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AIM: To compare the safety and clinical outcomes of subconjunctival trypsin and dexamethasone (DEX) injections in the treatment of anterior chamber fibrin exudates in eyes with globe rupture following primary wound repair and vitrectomy. METHODS: A retrospective analysis included 42 males and 10 females (mean age 46.0±6.0y, range 34 to 58y) who underwent primary wound sutures and vitrectomy for globe rupture. Patients with pupil-covered fibrinous exudate or/and membrane in the anterior chamber were treated. On the first postoperative day, subconjunctival injections of either 5000 units (0.4 mL) of trypsin solution (n=25) or 0.5 mL (1 mg) DEX (n=27) were administered to accelerate exudate absorption. Efficacy was assessed by observing break time and partial absorption of the fibrin exudate membrane. Safety and comfort were evaluated by monitoring intraocular pressure (IOP), allergy, pain, and foreign body sensation. RESULTS: Both groups achieved 1/3 absorption of the anterior chamber fibrin exudate membrane, but the trypsin group exhibited shorter break time and partial absorption time compared to the DEX group (P

Abstract Background Parturition is an inflammation process. Exaggerated inflammatory reactions in infection lead to preterm birth. Although nuclear factor kappa B (NF-κB) has been recognized as a classical transcription factor mediating inflammatory reactions, those mediated by NF-κB per se are relatively short-lived. Therefore, there may be other transcription factors involved to sustain NF-κB-initiated inflammatory reactions in gestational tissues in infection-induced preterm birth. Methods Cebpd-deficient mice were generated to investigate the role of CCAAT enhancer-binding protein δ (C/EBPδ) in lipopolysaccharide (LPS)-induced preterm birth, and the contribution of fetal and maternal C/EBPδ was further dissected by transferring Cebpd −/− or WT embryos to Cebpd −/− or WT dams. The effects of C/EBPδ pertinent to parturition were investigated in mouse and human myometrial and amnion cells. The interplay between C/EBPδ and NF-κB was examined in cultured human amnion fibroblasts. Results The mouse study showed that LPS-induced preterm birth was delayed by Cebpd deficiency in either the fetus or the dam, with further delay being observed in conceptions where both the dam and the fetus were deficient in Cebpd. Mouse and human studies showed that the abundance of C/EBPδ was significantly increased in the myometrium and fetal membranes in infection-induced preterm birth. Furthermore, C/EBPδ participated in LPS-induced upregulation of pro-inflammatory cytokines as well as genes pertinent to myometrial contractility and fetal membrane activation in the myometrium and amnion respectively. A mechanistic study in human amnion fibroblasts showed that C/EBPδ, upon induction by NF-κB, could serve as a supplementary transcription factor to NF-κB to sustain the expression of genes pertinent to parturition. Conclusions C/EBPδ is a transcription factor to sustain the expression of gene initiated by NF-κB in the myometrium and fetal membranes in infection-induced preterm birth. Targeting C/EBPδ may be of therapeutic value in the treatment of infection-induced preterm birth.

Abstract Background Nurses’ competence in clinical research is a key element in promoting high quality in the discipline of nursing, and the ethical aspects of research are of paramount importance. Therefore, nurses need to have a comprehensive understanding of the ethics associated with clinical research, which is an integral part of safeguarding the safety of subjects, ensuring the quality of nursing clinical research, and improving the ethical standardization of clinical research. Methods A cross-sectional survey was conducted on 304 nurses in a province of China between April 2023 and September 2023, utilizing convenience sampling. The survey questionnaire comprised two sections: a general information form and a questionnaire focusing on nurses’ knowledge and attitudes towards clinical research ethics. Data analysis encompassed descriptive statistics, t-tests, one-way ANOVA, and multiple linear regression. Results A total of 320 questionnaires were distributed, of which 304 were valid. The ethical attitude of nurses in clinical research was better (91.17 ± 15.96), while the cognitive score was lower (63.08 ± 12.30). The results of multiple linear regression analysis showed that degree, grade of hospital (I, II or III), technical title, number of clinical projects chaired in one year and whether the respondent has ever participated in an ethics training were the five factors influencing the knowledge of clinical research ethics (F = 9.341, P

