Assessing the mediating role of family resilience between caregiver burden and caregiver capacity: a cross-sectional study among Chinese stroke survivors and family caregivers in a real-world setting.

OBJECTIVES: To investigate the relationships among caregiver burden, family resilience, and caregiver capacity in the care of stroke survivors. We hypothesised that family resilience would mediate the relationship between caregiver burden and caregiver capacity. DESIGN: A cross-sectional study design was used. SETTING: The study was conducted in a tertiary care setting in Ningbo City, Zhejiang Province, China. PARTICIPANTS: The study involved 413 stroke survivors and their primary caregivers. OUTCOME MEASURES: The primary caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale, Zarit Caregiver Burden Interview and Family Caregiver Task Inventor and provided their sociodemographic information. Stroke survivors were assessed for activities of daily living, and their sociodemographic information was provided. Data were analysed, controlling for sociodemographic variables and focusing on the mediating effect of family resilience. RESULTS: Caregiver burden was influenced by the activities of daily living of stroke survivors, caregiver age and caregiver health status (p<0.05). Higher caregiver burden was associated with lower family resilience (p<0.01). Lower caregiver capacity corresponded to heavier caregiver burden (p<0.01). Family resilience mediated the relationship between caregiver burden and caregiver capacity (b=0.1568; 95% CI: 0.1063 to 0.2385). CONCLUSIONS: Enhancing family resilience can reduce caregiver burden and improve caregiver capacity in stroke care. These findings underscore the importance of developing interventions focused on nursing skills and family resilience.

Estrogen inhibits TGF­ß1­stimulated cardiac fibroblast differentiation and collagen synthesis by promoting Cdc42.

17ß­estradiol (E2) can inhibit cardiac fibrosis in female patients with heart failure (HF) and activate cell division cycle 42 (Cdc42), however it is unknown whether 17ß­estradiol (E2) can ameliorate differentiation and collagen synthesis in TGF­ß1­stimulated mouse cardiac fibroblasts (MCFs) by regulating cell division cycle 42 (Cdc42). The present study aimed to investigate the roles of estrogen and Cdc42 in preventing myocardial fibrosis and the underlying molecular mechanisms. An ELISA was used to measure the levels of E2 and Cdc42 in the serum of patients with heart failure (HF), and western blotting was used to measure the expression levels of Cdc42 in TGF­ß1­stimulated immortalized MCFs. MCFs were transfected with a Cdc42 overexpression (OE) lentivirus or small interfering RNA (siRNA), or treated with a Cdc42 inhibitor (MLS­573151), and the function of Cdc42 was assessed by western blotting, immunofluorescence staining, reverse transcription­quantitative PCR and dual­luciferase reporter assays. Western blotting and immunofluorescence staining were performed to verify the protective effect of E2 on TGF­ß1­stimulated MCFs, and the association between the protective effect and Cdc42. The results demonstrated that Cdc42 levels were increased in the serum of patients with HF and were positively correlated with the levels of E2; however, Cdc42 levels were decreased in TGF­ß1­stimulated MCFs. Cdc42 inhibited MCF differentiation and collagen synthesis, as indicated by the protein expression of α­smooth muscle actin, collagen I and collagen III. Mechanistically, Cdc42 inhibited the transcription of TGF­ß1 by promoting the expression of p21 (RAC1)­activated kinase 1 (Pak1)/JNK/c­Jun signaling pathway proteins and inhibiting the activity of the Tgfb1 gene promoter. In addition, E2 inhibited the differentiation and collagen synthesis of TGF­ß1­stimulated MCFs, and promoted the protein expression of Pak1, JNK and c­Jun, consistent with the effects of Cdc42, whereas the effects of E2 were abolished when Cdc42 was knocked down. The aforementioned findings suggested that E2 could inhibit differentiation and collagen synthesis in TGF­ß1­stimulated MCFs by regulating Cdc42 and the downstream Pak1/JNK/c­Jun signaling pathway.

Surfactant-Dependent Partitioning of Organics in Aqueous-Organic Reaction Systems.

A fluorescence lifetime imaging microscopy (FLIM) technique characterizes surfactant-dependent partitioning of organics in a system that mimics a Negishi-like cross-coupling reaction in water, under synthetic concentrations, with emulsion droplets. Experimental partitioning data were not predictable from simple hydrophilic-lipophilic balances. The ionic surfactant cetrimonium chloride suppressed the reactivity of the metallic zinc surface, presumably through competitive chloride binding and concurrent cetrimonium coating, a finding that may contribute to the reduced performance of ionic surfactants in the bench-scale coupling reaction.

