12-O-deacetyl-phomoxanthone A inhibits ovarian tumor growth and metastasis by downregulating PDK4.

AIMS: The xanthone dimer 12-O-deacetyl-phomoxanthone A (12-ODPXA) was extracted from the secondary metabolites of the endophytic fungus Diaporthe goulteri. The 12-ODPXA compound exhibited anticancer properties in murine lymphoma; however, the anti-ovarian cancer (OC) mechanism has not yet been explored. Therefore, the present study evaluated whether 12-ODPXA reduces OC cell proliferation, metastasis, and invasion by downregulating pyruvate dehydrogenase kinase (PDK)4 expression. METHODS: Cell counting kit-8, colony formation, flow cytometry, wound healing, and transwell assays were performed to examine the effects of 12-ODPXA on OC cell proliferation, apoptosis, migration, and invasion. Transcriptome analysis was used to predict the changes in gene expression. Protein expression was determined using western blotting. Glucose, lactate, and adenosine triphosphate (ATP) test kits were used to measure glucose consumption and lactate and ATP production, respectively. Zebrafish xenograft models were constructed to elucidate the anti-OC effects of 12-ODPXA. RESULTS: The 12-ODPXA compound inhibited OC cell proliferation, migration, invasion, and glycolysis while inducing cell apoptosis via downregulation of PDK4. In vivo experiments showed that 12-ODPXA suppressed tumor growth and migration in zebrafish. CONCLUSION: Our data demonstrate that 12-ODPXA inhibits ovarian tumor growth and metastasis by downregulating PDK4, revealing the underlying mechanisms of action of 12-ODPXA in OC.

Coatless modification of 3D-printed Ti6Al4V implants through tailored Cu ion implantation combined with UV photofunctionalization to enhance cell attachment, osteogenesis and angiogenesis.

The three-dimensional-printed Ti6Al4V implant (3DTi) has been widely accepted for the reconstruction of massive bone defects in orthopedics owing to several advantages, such as its tailored shape design, avoiding bone graft and superior bone-implant interlock. However, the osteoinduction activity of 3DTi is inadequate when applied clinically even though it exhibits osteoconduction. This study developes a comprehensive coatless strategy for the surface improvement of 3DTi through copper (Cu) ion implantation and ultraviolet (UV) photofunctionalization to enhance osteoinductivity. The newly constructed functional 3DTi (UV/Ti-Cu) achieved stable and controllable Cu doping, sustained Cu2+ releasing, and increased surface hydrophilicity. By performing cellular experiments, we determined that the safe dose range of Cu ion implantation was less than 5×1016 ions/cm2. The implanted Cu2+ enhanced the ALP activity and the apatite formation ability of bone marrow stromal cells (BMSCs) while slightly decreasing proliferation ability. When combined with UV photofunctionalization, cell adhesion and proliferation were significantly promoted and bone mineralization was further increased. Meanwhile, UV/Ti-Cu was conducive to the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, theoretically facilitating vascular coupling osteogenesis. In conclusion, UV/Ti-Cu is a novel attempt to apply two coatless techniques for the surface modification of 3DTi. In addition, it is considered a potential bone substrate for repairing bone defects.

Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study.

Respiratory viral infections (RVIs) are common reasons for healthcare consultations. The inpatient management of RVIs consumes significant resources. From 2009 to 2014, we assessed the costs of RVI management in 4776 hospitalized children aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by detailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU ('non-ICU') versus management requiring ICU care ('ICU') added up to EUR 2767.14 (non-ICU) vs. EUR 29,941.71 (ICU) for influenza, EUR 2713.14 (non-ICU) vs. EUR 16,951.06 (ICU) for RSV infections, and EUR 2767.33 (non-ICU) vs. EUR 14,394.02 (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all eight RVIs studied: influenza, RSV, hRV, adenovirus (hAdV), metapneumovirus (hMPV), parainfluenza virus (hPIV), bocavirus (hBoV), and seasonal coronavirus (hCoV) infections. ICU costs for influenza, however, exceeded all other RVIs. At the time of the study, influenza was the only RVI with antiviral treatment options available for children, but only 9.8% of influenza patients (non-ICU) and 1.5% of ICU patients with influenza received antivirals; only 2.9% were vaccinated. Future studies should investigate the economic impact of treatment and prevention of influenza, COVID-19, and RSV post vaccine introduction.

The anti-atherosclerotic effect of Paeonol against the lipid accumulation in macrophage-derived foam cells by inhibiting ferroptosis via the SIRT1/NRF2/GPX4 signaling pathway.

