen education programs for young students on reproductive health to help them raise awareness about childbirth, and society should provide family support for young people.

A Weekly Diary Study on Playful Study Design, Study Engagement, and Goal Attainment: The Role of Proactive Personality.

Students' learning processes are heavily impeded by the COVID-19 pandemic. Students are experiencing more online learning environment and less face-to-face idea exchange, which may make them feel exhausted and demotivated. Using self-determination and proactivity theories, we propose and examine whether playful study design (PSD)-a proactive study strategy including designing fun and designing competition in learning tasks-is effective in fostering study engagement, which, in turn, improves study goal attainment during the COVID-19 period. Moreover, we examine whether students who are high in proactive personality will benefit more (e.g., reach a higher level of study engagement) when using the PSD strategy. We collected data using a weekly diary approach during four consecutive weeks, including 97 people and 308 within-person observations. Results of multilevel analyses showed that weekly PSD was positively related to weekly study engagement, and in turn, facilitated weekly goal attainment. Moreover, we found that proactive personality moderated and strengthened the positive associations between PSD and goal attainment, study engagement and goal attainment, but not for the relationship between PSD and study engagement. Overall, we provide one of the first attempts to demonstrate how PSD strategy can be used in student study life to improve study engagement and reach their goals. We shed light on how proactive personality can safeguard the success of PSD strategy. Theoretical and practical contributions are discussed.

Clusterization-Triggered Color-Tunable Room-Temperature Phosphorescence from 1,4-Dihydropyridine-Based Polymers.

A series of poly(1,4-dihydropyridine)s (PDHPs) were successfully synthesized via one-pot metal-free multicomponent polymerization of diacetylenic esters, benzaldehyde, and aniline derivatives. These PDHPs without traditional luminescent units were endowed with tunable triplet energy levels by through-space conjugation from the formation of different cluster sizes. The large and compact clusters can effectively extend the phosphorescence wavelength. The triplet excitons can be stabilized by using benzophenone as a rigid matrix to achieve room-temperature phosphorescence. The nonconjugated polymeric clusters can show a phosphorescence emission up to 645 nm. A combination of static and dynamic laser light scattering was conducted for insight into the structural information on formed clusters in the host matrix melt. Moreover, both the fluorescence and phosphorescence emission can be easily tuned by the variation of the excitation wavelength, the concentration, and the molecular weight of the guest polymers. This work provides a unique insight for designing polymeric host-guest systems and a new strategy for the development of long wavelength phosphorescence materials.