Clinical characteristics and risk factors of connective tissue disease complicated with bronchiectasis and pulmonary infection.

The clinical data from 118 CTD patients with bronchiectasis were collected and categorized into two groups: pulmonary infection present (n = 67) and absent (n = 51), for comparative analysis of characteristics and risk factors. Then, we analyzed and compared their demographics, disease characteristics, and risk factors for infection. Among the whole cohort (n = 118), the incidence of pulmonary infections was 56.78%. The occurrence of rheumatoid arthritis, systemic lupus erythematosus, and vasculitis was found to be associated with an increased risk of pulmonary infection. Sputum culture identified Pseudomonas aeruginosa and Klebsiella pneumoniae as the predominant pathogens in the infected group. Notably, symptoms such as joint pains (p = 0.018) and morning stiffness (p = 0.017) were significantly more common in the infected group compared to the noninfected group. Moreover, our findings revealed that elevated levels of C-reactive protein and complement C3, along with bronchial expansion observed on high-resolution computed tomography (HRCT), were significant independent factors in the infection group. Conversely, pulmonary interstitial changes identified through HRCT (OR: 0.135, 95% CI: 0.030-0.612, p = 0.009) were significantly associated with the non-infection group. Overall, this study provides valuable insights into managing CTD patients with bronchiectasis, emphasizing early detection and tailored approaches to prevent and treat pulmonary infections for better outcomes.

Pollution characteristics, distribution and risk level of heavy metals in sediments of the Yangtze River estuary.

Pollution characteristics, distribution, risk and sources of 7 heavy metals in sediments of Yangtze River Estuary were investigated. Total concentration ranges of As, Cr, Cu, Cd, Pb, Zn and Ni were [0, 16.5], [1.48, 51.3], [2.66, 318], [0, 0.99], [35.6, 992], [8, 91.3] and [1.88, 108] mg/kg, respectively. Based on the potential ecological risk index and Geoaccumulation index, it was determined that Pb is the most polluted heavy metal. According to class I standard of "Marine sediment quality" of China, mean baseline levels multiples were Pb (8.34) > Cu (0.57) > Cr (0.37) > Zn (0.355) > Ni (0.352) > As (0.28) > Cd (0.00). The study also found the heavy metal content of Pb is the most serious, but most of the Pb content comes from the residual state, which has minimal impact on the environment. The East Nanhui Shoal was identified as the most polluted sub-area in terms of Pb pollution, followed by other specific locations. Considering the pollution level and transport costs, the study concluded that dredge soils of the Yangtze River Estuary Deepwater Channel are not suitable for the restoration of East Hengsha Shoal.

ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores.

Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.

The value of low-intensity pulsed ultrasound in reducing ovarian injury caused by chemotherapy in mice.

BACKGROUND: Ovarian damage and follicle loss are major side effects of chemotherapy in young female patients with cancer. However, effective strategies to prevent these injuries are still lacking. The purpose of this study was to verify low-intensity pulsed ultrasound (LIPUS) can reduce ovarian injury caused by chemotherapy and to explore its underlying mechanisms in mice model. METHODS: The mice were randomly divided into the Control group, Cisplatin group, and Cisplatin + LIPUS group. The Cisplatin group and Cisplatin + LIPUS group were intraperitoneally injected with cisplatin every other day for a total of 10 injections, and the Control group was injected with saline. On the second day of each injection, the Cisplatin + LIPUS group received irradiation, whereas the other two groups received sham irradiation. We used a variety of biotechnologies to detect the differences in follicle count, granulosa cell apoptosis, fibrosis, transcriptome level, oxidative damage, and inflammation in differently treated mice. RESULT: LIPUS was able to reduce primordial follicle pool depletion induced by cisplatin and inhibit the apoptosis of granulosa cells. Transcriptomic results confirmed that LIPUS can reduce ovarian tissue injury. We demonstrated that LIPUS can relieve ovarian fibrosis by inhibiting TGF-ß1/Smads pathway. Meanwhile, it can reduce the oxidative damage and reduced the mRNA levels of proinflammatory cytokines caused by chemotherapy. CONCLUSION: LIPUS can reduce the toxic effects of chemotherapy drugs on ovaries, inhibit ovarian fibrosis, reduce the inflammatory response, and redcue the oxidative damage, reduce follicle depletion and to maintain the number of follicle pools.

