Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic network analysis of human immunodeficiency virus sexual transmission in rural Southwest China after the expansion of antiretroviral therapy: A population-based study

Background This study is used to analyze the genetic network of HIV sexual transmission in rural areas of Southwest China after expanding antiretroviral therapy (ART) and to investigate the factors associated with HIV sexual transmission through the genetic network. Materials and methods This was a longitudinal genetic network study in Guangxi, China. The baseline survey and follow-up study were conducted among patients with HIV in 2015, and among those newly diagnosed from 2016 to 2018, respectively. A generalized estimating equation model was employed to explore the factors associated with HIV transmission through the genetic linkage between newly diagnosed patients with HIV (2016–2018) and those at baseline (2015–2017), respectively. Results Of 3,259 identified HIV patient sequences, 2,714 patients were at baseline, and 545 were newly diagnosed patients with HIV at follow-up. A total of 8,691 baseline objectives were observed by repeated measurement analysis. The prevention efficacy in HIV transmission for treated HIV patients was 33% [adjusted odds ratio (AOR): 0.67, 95% confidence interval (CI): 0.48–0.93]. Stratified analyses indicated the prevention efficacy in HIV transmission for treated HIV patients with a viral load (VL) of <50 copies/ml and those treated for 4 years with a VL of <50 copies/ml to be 41 [AOR: 0.59, 95% CI: 0.43–0.82] and 65% [AOR: 0.35, 95% CI: 0.24–0.50], respectively. No significant reduction in HIV transmission occurred among treated HIV patients with VL missing or treated HIV patients on dropout. Some factors were associated with HIV transmission, including over 50 years old, men, Zhuang and other nationalities, with less than secondary schooling, working as a farmer, and heterosexual transmission. Conclusion This study reveals the role of ART in reducing HIV transmission, and those older male farmers with less than secondary schooling are at high risk of HIV infection at a population level. Improvements to ART efficacy for patients with HIV and precision intervention on high-risk individuals during the expansion of ART are urgently required.
Sleep pattern in relation to recurrent osteoporotic fracture in the elderly

Background Previous studies assessed the relationship between individual sleep behavior and fracture risk, rather than taking into account the joint complexity of the sleep behaviors. We aimed to explore the association between sleep pattern and risk of imminent recurrent osteoporotic fracture in older hospitalized patients due to an index osteoporotic fracture, where sleep pattern was evaluated as a combination incorporating five common sleep behaviors (i.e., insomnia, snoring, nocturnal sleep duration, daytime napping, and midnight waking up). Methods We used data from a prospective cohort study for analyses. Patients who aged not < 55 years and were admitted to the hospital due to an index osteoporotic fracture were recruited. Sleep pattern was grouped as healthy, intermediate, and poor pattern, based on the categorization of overall sleep scores. We used Cox proportional hazard models to explore sleep pattern in relation to imminent recurrent fracture. Results We included a total of 185 elderly hospitalized patients for analyses with mean (± standard deviation) age = 71.5 ± 10.3 years and 87.0% female. During a mean follow-up of 14.7 months, there were 10 (5.4%) recurrent osteoporotic fractures observed. A significantly higher overall sleep score was found in patients with recurrent fractures when compared with those without fractures (3.20 vs. 2.36, p = 0.038). Both intermediate (p = 0.76) and poor sleep patterns (p = 0.093) were non–significantly associated with an elevated risk of fracture when compared with a healthy pattern. Per-one-increase in the overall sleep score was significantly related to an increased risk of fracture: hazard ratio = 1.60 (95% confidence interval: 1.00-−2.55) from the multivariable model. Conclusion Per-one-increase in the overall sleep score was found to be significantly associated with a 60% higher risk of imminent recurrent osteoporotic fracture in the elderly, and intermediate and poor sleep patterns were non–significantly related to an increased risk of recurrent fracture. More high-quality evidence is required to further evaluate the relationship between the sleep pattern and the risk of recurrent osteoporotic fracture in the elderly.
Cuproptosis status affects treatment options about immunotherapy and targeted therapy for patients with kidney renal clear cell carcinoma

