Turnover intention and its related factors of clinical research coordinator in Hunan, China: a cross-sectional study.

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.

Morphological, Microstructural, and In Situ Chemical Characteristics of Siderite Produced by Iron-Reducing Bacteria.

Dissimilatory iron-reducing bacteria (DIRB) oxidize organic matter or hydrogen and reduce ferric iron to form Fe(II)-bearing minerals, such as magnetite and siderite. However, compared with magnetite, which was extensively studied, the mineralization process and mechanisms of siderite remain unclear. Here, with the combination of advanced electron microscopy and synchrotron-based scanning transmission X-ray microscopy (STXM) approaches, we studied in detail the morphological, structural, and chemical features of biogenic siderite via a growth experiment with Shewanella oneidensis MR-4. Results showed that along with the growth of cells, Fe(II) ions were increasingly released into solution and reacted with CO32- to form micrometer-sized siderite minerals with spindle, rod, peanut, dumbbell, and sphere shapes. They are composed of many single-crystal siderite plates that are fanned out from the center of the particles. Additionally, STXM revealed Fh and organic molecules inside siderite. This suggests that the siderite crystals might assemble around a Fh-organic molecule core and then continue to grow radially. This study illustrates the biomineralization and assembly of siderite by a successive multistep growth process induced by DIRB, also provides evidences that the distinctive shapes and the presence of organic molecules inside might be morphological and chemical features for biogenic siderite.

ERegPose: An explicit regression based 6D pose estimation for snake-like wrist-type surgical instruments.

BACKGROUND: Accurately estimating the 6D pose of snake-like wrist-type surgical instruments is challenging due to their complex kinematics and flexible design. METHODS: We propose ERegPose, a comprehensive strategy for precise 6D pose estimation. The strategy consists of two components: ERegPoseNet, an original deep neural network model designed for explicit regression of the instrument's 6D pose, and an annotated in-house dataset of simulated surgical operations. To capture rotational features, we employ an Single Shot multibox Detector (SSD)-like detector to generate bounding boxes of the instrument tip. RESULTS: ERegPoseNet achieves an error of 1.056 mm in 3D translation, 0.073 rad in 3D rotation, and an average distance (ADD) metric of 3.974 mm, indicating an overall spatial transformation error. The necessity of the SSD-like detector and L1 loss is validated through experiments. CONCLUSIONS: ERegPose outperforms existing approaches, providing accurate 6D pose estimation for snake-like wrist-type surgical instruments. Its practical applications in various surgical tasks hold great promise.

Molecularly imprinted polymers and porous organic frameworks based analytical methods for disinfection by-products in water and wastewater.

Disinfection by-products (DBPs) with heritage toxicity, mutagenicity and carcinogenicity are one kind of important new pollutants, and their detection and removal in water and wastewater has become a common challenge facing mankind. Advanced functional materials with ideal selectivity, adsorption capacity and regeneration capacity provide hope for the determination of DBPs with low concentration levels and inherent molecular structural similarity. Among them, molecularly imprinted polymers (MIPs) are favored, owing to their predictable structure, specific recognition and wide applicability. Also, metal-organic frameworks (MOFs) and covalent-organic frameworks (COFs) with unique pore structure, large specific surface area and easy functionalization, attract increasing interest. Herein, we review recent advances in analytical methods based on the above-mentioned three functional materials for DBPs in water and wastewater. Firstly, MIPs, MOFs and COFs are briefly introduced. Secondly, MIPs, MOFs and COFs as extractants, recognition element and adsorbents, are comprehensively discussed. Combining the latest research progress of solid-phase extraction (SPE), sensor, adsorption and nanofiltration, typical examples on MIPs and MOFs/COFs based analytical and removal applications in water and wastewater are summarized. Finally, the application prospects and challenges of the three functional materials in DBPs analysis are proposed to promote the development of corresponding analytical methods.

Apigenin protects against ischemic stroke by increasing DNA repair.