Discovery of a novel SHP2 allosteric inhibitor using virtual screening, FMO calculation, and molecular dynamic simulation.

CONTEXT: SHP2 is a non-receptor protein tyrosine phosphatase to remove tyrosine phosphorylation. Functionally, SHP2 is an essential bridge to connect numerous oncogenic cell-signaling cascades including RAS-ERK, PI3K-AKT, JAK-STAT, and PD-1/PD-L1 pathways. This study aims to discover novel and potent SHP2 inhibitors using a hierarchical structure-based virtual screening strategy that combines molecular docking and the fragment molecular orbital method (FMO) for calculating binding affinity (referred to as the Dock-FMO protocol). For the SHP2 target, the FMO method prediction has a high correlation between the binding affinity of the protein-ligand interaction and experimental values (R2 = 0.55), demonstrating a significant advantage over the MM/PBSA (R2 = 0.02) and MM/GBSA (R2 = 0.15) methods. Therefore, we employed Dock-FMO virtual screening of ChemDiv database of ∼2,990,000 compounds to identify a novel SHP2 allosteric inhibitor bearing hydroxyimino acetamide scaffold. Experimental validation demonstrated that the new compound (E)-2-(hydroxyimino)-2-phenyl-N-(piperidin-4-ylmethyl)acetamide (7188-0011) effectively inhibited SHP2 in a dose-dependent manner. Molecular dynamics (MD) simulation analysis revealed the binding stability of compound 7188-0011 and the SHP2 protein, along with the key interacting residues in the allosteric binding site. Overall, our work has identified a novel and promising allosteric inhibitor that targets SHP2, providing a new starting point for further optimization to develop more potent inhibitors. METHODS: All the molecular docking studies were employed to identify potential leads with Maestro v10.1. The protein-ligand binding affinities of potential leads were further predicted by FMO calculations at MP2/6-31G* level using GAMESS v2020 system. MD simulations were carried out with AmberTools18 by applying the FF14SB force field. MD trajectories were analyzed using VMD v1.9.3. MM/GB(PB)SA binding free energy analysis was carried out with the mmpbsa.py tool of AmberTools18. The docking and MD simulation results were visualized through PyMOL v2.5.0.

Machine learning in nanozymes: from design to application.

Nanozymes, a distinctive class of nanomaterials endowed with enzyme-like activity and kinetics akin to enzyme-catalysed reactions, present several advantages over natural enzymes, including cost-effectiveness, heightened stability, and adjustable activity. However, the conventional trial-and-error methodology for developing novel nanozymes encounters growing challenges as research progresses. The advent of artificial intelligence (AI), particularly machine learning (ML), has ushered in innovative design approaches for researchers in this domain. This review delves into the burgeoning role of ML in nanozyme research, elucidating the advancements achieved through ML applications. The review explores successful instances of ML in nanozyme design and implementation, providing a comprehensive overview of the evolving landscape. A roadmap for ML-assisted nanozyme research is outlined, offering a universal guideline for research in this field. In the end, the review concludes with an analysis of challenges encountered and anticipates future directions for ML in nanozyme research. The synthesis of knowledge in this review aims to foster a cross-disciplinary study, propelling the revolutionary field forward.

Thyroid Metastases from Breast Cancer Case Report and Literature Review.

BACKGROUND: Thyroid metastasis arising from primary breast cancer is a rare phenomenon, with only a handful of cases documented in both national and international literature. The management approach and prognosis of this occurrence have sparked debates and uncertainties. CASE PRESENTATION: Herein, we report the case of a 55-year-old woman with breast cancer. She previously underwent extensive excision of the breast lesion with adjuvant chemotherapy and endocrine therapy. After 9 years, she presented with neck discomfort and examination suggested right thyroid metastasis and lymph node metastasis in the neck. Imaging showed pulmonary and bone metastases. Furthermore, the patient received endocrine therapy. After 7 months of follow- up, the patient survived without any new distant metastases. Thyroid metastases originating from breast cancer often unfold with a subtle, intricate nature, making early detection challenging. They tend to emerge inconspicuously, intertwining with widespread systemic metastases, hinting at a less favorable prognosis. CONCLUSION: Given the unusual clinical indicators, identifying heterochronic thyroid metastases in patients with tumors poses a distinct challenge, requiring clinicians to navigate the follow-up process with heightened sensitivity. The key lies in timely detection and early intervention, factors that can significantly enhance the overall quality of life for patients.