Atherosclerosis (AS) is the underlying cause of many severe vascular diseases and is primarily characterized by abnormal lipid metabolism. Paeonol (Pae), a bioactive compound derived from Paeonia Suffruticosa Andr., is recognized for its significant role in reducing lipid accumulation. Our research objective is to explore the link between lipid buildup in foam cells originating from macrophages and the process of ferroptosis, and explore the effect and mechanism of Pae on inhibiting AS by regulating ferroptosis. In our animal model, ApoE-deficient mice, which were provided with a high-fat regimen to provoke atherosclerosis, were administered Pae. The treatment was benchmarked against simvastatin and ferrostatin-1. The results showed that Pae significantly reduced aortic ferroptosis and lipid accumulation in the mice. In vitro experiments further demonstrated that Pae could decrease lipid accumulation in foam cells induced by oxidized low-density lipoprotein (LDL) and challenged with the ferroptosis inducer erastin. Crucially, the protective effect of Pae against lipid accumulation was dependent on the SIRT1/NRF2/GPX4 pathway, as SIRT1 knockdown abolished this effect. Our findings suggest that Pae may offer a novel therapeutic approach for AS by inhibiting lipid accumulation through the suppression of ferroptosis, mediated by the SIRT1/NRF2/GPX4 pathway. Such knowledge has the potential to inform the creation of novel therapeutic strategies aimed at regulating ferroptosis within the context of atherosclerosis.

Aging-induced tRNAGlu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.

Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.

Investigating fear of cancer recurrence among female breast cancer survivors and their spouses in southwest China: a cross-sectional study.

OBJECTIVES: Examining fear of cancer recurrence (FCR) among breast cancer survivors and their spouses, and the protective effect of family resilience on FCR among couples affected by breast cancer. DESIGN: Cross-sectional survey design. SETTING: Ten general grade IIIa (>500 beds) hospitals in southwest China. PARTICIPANTS: Overall, 392 early breast cancer survivors and their spousal caregivers (N=392) were recruited from cancer centres in hospitals. PRIMARY AND SECONDARY OUTCOME MEASURES: Spouses' and survivors' FCR were the primary outcome measures. Family resilience and perceived stress were the secondary outcome measures. Using a convenience sampling method, we collected data on-site using paper questionnaires. The Chinese version of the Family Resilience Assessment Scale, Perceived Stress Scale, Fear of Progression Questionnaire Short Form and Fear of Progression Questionnaire-Short Form for spouses were used to evaluate the outcomes. RESULTS: The model accounted for 66.3% and 53.6% of the variance in spouses' FCR and survivors' FCR, respectively. Family resilience directly negatively affected perceived stress and spouses' and survivors' FCR (ß=-0.22; ß=-0.13; ß=-0.19). Perceived stress was a partial mediator of the association between family resilience and survivors' FCR (ß=-0.070; 95% CI :-0.151 to -0.022). Spouses' FCR partially mediated the association between family resilience and survivors' FCR (ß=-0.048; 95% CI= -0.092 to -0.015). Perceived stress and spouses' FCR played a significant chain-mediated role between family resilience and survivors' FCR (ß=-0.061; 95% CI: -0.119 to -0.022). CONCLUSIONS: Family-centred approaches to reducing survivors' perceived stress can improve the psychological well-being of couples affected by breast cancer and ultimately reduce FCR. Medical staff should consider the psychological feelings of survivors and their spousal caregivers when devising the intervention plan, which should address the families' potential and mobilise family and community resources for increasing family resilience.

Accelerated marine carbon cycling forced by tectonic degassing over the Miocene Climate Optimum.

Global warming during the Miocene Climate Optimum (MCO, ∼17-14 million years ago) is associated with massive carbon emissions sourced from the flood basalt volcanism and ocean crustal production. However, the perturbation of tectonic carbon degassing on the interaction between climate change and carbon cycle remains unclear. Here, through time-evolutive phase analysis of new and published high-resolution benthic foraminiferal oxygen (δ18O) and carbon (δ13C) isotope records from the global ocean, we find that variations in the marine carbon cycle lead the climate-cryosphere system (δ13C-lead-δ18O) on 405,000-year eccentricity timescales during the MCO. This is in contrast to the previously reported climate-lead-carbon (δ18O-lead-δ13C) scenario during most of the Oligo-Miocene (∼34-6 million years ago). Further sensitivity analysis and model simulations suggest that the elevated atmospheric CO2 concentrations and the resulting greenhouse effect strengthened the low-latitude hydrological cycle during the MCO, accelerating the response of marine carbon cycle to eccentricity forcing. Tropical climate processes played a more important role in regulating carbon-cycle variations when Earth's climate was in a warm regime, as opposed to the dominant influence of polar ice-sheet dynamics during the Plio-Pleistocene (after ∼6 million years ago).

Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma.

Cytokine release syndrome (CRS) is the most common complication of chimeric antigen receptor redirected T cells (CAR-T) therapy. CAR-T toxicity management has been greatly improved, but CRS remains a prime safety concern. Here we follow serum cytokine levels and circulating immune cell transcriptomes longitudinally in 26 relapsed/refractory multiple myeloma patients receiving the CAR-T product, ciltacabtagene autoleucel, to understand the immunological kinetics of CRS. We find that although T lymphocytes and monocytes/macrophages are the major overall cytokine source in manifest CRS, neutrophil activation peaks earlier, before the onset of severe symptoms. Intracellularly, signaling activation dominated by JAK/STAT pathway occurred prior to cytokine cascade and displayed regular kinetic changes. CRS severity is accurately described and potentially predicted by temporal cytokine secretion signatures. Notably, CAR-T re-expansion is found in three patients, including a fatal case characterized by somatic TET2-mutation, clonal expanded cytotoxic CAR-T, broadened cytokine profiles and irreversible hepatic toxicity. Together, our findings show that a latent phase with distinct immunological changes precedes manifest CRS, providing an optimal window and potential targets for CRS therapeutic intervention and that CAR-T re-expansion warrants close clinical attention and laboratory investigation to mitigate the lethal risk.

Paeonol Attenuates Atherosclerosis by Inhibiting Vascular Smooth Muscle Cells Senescence via SIRT1/P53/TRF2 Signaling Pathway.

Atherosclerosis is a chronic inflammatory disease leading to various vascular diseases. Vascular smooth muscle cell (VSMC) senescence promotes atherosclerotic inflammation and the formation of plaque necrosis core, in part through telomere damage mediated by a high-fat diet. Our previous research found that paeonol, a potential anti-inflammatory agent extracted from Cortex Moutan, could significantly improve VSMCs dysfunction. However, the impact of paeonol on the senescence of VSMCs remains unexplored. This study presents the protective effects of paeonol on VSMCs senescence, and its potential activity in inhibiting the progression of atherosclerosis in vivo and in vitro. Sirtuin 1 (SIRT1) is a nuclear deacetylase involved in cell proliferation, senescence, telomere damage, and inflammation. Here, SIRT1 was identified as a potential target of paeonol having anti-senescence and anti-atherosclerosis activity. Mechanistic studies revealed that paeonol binds directly to SIRT1 and then activates the SIRT1/P53/TRF2 pathway to inhibit VSMCs senescence. Our results suggested that SIRT1-mediated VSMCs senescence is a promising druggable target for atherosclerosis, and that pharmacological modulation of the SIRT1/P53/TRF2 signaling pathway by paeonol is of potential benefit for patients with atherosclerosis.

The influence of direct anterior approach and postero-lateral approach on wound complications after total hip arthroplasty: A meta-analysis.

To date, we have reviewed the synthesis literature critically through four databases: PubMed, Embase, Cochrane Library and Web of Science. Eight relevant studies were examined after compliance with the criteria for inclusion and exclusion, as well as documentation quality evaluation. This report covered all randomised, controlled studies of total hip arthroplasty (THA) comparing the direct anterior approach (DAA) with the postero-lateral approach (PLA). The main result was surgical site infection rate. The secondary results were duration of the operation, length of the incision and VAS score after surgery. The results of the meta-analyses of wound infections in the present trial did not show any statistically significant difference in DAA versus PLA (between DAA and PLA) (OR = 1.42, 95%CI: 0.5 to 4.04, p = 0.51). Compared with PLA, DAA had shorter surgical incision (WMD = -3.2, 95%CI: -4.00 to -2.41; p < 0.001) and longer operative times(WMD = 14. 67, 95%CI: 9.24 to 20.09; p < 0.001). Postoperative VAS scores were markedly lower in DAA compared with PLA within 6 weeks of surgery (p < 0.05), with low heterogeneities(I2 = 0). We found that DAA did not differ significantly from PLA in terms of the risk of wound infection for THA and that the surgical incisions was shorter and less postoperative pain after surgery, even though DAA surgery takes longer.