Background and Objective: Oxidative stress is an important pathological process in ischemic stroke (IS). Apigenin (APG) is a natural product with favorable antioxidative effects, and some studies have already demonstrated the antioxidative mechanism of APG in the treatment of IS. However, the mechanism of APG on DNA damage and repair after IS is not clear. The aim of this study was to investigate the mechanism of APG on DNA repair after IS. Methods: Male Sprague-Dawley rats were used to establish a model of permanent middle cerebral artery occlusion (pMCAO) on one side, and were pre-treated with gavage of APG (30, 60, or 120 mg/kg) for 7 days. One day after pMCAO, the brain tissues were collected. Cerebral infarct volume, brain water content, HE staining and antioxidant index were analyzed to evaluated the brain damage. Molecular Docking, molecular dynamics (MD) simulation, immunohistochemistry, and Western blot were used to explore the potential proteins related to DNA damage repair. Results: APG has a low binding score with DNA repair-related proteins. APG treatment has improved the volume of cerebral infarction and neurological deficits, reduced brain edema, and decreased parthanatos and apoptosis by inhibiting PARP1/AIF pathway. In addition, APG improved the antioxidative capacity through reducing reactive oxygen species and malondialdehyde, and increasing glutathione and superoxide dismutase. Also, APG has reduced DNA damage- and cell death-related proteins such as PARP1, γH2A.X, 53BP1, AIF, cleaved caspase3, Cytochrome c, and increased DNA repair by BRCA1 and RAD51 through homologous recombination repair, and reduced non-homologous end link repair by KU70. Conclusion: APG can improve nerve damage after IS, and these protective effects were realized by reducing oxidative stress and DNA damage, and improving DNA repair.

MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway.

INTRODUCTION: The aim of the study is the regulatory effect of MicroRNA-210 (MiR-210) on cigarette smoke extract (CSE)-induced mouse lung epithelial type II cells (MLE-12) apoptosis and determine whether the MiR-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via Shh signaling pathway. METHODS: Expression of MiR-210 in CSE-induced MLE-12 was assessed by qRT-PCR. The emphysema mouse model and MiR-210 knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vector instillation. The Sonic hedgehog (Shh), Ptch1, Gli1, B-cell lymphoma-2 (Bcl-2), and Caspase 3 protein expressions were detected by Western blotting. mRNA expressions of MiR-210, Shh, Ptch1, and Gli1 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Apoptotic ratios in mice and CSE-induced HPVEC were assessed using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays and flow cytometry. RESULTS: Our results showed that MiR-210 mRNA levels were significantly down-regulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. In vitro, MiR-210 can attenuate the apoptosis of CSE-exposed MLE 12. Moreover, MiR-210 regulated the Shh pathway and promoted its expression. CONCLUSIONS: MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. The present study reveals that MiRNA-210 may be a key regulator of cellular apoptosis and could be explored as a potential therapeutic target in the future.

Synergistic etching of nickel foam by Fe3+ and Cl- ions to synthesize nickel-iron-layered double hydroxide nanolayers with abundant oxygen vacancies for superior urea oxidation.

Urea electrolysis is an appealing topic for hydrogen production due to its ability to extract hydrogen at a lower potential. However, it is plagued by sluggish kinetics and noble-metal catalyst requirements. Herein, we developed nickel-iron-layered double hydroxide (NiFe-LDH) nanolayers with abundant oxygen vacancies (OV) via synergistically etching nickel foam with Fe3+ and Cl- ions, enabling the efficient conversion of urea into H2 and N2. The synthesized OV-NiFe-LDH exhibits a lower potential (1.30 vs. reversible hydrogen electrode, RHE) for achieving 10 mA cm-2 in the urea oxidation reaction (UOR), surpassing most recently reported Ni-based electrodes. OV provides favorable conductivity and a large surface area, which results in a 4.1-fold in electron transport and a 5.1-fold increase in catalyst reactive sites. Density Functional Theory (DFT) calculations indicate that OV can lower the adsorption energy of urea, and enhance the bonding strength of *CONHNH, giving rise to improved UOR. This study provides a viable path toward economical and efficient production of high-purity hydrogen.

Pigmentiphaga kullae CHJ604 improved the growth of tobacco by degrading allelochemicals and xenobiotics in continuous cropping obstacles.