TMEM16A inhibits renal tubulointerstitial fibrosis via Wnt/ß-catenin signaling during hypertension nephropathy.

BACKGROUND AND OBJECTIVE: Hypertensive nephropathy is the second leading cause of end-stage renal disease, but its underlying pathogenesis remains unclear. Therefore, this study aimed to explore whether transmembrane protein 16 A (TMEM16A), the molecular basis of calcium-activated chloride channels (CaCC), is involved in the development and progression of hypertensive nephropathy. METHODS: In vivo and in vitro experiments were conducted using a hypertensive murine model and human kidney proximal tubular epithelial cells (HK-2 cells), respectively. EXPERIMENTAL RESULTS: The expression of TMEM16A was down-regulated in renal samples of hypertensive nephropathy patients and hypertensive model mice, accompanied by excessive deposition of extracellular matrix proteins (ECM) such as Fibronectin, Laminin, Collagen I and Collagen III, the up-regulation of α-smooth muscle actin (α-SMA) expression, and the decrease of E-cadherin. Overexpression of TMEM16A or knockdown of TMEM16A inhibited or promoted the expression of Wnt/ß-catenin signaling pathway proteins Wnt3a, LRP5 and active ß-catenin in HK-2 cells, preventing the epithelial-to-mesenchymal transition (EMT) of renal tubules, and the synthesis of ECM components. CONCLUSION: In angiotensin II (Ang II)-induced hypertensive nephropathy, TMEM16A was identified as a key player inhibiting the detrimental changes in renal tubules, suggesting a potential avenue for mitigating renal damage in hypertensive nephropathy.

Effect of Particle Size and Hydrophobicity on Bubble-Particle Collision Detachment at the Slurry-Foam Phase Interface.

The slurry phase, foam phase, and slurry-foam phase interfaces are the typical locations for bubble-particle detachment, and significant advancements have been achieved in the detachment theory of the slurry phase and foam phase. However, the microscopic detachment mechanism of particles at the slurry-foam phase interface is still unclear. Specifically, there is still debate concerning the collision detachment mechanism of bubble-particle aggregates. Thus, this work investigated the effects of particle size and hydrophobicity on bubble-particle collision detachment. First, a tensiometer detected the detachment force between particles and bubbles. Next, using a high-speed dynamic camera, the collision detachment probability and detachment behavior of bubble-particle aggregates at the interface (solid surface) were statistically recorded and captured. Last, MATLAB software was used to analyze the trajectory and velocity of the particles and the velocity and projected area of the bubbles in the process of bubble-particle collision detachment. This allows for a deeper investigation of the mechanism underlying the detachment of particles of various sizes and hydrophobicity. It is discovered that as particle hydrophobicity increases, the probability of bubble-particle collision detachment reduces. This is because when particle hydrophobicity increases, so does the interaction force between particles and bubbles, improving the stability of the bubble-particle aggregates. Simultaneously, it is discovered that there are notable differences in the collision detachment mechanisms of various particle sizes. Due to their low gravity, the fine particles in the bubble-particle aggregate will slide down the bubble's surface when it collides with the solid surface. This differential velocity motion between the particle and the bubble plays a significant role in the fine particles' detachment. However, the gravity of the coarse particles is strong enough to squeeze the bubbles vertically, and bubble oscillation is an important reason for the detachment of the bubble-particle aggregates. The study's findings advance our understanding of the bubble-particle collision detachment mechanism and offer a theoretical direction for investigating collision detachment behavior at the real slurry-foam phase interface.

Subcutaneous injection of hyaluronic acid leading to emboliom and recanalization process monitored in real time by three-dimensional photoacoustic imaging.