The development of immunotherapy has changed the treatment landscape of advanced kidney renal clear cell carcinoma (KIRC), offering patients more treatment options. Cuproptosis, a novel cell death mode dependent on copper ions and mitochondrial respiration has not yet been studied in KIRC. We assembled a comprehensive cohort of The Cancer Genome Atlas (TCGA)-KIRC and GSE29609, performed cluster analysis for typing twice using seven cuproptosis-promoting genes (CPGs) as a starting point, and assessed the differences in biological and clinicopathological characteristics between different subtypes. Furthermore, we explored the tumor immune infiltration landscape in KIRC using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) and the potential molecular mechanisms of cuproptosis in KIRC using enrichment analysis. We constructed a cuproptosis score (CUS) using the Boruta algorithm combined with principal component analysis. We evaluated the impact of CUS on prognosis, targeted therapy, and immunotherapy in patients with KIRC using survival analysis, the predictions from the Cancer Immunome Atlas database, and targeted drug susceptibility analysis. We found that patients with high CUS levels show poor prognosis and efficacy against all four immune checkpoint inhibitors, and their immunosuppression may depend on TGFB1. However, the high-CUS group showed higher sensitivity to sunitinib, axitinib, and elesclomol. Sunitinib monotherapy may reverse the poor prognosis and result in higher progression free survival. Then, we identified two potential CPGs and verified their differential expression between the KIRC and the normal samples. Finally, we explored the effect of the key gene FDX1 on the proliferation of KIRC cells and confirmed the presence of cuproptosis in KIRC cells. We developed a targeted therapy and immunotherapy strategy for advanced KIRC based on CUS. Our findings provide new insights into the relationship among cuproptosis, metabolism, and immunity in KIRC.
The relationship of maternal and child methylation of the glucocorticoid receptor NR3C1 during early childhood and subsequent child psychopathology at school-age in the context of maternal interpersonal violence-related post-traumatic stress disorder

Introduction Interpersonal violent (IPV) experiences when they begin in childhood and continue in various forms during adulthood often lead to chronic post-traumatic stress disorder (PTSD) that is associated in multiple studies with hypocortisolism and lower percentage of methylation of the promoter region of the gene coding for the glucocorticoid receptor (NR3C1). This prospective, longitudinal study examined the relationship of NR3C1 methylation among mothers with IPV-related PTSD and their toddlers and then looked at the relationship of maternal NR3C1 methylation and child psychopathology at school age. Methods Forty-eight mothers were evaluated for life-events history and post-traumatic stress disorder via structured clinical interview when their children were ages 12–42 months (mean age 26.7 months, SD 8.8). Their children's psychopathology in terms of internalizing symptoms and externalizing behaviors was evaluated using the Child Behavior Checklist at ages 5–9 years (mean age 7 years, SD 1.1). Percentage of methylation for the NR3C1 gene promoter region was assessed from DNA extracted from maternal and child saliva using bisulfite pyrosequencing. Data analysis involved parametric and non-parametric correlations and multiple linear and logistic regression modeling. Results Logistic regression models using child NR3C1 methylation as the dependent variable and maternal NR3C1 methylation and PTSD group status as predictors, as well as the interaction indicated that all three of these significantly predicted child NR3C1 methylation. These findings remained significant when controlling for child age, sex and maternal child abuse history. Overall, maternal NR3C1 methylation when children were toddlers was negatively and significantly associated with child externalizing behavior severity at school age. Discussion We found that correlations between mothers and their children of NR3C1 methylation levels overall and at all individual CpG sites of interest were significant only in the IPV-PTSD group. The latter findings support that NR3C1 methylation in mothers positively and statistically significantly correlates with NR3C1 methylation in their children only in presence of IPV-PTSD in the mothers. This maternal epigenetic signature with respect to this glucocorticoid receptor is significantly associated with child behavior that may well pose a risk for intergenerational transmission of violence and related psychopathology.
Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins

A series of small-molecule fluoroquinolones were synthesized, characterized by HRMS and NMR spectroscopy, and screened for their antibacterial activity against MRSA, P. aeruginosa, and E. coli as model G+/G− pathogens. Compounds 2-e, 3-e, and 4-e were more potent than the reference drug balofloxacin against MRSA and P. aeruginosa (MIC values of 0.0195 and 0.039 μg/ml for 2-e, 0.039 and 0.078 μg/ml for each of 3-e and 4-e, respectively). Analysis of the time-dependent antibacterial effect of compound 2-e toward MRSA showed that in the early logarithmic growth phase, bactericidal effects occurred, while in the late logarithmic growth phase, bacterial inhibition occurred because of concentration effects and possibly the development of drug resistance. Compound 2-e exhibited low toxicity toward normal mammalian cell lines 3T3 and L-02 and tumor cell lines A549, H520, BEL-7402, and MCF-7. The compound was not hemolytic. Atomic force microscopy (AFM) revealed that compound 2-e could effectively destroy the membrane and wall of MRSA cells, resulting in the outflow of the cellular contents. Docking studies indicated the good binding profile of these compounds toward DNA gyrase and topoisomerase IV. ADMET’s prediction showed that most of the synthesized compounds followed Lipinski’s “rule of five” and possessed good drug-like properties. Our data suggested that compound 2-e exhibited potent anti-MRSA activity and is worthy of further investigation.
Time-resolved characterization of the innate immune response in the respiratory epithelium of human, porcine, and bovine during influenza virus infection