Plant autotoxicity is considered to be one of the important causes of continuous cropping obstacles in modern agriculture, which accumulates a lot of allelochemicals and xenobiotics and is difficult to solve effectively. To overcome tobacco continuous obstacles, a strain Pigmentiphaga kullae CHJ604 isolated from the environment can effectively degrade these compounds in this study. CHJ604 strain can degrade 11 types of autotoxicity allelochemicals and xenobiotics (1646.22 µg/kg) accumulated in the soil of ten-years continuous cropping of tobacco. The 11 allelochemicals and xenobiotics significantly reduced Germination Percentage (GP), Germination Index (GI), and Mean Germination Time (MGT) of tobacco seeds, and inhibited the development of leaves, stems, and roots. These negative disturbances can be eliminated by CHJ604 strain. The degradation pathways of 11 allelochemicals and xenobiotics were obtained by whole genome sequence and annotation of CHJ604 strain. The heterologous expression of a terephthalate 1,2-dioxygenase can catalyze 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 4-hydroxybenzaldehyde, and 4-hydroxy-3-methoxy-benzaldehyde, respectively. The phthalate 4,5-dioxygenase can catalyze phthalic acid, diisobutyl phthalate, and dibutyl phthalate. These two enzymes are conducive to the simultaneous degradation of multiple allelochemicals and xenobiotics by strain CHJ604. This study provides new insights into the biodegradation of autotoxicity allelochemicals and xenobiotics as it is the first to describe a degrading bacterium of 11 types of allelochemicals and xenobiotics and their great potential in improving tobacco continuous obstacles.

The State-of-the-Art and Perspectives of Laser Ablation for Tumor Treatment.

Tumors significantly impact individuals' physical well-being and quality of life. With the ongoing advancements in optical technology, information technology, robotic technology, etc., laser technology is being increasingly utilized in the field of tumor treatment, and laser ablation (LA) of tumors remains a prominent area of research interest. This paper presents an overview of the recent progress in tumor LA therapy, with a focus on the mechanisms and biological effects of LA, commonly used ablation lasers, image-guided LA, and robotic-assisted LA. Further insights and future prospects are discussed in relation to these aspects, and the paper proposed potential future directions for the development of tumor LA techniques.

Stereo attention-based all-in-one super-resolution for robot-assisted minimally invasive surgery.

Robot-assisted minimally invasive surgery (MIS) faces challenges in obtaining high-quality imaging results due to the limited spatial environment. In this paper, we present an all-in-one image super-resolution (SR) algorithm designed to tackle this challenge. By utilizing the stereo information from binocular images, we effectively convert low-resolution images into high-resolution ones. Our model architecture amalgamates the prowess of Convolutional Neural Networks (CNNs) and Transformers, capitalizing on the advantages of both methodologies. To achieve super-resolution across all scale factors, we employ a trainable upsampling module within our proposed network. We substantiate the effectiveness of our method through extensive quantitative and qualitative experiments. The results of our evaluations provide strong evidence supporting the superior performance of our approach in enhancing the quality of surgical images. Our method improves the resolution and thus the overall image quality, which allows the surgeon to perform precise operations conveniently. Simultaneously, it also facilitates the scaling of the region of interest (ROI) to achieve high-quality visualization during surgical procedures. Furthermore, it has the potential to enhance the image quality during telesurgery.

Nuciferine reduces inflammation induced by cerebral ischemia-reperfusion injury through the PI3K/Akt/NF-κB pathway.

BACKGROUND: Cerebral ischemia has the characteristics of high incidence, mortality, and disability, which seriously damages people's health. Cerebral ischemia-reperfusion injury is the key pathological injury of this disease. However, there is a lack of drugs that can reduce cerebral ischemia-reperfusion injury in clinical practice. At present, a few studies have provided some evidence that nuciferine can reduce cerebral ischemia-reperfusion injury, but its specific mechanism of action is still unclear, and further research is still needed. OBJECTIVE: In this study, PC12 cells and SD rats were used to construct OGD/R and MCAO/R models, respectively. Combined with bioinformatics methods and experimental verification methods, the purpose of this study was to conduct a systematic and comprehensive study on the effect and mechanism of nuciferine on reducing inflammation induced by cerebral ischemia-reperfusion injury. RESULTS: Nuciferine can improve the cell viability of PC12 cells induced by OGD/R, reduce apoptosis, and reduce the expression of inflammation-related proteins; it can also improve the cognitive and motor dysfunction of MCAO/R-induced rats by behavioral tests, reduce the area of cerebral infarction, reduce the release of inflammatory factors TNF-α and IL-6 in serum and the expression of inflammation-related proteins in brain tissue. CONCLUSION: Nuciferine can reduce the inflammatory level of cerebral ischemia-reperfusion injury in vivo and in vitro models by acting on the PI3K/Akt/NF-κB signaling pathway, and has the potential to be developed as a drug for the treatment of cerebral ischemia-reperfusion injury.