High-performance aqueous rechargeable NiCo//Zn battery with molybdate anion intercalated CoNi-LDH@CP bilayered cathode.

Seeking cathode materials with high areal capacity and excellent cycling tolerance is a key step to develop aqueous rechargeable zinc-based alkaline batteries with high energy density, power density and excellent stability. Here, the bilayered cathode composite (MCN-LDH@CP) of molybdate intercalated cobalt-nickel layered hydroxide nanosheets (MCN-LDH) grown on cobalt phosphate octahydrate microsheet (CP) was prepared by a two-step hydrothermal process. Molybdate intercalation significantly reduces the thickness of cobalt-nickel layered hydroxide, greatly increases its specific surface area, regulates its pore distribution, increases the crystal plane spacing, promotes the diffusion rate of hydroxide in it, and increases its specific capacity. Meanwhile, the bilayered MCN-LDH@CP electrode significantly improved the areal energy density (2.89 mWh/cm2) and peak power density (111.22 mW/cm2) and cycle stability (97.8 % after 7000 cycles) of the CoNi//Zn battery. The excellent stability is mainly due to the fact that the MCN-LDH overlay inhibits the loss of P element of CP and improves the structural stability of the sample. The quasi-solid-state MCN-LDH@CP//Zn battery can still charge a mobile phone even when hammered and pierced, showing excellent safety and reliability. This work opens a new avenue to develop CoNi//Zn batteries with high energy density, power density and excellent tolerance.

In situ generated iron oxide nanosheet on iron foam electrode for enhanced electro-Fenton performance toward pharmaceutical wastewater treatment.

Electro-Fenton (EF) is considered to be an effective technology for the purification of organic wastewater containing antibiotics, but the construction of accessible and efficient heterogeneous EF catalytic materials still faces challenges. In this study, an iron foam-derived electrode (FeOx/if-400) was prepared by a simple method (chemical oxidation combined heat treatment). The fabricated electrode presented great EF degradation efficiency under wide pH range (almost completely removing 50 mg L-1 TNZ within 60 min) and maintained great stability after consecutive operation (>95% removal after six cycles). Also, the FeOx/if-400 electrode showed good purification ability for pharmaceutical wastewater as evaluated by the quadrupole time-of-flight mass spectrometry and the three-dimensional excitation-emission matrix fluorescence spectroscopy. Based on experimental results, characterization analysis, and density functional theory (DFT) calculations, the EF reaction mechanism of FeOx/if-400 electrode and the organics degradation pathways in simulated and real matrices were proposed. Significantly, the biotoxicity assessment of the degradation intermediate products was revealed by ECOSAR software and relative inhibition of E. coli, which fully proved the environmental friendliness of the EF process by the FeOx/if-400 cathode. This work provides a green and effective EF system, showing a promising application potential in the field of organic wastewater treatment containing antibiotic contaminants.

Identification and validation of seed dormancy loci and candidate genes and construction of regulatory networks by WGCNA in maize introgression lines.

KEY MESSAGE: Seventeen PHS-QTLs and candidate genes were obtained, including eleven major loci, three under multiple environments and two with co-localization by the other mapping methods; The functions of three candidate genes were validated using mutants; nine target proteins and five networks were filtered by joint analysis of GWAS and WGCNA. Seed dormancy (SD) and pre-harvest sprouting (PHS) affect yield, as well as grain and hybrid quality in seed production. Therefore, identification of genetic and regulatory pathways underlying PHS and SD is key to gene function analysis, allelic variation mining and genetic improvement. In this study, 78,360 SNPs by SLAF-seq of 230 maize chromosome segment introgression lines (ILs), PHS under five environments were used to conduct GWAS (genome wide association study) (a threshold of 1/n), and seventeen unreported PHS QTLs were obtained, including eleven QTLs with PVE > 10% and three QTLs under multiple environments. Two QTL loci were co-located between the other two genetic mapping methods. Using differential gene expression analyses at two stages of grain development, gene functional analysis of Arabidopsis mutants, and gene functional analysis in the QTL region, seventeen PHS QTL-linked candidate genes were identified, and their five molecular regulatory networks constructed. Based on the Arabidopsis T-DNA mutations, three candidate genes were shown to regulate for SD and PHS. Meanwhile, using RNA-seq of grain development, the weighted correlation network analysis (WGCNA) was performed, deducing five regulatory pathways and target genes that regulate PHS and SD. Based on the conjoint analysis of GWAS and WGCNA, four pathways, nine target proteins and target genes were revealed, most of which regulate cell wall metabolism, cell proliferation and seed dehydration tolerance. This has important theoretical and practical significance for elucidating the genetic basis of maize PHS and SD, as well as mining of genetic resources and genetic improvement of traits.