When simulating drying-rewetting process of grid cells in numerical groundwater modeling using the block-centered finite-difference approach, the models is highly probable to run into non-convergence, which could greatly affect the applicability of groundwater models. This study used ideal case and practical simulation in Denmark to comprehensively compare the simulation capabilities and characteristics of two algorithms, namely the empirical trial (ET) method proposed by MODFLOW and the always active cell (AAC) method proposed by COMUS, in the drying-rewetting simulation. The results show that: (1) For the ET method, the selection of parameter combination has a significant influence on the model convergence and the simulation results. It is compulsory to continuously optimize the parameter to avoid model failures such as non-convergence and large simulation errors when using the ET method, which greatly increases the difficulty of groundwater model application and time cost. (2) The simulation results from the AAC method are more reliable than those from the ET method. Theoretically, the effect of the AAC method is equivalent to the optimal parameter set in the ET method. Therefore, parameter optimization is no longer needed in the AAC method, which can effectively reduce the difficulty of using groundwater models and meanwhile reduce the uncertainty of simulation results. (3) The numerical accuracy of the intercell horizontal hydraulic conductance in the AAC method is consistent with that of the classical harmonic average method, demonstrating that the AAC method can also be used in the simulation without the drying-rewetting process. In summary, the AAC method is more suitable for simulating the drying-rewetting process of groundwater model cells and is expected to be more widely used in groundwater numerical simulation.

Abstract Thyroid cancer (TC) is a significant global healthcare burden. However, the lack of comprehensive data has impeded our understanding of its global impact. We aimed to examine the burden of TC and its trends at the global, regional, and national levels using data stratified by sociodemographic index (SDI), sex, and age. Data on TC, including incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, were obtained from the Global Burden of Disease Study 2021. Estimated annual percentage changes (EAPCs) were calculated to assess the incidence rate, mortality, and DALYs trends. The incidence, mortality, and DALYs of TC in 2021 were 249,538 (95% uncertainty interval: 223,290–274,638), 44,799 (39,925–48,541), and 646,741 (599,119–717,357), respectively. The age-standardized incidence rate (ASIR) in 2021 was 2.914 (2.607–3.213), with an EAPC of 1.25 (1.14–1.37) compared to 1990. In 2021, the age-standardized death rate (ASDR) was 0.53 (0.47–0.575) and age-standardized DALYs rate was 14.571 (12.783–16.115). Compared with 1990, the EAPCs of ASDR and age-standardized DALYs rate showed decreasing trends, at − 0.24 (− 0.27 to − 0.21) and − 0.14 (− 0.17 to − 0.11), respectively. Low SDI regions showed the highest ASDR and age-standardized DALYs rate, at 0.642 (0.516–0.799) and 17.976 (14.18–23.06), respectively. Low-middle SDI regions had the highest EAPCs for ASDR and age-standardized DALYs rate, at 0.74 (0.71–0.78) and 0.67 (0.63–0.7), respectively. Females exhibited decreasing trend in ASDR and age-standardized DALYs rate, with EAPCs of − 0.58 (− 0.61 to − 0.55) and − 0.45 (− 0.47 to − 0.42), respectively. In contrast, males showed an increasing trend in ASDR and age-standardized DALYs rate, with EAPCs of 0.41 (0.35–0.46) for both. In high-income regions, most countries with decreased annual changes in deaths experience increasing age-related deaths. Over the past few decades, a notable increase in TC incidence and decreased mortality has been observed globally. Regions characterized by lower SDI, male sex, and an aging population exhibited no improvement in TC mortality. Effective resource allocation, meticulous control of risk factors, and tailored interventions are crucial for addressing these issues.

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the “bibliometrix” R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co‐cited journal. These publications come from 14,801 authors, with Liu Zong‐Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong‐Yan having published the most papers. Ronald S. Weinstein was co‐cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. Methods We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. Results A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. Conclusions These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Abstract Searching for topological superconductors that host topological charge-neutral Majorana zero-modes at edges has become a central problem in condensed matter research due to their potential applications for quantum computations. Meanwhile, electron correlations in solid-state materials enhance quantum fluctuations and give rise to various quantum many-body phases. Whether these electron correlations alone would lead to topological superconductivity is a fundamentally important open problem. Here, we theoretically find the correlation-driven topological superconductivity in a class of Kondo lattice materials. Therein, the odd-parity Kondo hybridization mediates ferromagnetic spin-spin coupling and leads to spin-triplet pairing between local moments. Triplet $$p\pm i{p}^{{\prime} }$$ p ± i p ′ -wave topological superconductivity with Majorana zero modes at edges is reached when Kondo hybridization co-exists with the triplet pairings. Our results offer a detailed understanding of the experimental observations on UTe2, a ferromagnetic heavy-electron triplet superconductor. Our approach to topological superconductivity shows advantages over the heterostructure approach by proximity effect.