This study describes a method for real-time examination of the microvascular system based on the three-dimensional photoacoustic imaging system to prevent arterial complications, especially vascular embolism, during hyaluronic acid (HA) injections. Chicken embryos were used to simulate the superficial blood vessels of human skin, and then the target area was imaged by the photoacoustic imaging system for three-dimensional vascular imaging, and then the syringe and blood vessels were monitored, and the syringe angle and penetration depth were adjusted in time using an injection device to avoid puncturing the arterial vasculature and clogging the blood vessels. HA was then injected into smaller vessels on the dorsum of the tongue in mice and into thicker vessels on the dorsal portion of the tongue in rats to mimic embolization, and the post-operative recovery was reflected by the changes in the pixel dots of the extracted part of the blocked blood vessels, and it was observed that the blood flow in the area of the fine vessels was restored in about 3 days, whereas blood flow in the area of the large vessels was restored in only about 1 h. The method presented in this paper allows precise guidance of injectable filler HA, which has good application prospects in improving the safety of injection micro-plastic surgery and reducing the experience requirements for medical personnel.

Pandemic fatigue and clinical front-line medical staff health, job status during the COVID-19 pandemic: A cross-sectional survey after the lifting of epidemic restrictions.

AIM: This study aimed to measure pandemic fatigue, physical and mental health, and job status of front-line medical staff in Ningbo. And to identify factors associated with pandemic fatigue. BACKGROUND: There was an acute increase in fatigue symptoms at the COVID-19 pandemic onset. The front-line medical staff is particularly vulnerable to fatigue due to their high-intensity work. DESIGN: This was a descriptive, cross-sectional study conducted using an online survey that included demographic data, investigation of COVID-19 history and job status. The Fatigue Assessment Scale, GAD-7 score and Sleep Quality Scale were used to collect data from 479 front-line medical staff. METHODS: The study involved 479 front-line medical staff in Ningbo, China. The survey was conducted using an online questionnaire that included demographic data, investigation of COVID-19 history and job status. The Fatigue Assessment Scale, GAD-7 score and Sleep Quality Scale were used to collect data. RESULTS: The results showed that of the 479 participants, 393 (82%) reported pandemic fatigue, 393 (82%) reported job satisfaction and 433 (90.4%) identified with their sense of job value. Sleep quality, work with a fever, economic subsidies for fighting COVID-19 and recognizing professional value were significantly correlated with pandemic fatigue. CONCLUSIONS: As the COVID-19 pandemic challenges front-line medical workers, implementing measures is essential. Health policy implementers could provide sufficient front-line medical staff to ensure rest in case of infection, promote sleep quality and foster professional value and financial subsidies in units. RELEVANCE TO CLINICAL PRACTICE: The study shows how pandemic fatigue affects front-line medical staff during the COVID-19 pandemic and suggests measures to support them, including promoting sleep quality, providing rest for infected staff, fostering professional value and financial subsidies. The recommendations are relevant to clinical practice as they help support medical staff and ensure high-quality care for patients during the pandemic. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. Not applicable.

Metformin protects ovarian granulosa cells in chemotherapy-induced premature ovarian failure mice through AMPK/PPAR-γ/SIRT1 pathway.

Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs). Our findings demonstrate that intragastric administration of MET ameliorates ovarian damage and alleviates hormonal disruption in chemotherapy-induced POF mice. This effect is achieved through the reduction of inflammatory and oxidative stress-related harm. Additionally, MET significantly relieves abnormal inflammatory response, ROS accumulation, and senescence in primary GCs co-cultured with M1 macrophages. We also observed that this protective role of MET is closely associated with the AMPK/PPAR-γ/SIRT1 pathway in cell models. In conclusion, our results suggest that MET can protect against chemotherapy-induced ovarian injury by inducing the expression of the AMPK pathway while reducing oxidative damage and inflammation.

Nondestructive and high-resolution monitoring of inflammation-type skull defects regeneration on adult zebrafish with optical coherence tomography.

Optimized animal models and effective imaging techniques are exceedingly important to study cranial defects in bone loss due to chronic inflammation. In this study, the assessment procedure on a zebrafish inflammation-type skull defects model was monitored in vivo with spectral-domain optical coherence tomography (SD-OCT), and the efficacy of etidronate disodium in bone regeneration was assessed. An acute skull defect injury model was established in adult zebrafish using a stereotaxic craniotomy device. SD-OCT imaging was performed immediately following the mechanical injury. Both SD-OCT and immunohistochemistry results demonstrated an increase in inflammation-induced skull destruction within 5 days, which was confirmed by pathological experiments.

Thorough Optimization for Intrinsically Stretchable Organic Photovoltaics.