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia.

The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

Clinical efficacy and safety of subcutaneous rituximab in non-Hodgkin lymphoma: a systematic literature review and meta-analysis.

OBJECTIVES: The role of subcutaneous (SC) rituximab in the efficacy and safety to non-Hodgkin lymphoma (NHL) is not clear enough. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the efficacy and safety of subcutaneous rituximab to NHL. METHOD: A full-scale search was carried out based on the set search terms in PubMed, Web of Science, Embase and Cochrane CENTRAL until 12 October 2022 to identify relevant studies of subcutaneous rituximab for NHL. The efficacy and safety outcomes included complete response (CR) plus unconfirmed complete response (CRu), adverse events (AEs), grade ≥3 AEs, serious adverse events (SAEs), administration-related reactions (ARRs), adverse reaction rates. RESULTS: From a total of 758 studies, 9 trials were eligible. The CR/CRu of patients with NHL receiving SC rituximab was 57%, 55% for Diffuse large B-cell lymphoma (DLBCL) and 54% for Follicular lymphoma (FL). The meta-analysis performed on safety demonstrated that AEs of NHL patients with SC rituximab was 85%, grade ≥3 AEs was 38%, SAE was 27% and ARR was 33%. The result also showed that SC rituximab had a high risk of neutropenia and nausea. CONCLUSION: For NHL patients, there is no significant difference in the efficacy between subcutaneous rituximab and conventional therapy, while subcutaneous injection can shorten exposure time in the hospital and reduce the risk of infection.

Chitosan as a biomaterial for the prevention and treatment of dental caries: antibacterial effect, biomimetic mineralization, and drug delivery.

Dental caries is a chronic, progressive disease caused by plaque, influenced by multiple factors and can damage the hard tissues of the teeth. In severe cases, it can also lead to the onset and development of other oral diseases, seriously affecting patients' quality of life. The creation of effective biomaterials for the prevention and treatment of dental caries has become one of the relentless goals of many researchers, with a focus on inhibiting the production of cariogenic plaque and retaining beneficial bacteria, guiding and promoting the reconstruction of dental hard tissues, and delaying the progression of existing caries. Chitosan is a natural cationic polymer extracted from the shells of crustaceans and shellfish. Since its discovery, chitosan has shown to have various biological functions such as antibacterial, biomimetic mineralization, drug delivery, etc., making it one of the most promising biopolymers for new caries prevention and materials of prostheses. Therefore, this article provides an overview of the anti-caries applications of chitosan, which mainly covers the basic research on the application of chitosan in caries prevention and treatment since 2010, with a focus on categorizing and summarizing the following characteristics of chitosan as a caries prevention material, including its antibacterial effect, biomimetic mineralization effect and delivery ability of caries prevention drugs and vaccines. It also explores the limitations of current research on chitosan as a caries prevention biomaterial and the difficulties that need to be focused on and overcome in the future to provide theoretical reference for the clinical implementation of chitosan as a caries prevention biomaterial.

Regulation of secondary hair follicle cycle in cashmere goats by miR-877-3p targeting IGFBP5 gene.

Cashmere, a highly valuable animal product derived from cashmere goats, holds significant economic importance. MiRNAs serve as crucial regulators in the developmental processes of mammalian hair follicles. Understanding the regulation of miRNAs during the hair follicle cycle is essential for enhancing cashmere quality. In this investigation, we employed high-throughput sequencing technology to analyze the expression profiles of miRNAs in the secondary hair follicles of Jiangnan cashmere goats at different stages. Through bioinformatics analysis, we identified differentially expressed miRNAs (DE miRNAs). The regulatory relationships between miRNAs and their target genes were verified using multiple techniques, including RT-qPCR, western blot, Dual-Luciferase Reporter, and CKK-8 assays. Our findings revealed the presence of 193 DE miRNAs during various stages of the hair follicle cycle in Jiangnan cashmere goats. Based on the previously obtained mRNA data, the target genes of DE miRNA were predicted, and 1,472 negative regulatory relationships between DE miRNAs and target genes were obtained. Notably, the expression of chi-miR-877-3p was down-regulated during the telogen (Tn) phase compared to the anagen (An) and catagen (Cn) phases, while the IGFBP5 gene exhibited up-regulation. Further validation experiments confirmed that overexpression of chi-miR-877-3p in dermal papilla cells suppressed IGFBP5 gene expression and facilitated cell proliferation. The results of this study provide novel insights for analyzing the hair follicle cycle.