Abstract Background A retrotransposon HORT1 in the promoter of the anthocyanin activator gene PeMYB11, microRNA858 (miR858) that targets PeMYB11, and a repressor PeMYBx have been implicated in pigmentation patterning diversity of harlequin Phalaenopsis orchids. However, the interrelationship among them remains to be elucidated. Results To understand how these factors interact to generate anthocyanin spots in Phalaenopsis, we successfully developed a mathematical model based on the known reaction–diffusion system to simulate their interplay and refined the conceptual biological model. Intriguingly, the expression of both PeMYBx and PeMYB11 were in phase for purple spot formation, even though they showed adverse effects on anthocyanin accumulations. An increase in the self-activation rate of PeMYB11 resulted in the increased size of purple spots, but no effects on spot fusion. Decreased degradation rate of miR858 in the purple regions, led to disruption of the formation of spotted pigmentation patterning and a full-red pigmentation pattern. Significantly, the reduced miR858 level promotes the fusion of large dark purple dots induced by the solo-LTR of HORT1, eventually generating the purple patches. In addition, the spatially heterogeneous insertion of HORT1 caused by the remnant solo-LTR of HORT1 derived from random homologous unequal recombination of HORT1 in individual cells of floral organs could explain the diverse pigmentation patterning of harlequin Phalaenopsis. Conclusions This devised model explains how HORT1 and miR858 regulate the formation of the pigmentation patterning and holds great promise for developing efficient and innovative approaches to breeding harlequin Phalaenopsis orchids.

Abstract To explore the related factors of turnover intention in clinical research coordinators (CRCs) and assess the mediating effects of professional identity on the association between job burnout and turnover intention. In China, CRC has become increasingly common among clinical trial teams in recent years. However, limited published research focused on the status of turnover intention in CRCs. We invited all the 220 CRCs currently working at Hunan Cancer Hospital located in Changsha city in the central south of China from March to June 2018. Participants were asked to complete structured questionnaires regarding basic demographic information, job burnout, professional identity and turnover intention. A total of 202 participants were included in this study, with a response rate of 91.82%. The main reason for turnover intention among CRCs was human resources, followed by communications, management and material resources (per item score in each dimension: 2.14 vs. 2.43 vs. 2.65 vs. 2.83). All the correlations among job burnout, professional identity and turnover intention were statistically significant, with coefficients ranging from −0.197 to 0.615. Multiple liner regression analysis showed that older age, longer workhours per week, and lower level of professional identity were associated with the prevalence of turnover intention among CRCs. Besides, the association between job burnout and turnover intention was fully mediated by professional identity. This study revealed the status and causes of turnover intention among Chinese CRCs. Effective measures on decreasing working time and improving professional identity should be taken in order to reduce CRCs’ turnover intention.

Abstract The purpose of this study was to investigate the relationship between Inflammatory Prognostic Index (IPI) levels and Contrast-Induced Nephropathy (CIN) risk and postoperative clinical outcomes in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). A total of 3,340 consecutive patients who underwent CAG and/or PCI between May 2017 and December 2022 were enrolled in this study. Based on their baseline IPI levels, patients were categorized into four groups. Clinical characteristics and postoperative outcomes were compared among these groups. In-hospital outcomes focused on CIN risk, repeated revascularization, major bleeding, and major adverse cardiovascular events (MACEs), while the long-term outcome examined the all-cause readmission rate. Quartile analysis found a significant link between IPI levels and CIN risk, notably in the highest quartile (P