The development of intrinsically stretchable organic photovoltaics (is-OPVs) with a high efficiency is of significance for practical application. However, their efficiencies lag far behind those of rigid or even flexible counterparts. To address this issue, an advanced top-illuminated OPV is designed and fabricated, which is intrinsically stretchable and has a high performance, through systematic optimizations from material to device. First, the stretchability of the active layer is largely increased by adding a low-elastic-modulus elastomer of styrene-ethylene-propylene-styrene tri-block copolymer (SEPS). Second, the stretchability and conductivity of the opaque electrode are enhanced by a conductive polymer/metal (denoted as M-PH1000@Ag) composite electrode strategy. Third, the optical and electrical properties of a sliver nanowire transparent electrode are improved by a solvent vapor annealing strategy. High-performance is-OPVs are successfully fabricated with a top-illuminated structure, which provides a record-high efficiency of 16.23%. Additionally, by incorporating 5-10% elastomer, a balance between the efficiency and stretchability of the is-OPVs is achieved. This study provides valuable insights into material and device optimizations for high-efficiency is-OPVs, with a low-cost production and excellent stretchability, which indicates a high potential for future applications of OPVs.

Choosing the right animal model for osteomyelitis research: Considerations and challenges.

Osteomyelitis is a debilitating bone disorder characterized by an inflammatory process involving the bone marrow, bone cortex, periosteum, and surrounding soft tissue, which can ultimately result in bone destruction. The etiology of osteomyelitis can be infectious, caused by various microorganisms, or noninfectious, such as chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). Researchers have turned to animal models to study the pathophysiology of osteomyelitis. However, selecting an appropriate animal model that accurately recapitulates the human pathology of osteomyelitis while controlling for multiple variables that influence different clinical presentations remains a significant challenge. In this review, we present an overview of various animal models used in osteomyelitis research, including rodent, rabbit, avian/chicken, porcine, minipig, canine, sheep, and goat models. We discuss the characteristics of each animal model and the corresponding clinical scenarios that can provide a basic rationale for experimental selection. This review highlights the importance of selecting an appropriate animal model for osteomyelitis research to improve the accuracy of the results and facilitate the development of novel treatment and management strategies.

Chromosome-scale genome of the human blood fluke Schistosoma mekongi and its implications for public health.

BACKGROUND: Schistosoma mekongi is a human blood fluke causing schistosomiasis that threatens approximately 1.5 million humans in the world. Nonetheless, the limited available S. mekongi genomic resources have hindered understanding of its biology and parasite-host interactions for disease management and pathogen control. The aim of our study was to integrate multiple technologies to construct a high-quality chromosome-level assembly of the S. mekongi genome. METHODS: The reference genome for S. mekongi was generated through integrating Illumina, PacBio sequencing, 10 × Genomics linked-read sequencing, and high-throughput chromosome conformation capture (Hi-C) methods. In this study, we conducted de novo assembly, alignment, and gene prediction to assemble and annotate the genome. Comparative genomics allowed us to compare genomes across different species, shedding light on conserved regions and evolutionary relationships. Additionally, our transcriptomic analysis focused on genes associated with parasite-snail interactions in S. mekongi infection. We employed gene ontology (GO) enrichment analysis for functional annotation of these genes. RESULTS: In the present study, the S. mekongi genome was both assembled into 8 pseudochromosomes with a length of 404 Mb, with contig N50 and scaffold N50 lengths of 1168 kb and 46,759 kb, respectively. We detected that 43% of the genome consists of repeat sequences and predicted 9103 protein-coding genes. We also focused on proteases, particularly leishmanolysin-like metalloproteases (M8), which are crucial in the invasion of hosts by 12 flatworm species. Through phylogenetic analysis, it was discovered that the M8 gene exhibits lineage-specific amplification among the genus Schistosoma. Lineage-specific expansion of M8 was observed in blood flukes. Additionally, the results of the RNA-seq revealed that a mass of genes related to metabolic and biosynthetic processes were up-regulated, which might be beneficial for cercaria production. CONCLUSIONS: This study delivers a high-quality, chromosome-scale reference genome of S. mekongi, enhancing our understanding of the divergence and evolution of Schistosoma. The molecular research conducted here also plays a pivotal role in drug discovery and vaccine development. Furthermore, our work greatly advances the understanding of host-parasite interactions, providing crucial insights for schistosomiasis intervention strategies.