Cashmere goats, known for their diverse range of animal products including delectable meat, soft sheepskin, and high-quality natural fiber, offer an excellent opportunity to explore hair regeneration as they represent a heterogenous fur mammal. MicroRNAs (miRNAs) are small non-coding RNA molecules encoded by approximately 3% of mammalian genes. Remarkably, they have the ability to regulate around 30% of protein-coding genes. Given that a single miRNA can target multiple genes, they exert control over various biological functions such as metabolism, growth, development, and immunity. In this study, we found that miR-877-3p is able to regulate the expression of insulin-like growth factor binding protein 5 (IGFBP5), a key gene involved in the development of the hair follicle cycle. Investigating the regulatory role of miRNAs in the hair follicle cycle of cashmere goats provides a novel perspective for unraveling the mechanisms underlying hair follicle growth and development in mammals.

Soil-root interface hydraulic conductance determines responses of photosynthesis to drought in rice and wheat.

Rice (Oryza sativa) production consumes a huge amount of fresh water, and improvement of drought tolerance in rice is important to conserve water resources and minimize yield loss under drought. However, processes to improve drought tolerance in rice have not been fully explored, and a comparative study between rice and wheat (Triticum aestivum) is an effective method to understand the mechanisms determining drought tolerance capacity. In the present study, we applied short-term drought stress to Shanyou 63 rice and Yannong 19 wheat to create a range of water potentials and investigated the responses of gas exchange, plant hydraulic conductance, and root morphological and anatomical traits to soil drought. We found that photosynthesis in rice was more sensitive to drought stress than that in wheat, which was related to differences in the decline of stomatal conductance and plant hydraulic conductance (Kplant). The decline of Kplant under drought was mainly driven by the decrease of soil-root interface hydraulic conductance (Ki) because Ki was more sensitive to drought than root and shoot hydraulic conductance and the soil-root interface contributed to >40% of whole-plant hydraulic resistance in both crops. Root shrinkage in response to drought was more severe in rice than that in wheat, which explains the larger depression of Ki and Kplant under drought stress in rice. We concluded that the decline of Ki drives the depression of Kplant and photosynthesis in both crops, and the plasticity of root morphology and anatomy is important in determining drought tolerance capacity.

Correlations between moral courage, moral sensitivity, and ethical decision-making by nurse interns: a cross-sectional study.

BACKGROUND: Clinical decision-making involves ethical issues that become more and more complex. Nurse interns must be more skilled in making rational and timely decisions when facing ethical dilemmas. The contributing factors and their relationships that challenge ethical decision-making among nurse interns must be fully understood, as this level of knowledge can support the development of strategies and interventions that improve the ethical decision-making ability of nurse interns. OBJECTIVE: This study examined the relationships between moral courage, moral sensitivity, and ethical decision-making by nurse interns. In addition, we investigated whether moral sensitivity mediates the relationship between moral courage and ethical decision-making. DESIGN: A descriptive cross-sectional study using an online questionnaire. SETTING: The study sampled nurse interns from Class iii Grade A general hospitals in Sichuan Province, China. PARTICIPANTS: A convenience sampling method was used to select 1334 nurse interns from March 2022 to May 2022. METHODS: A general information questionnaire, the Nurses' Moral Courage Scale (NMCS), the Chinese Moral Sensitivity Questionnaire (MSQ), and the Judgement About Nursing Decision (JAND) were used for data collection. Data was processed and analysed using SPSS 26.0 and Amos 28.0. Data analysis included descriptive statistics, Pearson correlation analysis, and structural equation modelling. RESULTS: Moral courage was found to be positively correlated with ethical decision-making (P < 0.01). Moral sensitivity was also positively correlated with ethical decision-making (P < 0.01) and had a mediating effect on the relationship between moral courage and ethical decision-making (P < 0.01). CONCLUSIONS: The moral courage and moral sensitivity of nurse interns are positively correlated with ethical decision-making ability. Moral sensitivity significantly mediates the relationship between moral courage and ethical decision-making ability. The knowledge gained from this study can inform educational strategies and interventions in supporting the development of nurse interns' ethical decision-making ability.