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In this study, we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on semen parameters. The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank of the Center for Reproductive Medicine, Shandong University (Jinan, China). The volunteers had normal sperm concentration before infection. Each volunteer provided semen samples before and after infection. We selected 90 days after infection as the cutoff point. Semen parameters within 90 days after infection of 109 volunteers (group A) were compared with semen parameters before infection. Moreover, semen parameters on or after 90 days after infection of 36 volunteers (group B) were compared with semen parameters before infection. Furthermore, based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster, volunteers in group A and B were further divided into two subgroups separately. Semen parameters were compared before and after infection in each subgroup. Our results showed that in this cohort population, the semen quality in volunteers with normal sperm concentrations before infection decreased after SARS-CoV-2 infection within 90 days, while the semen quality returned to preinfection levels after 90 days. The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.

Feeding habits and competitive interactions among dominant grasshopper species in the Xinjiang grasslands (China) were studied under natural conditions through microscopic analyses of insect crop contents. Sex-specific and interindividual differences in feeding habits and interspecific competition were investigated. Analyses of ecological niche width and overlap revealed potential competition among grasshoppers. The results showed significant difference in the sex-specific variations in the feeding habits of the seven grasshoppers; sex-specific variations in feeding range and preferred plants were observed, with females feeding more extensively on host plants, and female and male adults choosing to feed on different plant species. Individuals of all seven grasshoppers showed different degrees of dietary variance, with oligophagous grasshoppers (Oedaleus decorus males, Dericorys annulata, and Bryodema gebleri males) showing a smaller degree of individual dietary variance than polyphagous grasshoppers (Oedipoda caerulescens, Calliptamus coelesyriensis females, Calliptamus barbarus, and Notostaurus albicornis); Calliptamus coelesyriensis and Notostaurus albicornis showed the greatest individual variance in their diets. Oedaleus decorus, Bryodema gebleri, and Calliptamus barbarus consumed primarily Poaceae and exhibited varying foot-plant choice. For example, Oedaleus decorus was observed to have high- preference feeding for Poa annua, Bryodema gebleri for Stipa capillata, and Calliptamus barbarus for Setaria viridis. Dericorys annulata fed primarily on Amaranthaceae, Notostaurus albicornis fed primarily on Poaceae and Amaranthaceae, and Oedipoda caerulescens fed primarily on Asteraceae. Calliptamus barbarus exhibited strong interspecific competition with Oedaleus decorus and Calliptamus coelesyriensis, and Bryodema gebleri demonstrated the strongest interspecific competition with all six other species. Considering the influence of sex on interspecific competition among grasshoppers enhances our understanding of interspecific competitive relationships.

Abstract Background Plastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS. Methods We conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021. Results A total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression. Conclusions Children with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.

Abstract Biofilms serve as crucial cues for settlement and metamorphosis in marine invertebrates. Within bacterial systems, c-di-GMP functions as a pivotal signaling molecule regulating both biofilm formation and dispersion. However, the molecular mechanism of how c-di-GMP modulates biofilm-induced larval metamorphosis remains elusive. Our study reveals that the deletion of a c-di-GMP related gene in Pseudoalteromonas marina led to an increase in the level of bacterial c-di-GMP by knockout technique, and the mutant strain had an enhanced ability to produce more outer membrane vesicles (OMVs) and lipopolysaccharides (LPS). The mutant biofilms had higher induction activity for larval metamorphosis in mussels Mytilus coruscus, and OMVs play a major role in the induction activity. We further explored the function of LPS in OMVs. Extracted LPS induced high larval metamorphosis rate, and LPS content were subject to c-di-GMP and LPS-biosynthesis gene. Thus, we postulate that the impact of c-di-GMP on biofilm-induced metamorphosis is mediated through OMVs and LPS.

Abstract RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Abstract Background The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. Methods A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein–Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. Results A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value 1.5 or HR/N

Abstract Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

Optimal intestinal health and functionality are essential for animal health and performance, and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control mechanisms. Given the potential of essential oil (EO) in improving animal performance and improving feed palatability, we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and microbiota. Cinnamaldehyde (100 mg/kg), carvacrol (100 mg/kg), and their mixtures (including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol) were supplemented into the diets of 240 nursery pigs for 42 d, and data related to performance were measured. Thereafter, the influence of EO on intestinal health, appetite and gut microbiota and their correlations were explored. EO supplementation increased (P

ABSTRACT Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3′,5′-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase DNA integrity scanning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of disA was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in Actinobacteria and thus the global control of cellular physiology.IMPORTANCESince the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium Saccharopolyspora erythraea as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased disA expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis.