Portable and Rapid Dual-Biomarker Detection Using Solution-Gated Graphene Field Transistors in the Accurate Diagnosis of Prostate Cancer.

Prostate-specific antigen (PSA) is the common serum-relevant biomarker for early prostate cancer (PCa) detection in clinical diagnosis. However, it is difficult to accurately diagnose PCa in the early stage due to the low specificity of PSA. Herein, a new solution-gated graphene field transistor (SGGT) biosensor with dual-gate for dual-biomarker detection is designed. The sensing mechanism is that the designed aptamers immobilized on the surface of the gate electrodes can capture PSA and sarcosine (SAR) biomolecules and induce the capacitance changes of the electric double layers of SGGT. The limit of detections of PSA and SAR biomarkers can reach 0.01 fg mL-1 , which is three-to-four orders of magnitude lower than previously reported assays. The detection time of PSA and SAR is ≈4.5 and ≈13 min, which is significantly faster than the detection time (1-2 h) of conventional methods. The clinical serum samples testing demonstrates that the biosensor can distinguish the PCa patients from the control group and the diagnosis accuracy can reach 100%. The SGGT biosensor can be integrated into the portable platform and the diagnostic results can directly display on the smartphone/Pad. Therefore, the integrated portable platform of the biosensor can distinguish cancer types through the dual-biomarker detection.

Untethered Microgrippers for Precision Medicine.

Microgrippers, a branch of micro/nanorobots, refer to motile miniaturized machines that are of a size in the range of several to hundreds of micrometers. Compared with tethered grippers or other microscopic diagnostic and surgical equipment, untethered microgrippers play an indispensable role in biomedical applications because of their characteristics such as miniaturized size, dexterous shape tranformation, and  controllable motion, which enables the microgrippers to enter hard-to-reach regions to execute specific medical tasks for disease diagnosis and treatment. To date, numerous medical microgrippers are developed, and their potential in cell manipulation, targeted drug delivery, biopsy, and minimally invasive surgery  are explored. To achieve controlled locomotion and efficient target-oriented actions, the materials, size, microarchitecture, and morphology of microgrippers shall be deliberately designed. In this review, the authors summarizes the latest progress in untethered micrometer-scale grippers. The working mechanisms of shape-morphing and actuation methods for effective movement are first introduced. Then, the design principle and state-of-the-art fabrication techniques of microgrippers are discussed. Finally, their applications in the precise medicine are highlighted, followed by offering future perspectives for the development of untethered medical microgrippers.

Experiences of doctors and nurses offering fertility guidance to young breast cancer patients: A qualitative study.

PURPOSE: Existing qualitative studies on young breast cancer patients' fertility have explored patients' perspectives rather than those of doctors and nurses. With the goal of presenting a scientific basis for the design of high-quality fertility guidance programs, this study examines the advantages and disadvantages of providing fertility guidance, as well as the obstacles perceived by doctors and nurses. METHODS: Purposive sampling was used to select 16 doctors and nurses from a Class III Grade A cancer hospital in Hunan Province, China, from March to May 2023. Face-to-face in-depth interviews were conducted. The interview data were analyzed and organized using Colaizzi's seven-step analysis method and NVivo software, respectively. RESULTS: Three themes and nine sub-themes were extracted from the data: (1) Attitude: maintain patients' fertility hope, respect patients' fertility wishes; (2) Obstacles: patient factors, family factors, healthcare worker factors; (3) Suggestions: enhance the professional confidence of doctors and nurses, ensure two-way communication between doctors and patients, promote interdisciplinary knowledge sharing, and establish a whole-process fertility guidance model. CONCLUSIONS: When carrying out fertility guidance for young breast cancer patients, doctors and nurses should fully respect and safeguard the patients' fertility wishes and hope, continuously strengthen their own knowledge reserve, promote interdisciplinary cooperation and improve their communication abilities, rationally analyze the hindrances, and provide continuous and personalized fertility guidance considering factors related to the patient and their family.