Abstract Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

IntroductionFetal membrane inflammation is an integral event of parturition. However, excessive pro-inflammatory cytokines can impose threats to the fetus. Coincidentally, the fetal membranes express abundant 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which generates biologically active cortisol to promote labor through induction of prostaglandin synthesis. Given the well-recognized anti-inflammatory actions of glucocorticoids, we hypothesized that cortisol regenerated in the fetal membranes might be engaged in restraining fetus-hazardous pro-inflammatory cytokine production for the safety of the fetus, while reserving pro-labor effect on prostaglandin synthesis to ensure safe delivery of the fetus.MethodsThe hypothesis was examined in human amnion tissue and cultured primary human amnion fibroblasts as well as a mouse model.Results11β-HSD1 was significantly increased in the human amnion in infection-induced preterm birth. Studies in human amnion fibroblasts showed that lipopolysaccharide (LPS) induced 11β-HSD1 expression synergistically with cortisol. Cortisol completely blocked NF-κB-mediated pro-inflammatory cytokine expression by LPS, but STAT3-mediated cyclooxygenase 2 expression, a crucial prostaglandin synthetic enzyme, remained. Further studies in pregnant mice showed that corticosterone did not delay LPS-induced preterm birth, but alleviated LPS-induced fetal organ damages, along with increased 11β-HSD1, cyclooxygenase 2, and decreased pro-inflammatory cytokine in the fetal membranes.DiscussionThere is a feed-forward cortisol regeneration in the fetal membranes in infection, and cortisol regenerated restrains pro-inflammatory cytokine expression, while reserves pro-labor effect on prostaglandin synthesis. This dual role of cortisol regeneration can prevent excessive pro-inflammatory cytokine production, while ensure in-time delivery for the safety of the fetus.

Abstract Background Staphylococcus aureus secretes a variety of proteins including virulence factors that cause diseases. PrsA, encoded by many Gram-positive bacteria, is a membrane-anchored lipoprotein that functions as a foldase to assist in post-translocational folding and helps maintain the stability of secreted proteins. Our earlier proteomic studies found that PrsA is required for the secretion of protein A, an immunoglobulin-binding protein that contributes to host immune evasion. This study aims to investigate how PrsA influences protein A secretion. Results We found that in comparison with the parental strain HG001, the prsA-deletion mutant HG001ΔprsA secreted less protein A. Deleting prsA also decreased the stability of exported protein A. Pulldown assays indicated that PrsA interacts with protein A in vivo. The domains in PrsA that interact with protein A are mapped to both the N- and C-terminal regions (NC domains). Additionally, the NC domains are essential for promoting PrsA dimerization. Furthermore, an immunoglobulin-binding assay revealed that, compared to the parental strain HG001, fewer immunoglobulins bound to the surface of the mutant strain HG001ΔprsA. Conclusions This study demonstrates that PrsA is critical for the folding and secretion of protein A. The information derived from this study provides a better understanding of virulent protein export pathways that are crucial to the pathogenicity of S. aureus.

Background/purpose: The chemo-mechanical caries-removal technique is known to offer advantages of selective dentin caries treatment while leaving healthy dental tissues intact. However, current sodium hypochlorite based reagents usually excessively damage dentin collagen. Therefore, the purpose of this study was to develop a novel chemo-mechanical caries-removal system to preserve the collagen network for subsequent prosthetic restorations. Materials and methods: The calfskin-derived collagen was chosen as a model system to investigate the dissolution behavior of collagen under different operating conditions of chemical-ultrasonic treatment systems. The molecular weight, triple-helix structure, the morphology, and functional group of collagen after treatment were investigated. Results: Various concentrations of sodium hypochlorite or zinc chloride together with ultrasonic machinery were chosen to investigate. The outcomes of circular dichroism (CD) spectra demonstrated stability of the triple-helix structure after treatment of a zinc chloride solution. In addition, two apparent bands at molecular weights (MWs) of 130 and 121 kDa evidenced the stability of collagen network. The positive 222 nm and 195 nm negative CD absorption band indicated the existence of a triple-helix structure for type I collagen. The preservation of the morphology and functional group of the collagen network on the etched dentin surface were investigated by in vitro dentin decalcification model. Conclusion: Unlike NaOCl, the 5 wt% zinc chloride solution combined with ultra-sonication showed dissolution rather than denature as well as degradation of the dentin collagen network. Additional in vivo evaluations are needed to verify its usefulness in clinical applications.