Introduction: Baló's concentric sclerosis (BCS) is a rare type of central nervous system demyelinating disorder. Most patients with BCS are treated with corticosteroids, and spontaneous remission has seldom been described. Case presentation: A 46-year-old man presented with a subacute-onset headache and memory loss. Brain magnetic resonance imaging (MRI) revealed multiple onion-shaped ring lesions with mild enhancement in the outermost ring. A brain biopsy revealed significant myelin loss. The diagnosis of BCS was established based on the MRI results and pathological findings. Interestingly, the patient recovered almost completely without immunotherapy, with repeated brain MRI at the 1-year follow-up showing an obvious reduction in the extent of the lesions. Conclusion: Neurologists should improve the recognition of the typical MRI features of BCS to avoid unnecessary biopsies. Although rare, spontaneous remission can be observed in clinical practice.

ABSTRACT: Atrazine (ATR) is widely used worldwide as a commercial herbicide, Diaminochlorotriazine (DACT) is the main metabolite of ATR in the organism. Both of them disrupt the production of steroids and induce abnormal reproductive development. The granulosa cells (GCs) are important for growth and reproduction of animals. However, the toxicity of ATR on the GCs of birds is not well clarified. To evaluate the effect of the environmental pollutant ATR on bird GCs. The quail GCs were allotted into 7 groups, C (The medium of M199), A20 (20 µM ATR), A100 (100 µM ATR), A250 (250 µM ATR), D20 (20 µM DACT), D100 (100 µM DACT) and D200 (200 µM DACT). The results demonstrated that ATR reduced the viability of GCs, disrupted mitochondrial structure (including mitochondrial cristae fragmentation and the mitochondrial morphology disappearance) and decreased mitochondrial membrane potential. Meanwhile, ATR interfered with the expression of key factors in the steroid synthesis pathway, inducing the secretion of the sex hormones E2 and P in GCs. which in turn induced apoptosis. Furthermore, the Nrf2/ARE pathway as a potential target to ameliorate ATR-induced endocrine disruption in GCs for proper reproductive functions. Our research provides a new perspective for understanding the effects of ATR on reproductive functions in birds.

We extend the entanglement bootstrap program to (3+1)-dimensions. We study knotted excitations of (3+1)-dimensional liquid topological orders and exotic fusion processes of loops. As in previous work in (2+1)-dimensions [Ann. Phys. 418, 168164(2020), Phys. Rev. B 103, 115150 (2021)], we define a variety of superselection sectors and fusion spaces from two axioms on the ground state entanglement entropy. In particular, we identify fusion spaces associated with knots. We generalize the information convex set to a new class of regions called immersed regions, promoting various theorems to this new context. Examples from solvable models are provided; for instance, a concrete calculation of knot multiplicity shows that the knot complement of a trefoil knot can store quantum information. We define spiral maps that allow us to understand consistency relations for torus knots as well as spiral fusions of fluxes.

Objective To explore the risk factors for neutropenia (grade 2 or higher) during postoperative adjuvant radiotherapy for breast cancer. Methods A total of 93 patients with breast cancer treated by postoperative adjuvant radiotherapy in Shaanxi Provincial People’s Hospital from January 2018 to December 2020 were assigned to a control group (no neutropenia or grade 1 neutropenia, n=62) and an observation group (grade 2 or higher neutropenia, n=31). The clinical data of the two groups were analyzed by univariate and logistic regression analyses to determine the independent risk factors for grade 2 or higher neutropenia, and the predictive efficacy of risk factors was established by the receiver operating characteristic (ROC) curve. Results The univariate analysis results showed that there were significant differences between the two groups in molecular types of breast cancer, white blood cell count and absolute neutrophil count at the first visit, proportion of patients with grade 4 myelosuppression during chemotherapy, white blood cell count, absolute neutrophil count, hemoglobin before radiotherapy, planning target volume (PTV), mean radiotherapy dose to the sternum (Dmean), and ratio of volume exposed to radiation greater than 20 Gy to total vo-lume and ratio of volume exposed to radiation greater than 30 Gy to total volume in the sternum (χ2=4.511,9.900,t=2.286-9.900,P733.28 mL and sternum Dmean >2 213.5 cGy are independent risk factors for grade 2 or higher neutropenia during postoperative adjuvant radiotherapy for breast cancer, and the combination of the two indices can improve the predictive efficacy for the occurrence of neutropenia.