The alternation of halobenzoquinone disinfection byproduct on toxicogenomics of DNA damage and repair in uroepithelial cells.

Halobenzoquinones (HBQs) were recently discovered as an emerging class of drinking water disinfection byproducts with carcinogenic concern. However, the molecular mechanism underlying HBQs-induced DNA damage is not clear. In this study, we integrated in vitro genotoxicity, computational toxicology, and the quantitative toxicogenomic analysis of HBQs on DNA damage/repair pathways in human bladder epithelial cells SV-HUC-1. The results showed that HBQs could induce cytotoxicity with the descending order as 2,6-DIBQ > 2,6-DCBQ ≈ 2,6-DBBQ. Also, HBQs can increase DNA damage in SV-HUC-1 cells and thus generate genotoxicity. However, there is no significant difference in genotoxicity among the three HBQs. The results of molecular docking and molecular dynamics simulation further confirmed that HBQs had high binding fractions and stability to DNA. Toxicogenomic analysis indicated that HBQs interfered with DNA repair pathways, mainly affecting base excision repair, nucleotide excision repair and homologous recombination repair. These results have provided new insights into the underlying molecular mechanisms of HBQs-induced DNA damage, and contributed to the understanding of the relationship between exposure to DBPs and risks of developing bladder cancer.

Development and validation of a fertility information support scale for reproductive-aged patients with breast cancer.

Objective: This study aims to develop and validate a suitable scale for assessing the level of fertility information support in reproductive-aged breast cancer patients. Methods: We utilized an exploratory mixed methods approach, dividing the study into two phases: scale development and validation. In Phase 1, initial items were generated through literature review and qualitative interviews. In Phase 2, a cross-sectional survey was conducted involving 468 reproductive-aged breast cancer patients to evaluate the scale's validity and reliability. Scale items underwent item analysis, and their validity and reliability were assessed using Cronbach's α coefficient, retest reliability, content validity, structural validity, and convergent validity. Results: The final scale comprised 17 items, and exploratory factor analysis revealed three common dimensions with internal consistency coefficients of 0.894, 0.816, and 0.869. The overall internal consistency of the scale was 0.908, with a retest reliability Pearson correlation coefficient of 0.937, indicating strong stability and reliability. The construct validity of the scale was excellent (χ2 = 198.606, df = 113, χ2/df = 1.758, root mean square of approximation error = 0.055, goodness-of-fit index = 0.917, comparative fit index = 0.979, null fitting index = 0.953, and incremental fitting index = 0.979). Conclusions: Our fertility information support scale for reproductive-aged breast cancer patients demonstrates favorable psychometric properties. It serves as a valuable tool for evaluating fertility information support levels among these patients, assisting medical professionals in addressing fertility concerns and implementing personalized support programs. However, further research is needed to investigate the applicability of this scale in patients from diverse social and cultural backgrounds.

Ultrahighly Sensitive and Selective Glutathione Sensor Based on Carbon Dot-Functionalized Solution-Gate Graphene Transistor.

A new type of carbon dot (CD)-functionalized solution-gated graphene transistor (SGGT) sensor was designed and fabricated for the highly sensitive and highly selective detection of glutathione (GSH). The CDs were synthesized via a one-step hydrothermal method using DL-thioctic acid and triethylenetetramine (TETA) as sources of S, N, and C. The CDs have abundant amino and carboxyl groups and were used to modify the surface of the gate electrode of SGGT as probes for detecting GSH. Remarkably, the CDs-SGGT sensor exhibited excellent selectivity and ultrahigh sensitivity to GSH, with an ultralow limit of detection (LOD) of up to 10-19 M. To the best of our knowledge, the sensor outperforms previously reported systems. Moreover, the CDs-SGGT sensor shows rapid detection and good stability. More importantly, the detection of GSH in artificial serum samples was successfully demonstrated.

Resveratrol: a potential medication for the prevention and treatment of varicella zoster virus-induced ischemic stroke.

BACKGROUND: Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular mechanisms of VZV-induced IS are still unclear, and there are no effective agents to treat and prevent VZV-induced IS. OBJECTIVE: By integrating bioinformatics, this study explored the interactions between VZV and IS and potential medication to treat and prevent VZV-induced IS. METHODS: In this study, the VZV and IS datasets from the GEO database were used to specify the common genes. Then, bioinformatics analysis including Gene Ontology, Kyoto Encyclopedia Genes Genomes and Protein-Protein Interaction network analysis was performed. Further, the hub genes, transcription factor (TF) gene interactions, TF-miRNA co-regulatory network and potential drug were obtained. Finally, validation was performed using molecular docking and molecular dynamics simulations. RESULTS: The potential molecular mechanisms of VZV-induced IS were studied using multiple bioinformatics tools. Ten hub genes were COL1A2, DCN, PDGFRB, ACTA2, etc. TF genes and miRNAs included JUN, FOS, CREB, BRCA1, PPARG, STAT3, miR-29, etc. A series of mechanism may be involved, such as inflammation, oxidative stress, blood-brain barrier disruption, foam cell generation and among others. Finally, we proposed resveratrol as a potential therapeutic medicine for the prevention and treatment of VZV-induced IS. Molecular docking and molecular dynamics results showed that resveratrol and hub genes exhibited strong binding score. CONCLUSIONS: Resveratrol could be an alternative for the prevention and treatment of VZV-IS. More in vivo and in vitro studies are needed in the future to fully explore the molecular mechanisms between VZV and IS and for medication development.

Enhancing resilient coping strategies for quality of life in Chinese adult children caregiving for parents with advanced cancer: a cross-sectional study.

PURPOSE: This study investigated the mediating role of individual resilience in the relationship between caregiver burden and quality of life (QoL) among Chinese adult children providing care to their parents with advanced cancer, with the aim to inform effective coping strategies and positive caregiving outcomes. METHODS: In a cross-sectional design, 614 caregivers from multiple centers, whose parents were undergoing chemotherapy and/or radiotherapy, completed questionnaires encompassing demographics, caregiver burden, symptoms of anxiety and depression, resilience, and QoL. RESULTS: Findings revealed a moderate level of caregiver burden among participants, significantly influenced by factors including education level, family income, single-child status, and participation in social media patient support groups. Caregivers who were only children or involved in patient support groups reported higher burden. Importantly, path analysis showed a significant impact of caregiver burden, anxiety, and depression on QoL, with these relationships being mediated by individual resilience. CONCLUSIONS: Chinese adult child caregivers face a considerable burden, negatively influencing their QoL. Individual resilience, a modifiable factor, was identified as a critical mediator in this relationship, mitigating the negative implications of caregiver burden, anxiety, and depression. These findings underscore the need for caregiver interventions that consider not only demographics but also the socio-psychological dynamics of caregiving to enhance caregiver QoL.

Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection.

Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloid isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to investigate the effect of γ-Fagarine on hMPV infection and explore its underlying molecular mechanisms. Vero-E6 and 16HBE cells were used as cell models. Virus replication and microcosm character were explored in Vero-E6 cells. Then, the antiviral activities were investigated by quantitative real-time PCR (RT-qPCR), western blotting (WB), and indirect immunofluorescence assays (IFAs) in Vero-E6 and 16HBE. Potential mechanisms of γ-Fagarine related to HSPG and lysosome pH were assessed in 16HBE cells. Lastly, a virus-infected mouse model was established and antiviral assay in vivo was conducted. γ-Fagarine showed no toxicity toward Vero-E6 cells and 16HBE cells but demonstrated anti-hMPV activity. Virus titers of γ-Fagarine group were reduced to 33% and 45% of the hMPV groups, respectively. Besides, mechanistic studies revealed that γ-Fagarine could inhibit hMPV by dual mechanisms of direct restraining virus binding with HSPG and influencing lysosome pH. Furthermore, oral delivery of γ-Fagarine to hMPV-infected mice at a dosage of 25 mg/kg reduced the hMPV load in lung tissues. After γ-Fagarine treatment, pathological damage caused by viral infection was also ameliorated. These findings suggest that γ-Fagarine has antiviral effects in vitro and in vivo, which are associated with its ability to restrain virus binding with HSPG and influence lysosome pH, thus indicating that γ-Fagarine has the potential to serve as a candidate to fight against hMPV infection and other respiratory viruses such as influenza viruses and SARS-CoV-2.