Viral cross-species transmission is recognized to be a major threat to both human and animal health, however detailed information on determinants underlying virus host tropism and susceptibility is missing. Influenza C and D viruses (ICV, IDV) are two respiratory viruses that share up to 50% genetic similarity, and both employ 9-O-acetylated sialic acids to enter a host cell. While ICV infections are mainly restricted to humans, IDV possesses a much broader host tropism and has shown to have a zoonotic potential. This suggests that additional virus–host interactions play an important role in the distinct host spectrum of ICV and IDV. In this study, we aimed to characterize the innate immune response of the respiratory epithelium of biologically relevant host species during influenza virus infection to identify possible determinants involved in viral cross-species transmission. To this end, we performed a detailed characterization of ICV and IDV infection in primary airway epithelial cell (AEC) cultures from human, porcine, and bovine origin. We monitored virus replication kinetics, cellular and host tropism, as well as the host transcriptional response over time at distinct ambient temperatures. We observed that both ICV and IDV predominantly infect ciliated cells, independently from host and temperature. Interestingly, temperature had a profound influence on ICV replication in both porcine and bovine AEC cultures, while IDV replicated efficiently irrespective of temperature and host. Detailed time-resolved transcriptome analysis revealed both species-specific and species uniform host responses and highlighted 34 innate immune-related genes with clear virus-specific and temperature-dependent profiles. These data provide the first comprehensive insights into important common and species-specific virus-host dynamics underlying the distinct host tropism of ICV and IDV, as well as possible determinants involved in viral cross-species transmission.
Rapid endothermal development of juvenile pacific bluefin tuna

An important trait of Pacific bluefin tuna (PBT) is their ability to maintain their body temperature above the ambient temperature, which allows them to occupy a wider ecological niche. However, the size at which this ability in nature develops is unclear. Therefore, this study aimed to clarify this point by monitoring the body temperature and the surrounding ambient temperature as the fish grew. PBT with fork lengths (FLs) ranging from 19.5 to 28.0 cm were implanted with archival electronic tags and released into the ocean. Data from 41 fish were obtained (recorded body and water temperatures, light level, and swimming depth (pressure) at 30-s intervals) and analyzed to elucidate the development of the ability of PBT to maintain a high body temperature. Body temperature of a PBT (< FL of ca. 40 cm) decreased in response to a vertical movement down to cooler depths, but higher body temperatures were maintained as the fish grew. The body temperature was then continuously maintained above ambient temperatures and fluctuated independently when fish attained more than 40 cm FL. Estimation of the whole-body heat-transfer coefficient and heat-production rate indicated that the latter decreased slowly with growth, while the former decreased by one order of magnitude when tuna reached 52 cm FL. Additionally, in the daytime, the whole-body heat-transfer coefficient was significantly higher than that at nighttime. Unlike other fishes including other Thunnus species, inhabiting tropical/subtropical waters, PBT rapidly acquire higher thermo-conservation ability when young, allowing capture of high-quality prey abundant in temperate waters to support high growth rates during early life.
Epidemiological and clinical characteristics of pertussis in children and their close contacts in households: A cross-sectional survey in Zhejiang Province, China

Background Despite the expanded immunization programs, the “re-emergence of pertussis” has become a global concern in recent years. At present, the prevalence of pertussis in China is seriously underestimated, and the role of close contact on the disease spreading in children remains unclear. Objectives Our study aimed to investigate pertussis’s epidemiological and clinical characteristics in children and their close contacts in households, as well as the antimicrobial resistance of Bordetella pertussis (B. pertussis) in Zhejiang Province, China. Methods We have collected the retrospective and prospective data of children who were suspected of pertussis and their close contacts in households from January 1, 2018, to December 31, 2020, in the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Nasopharyngeal swabs were collected and cultured for B. pertussis. Antibiotics susceptibility test was determined by using E-test methods. Clinical information was collected from the medical records systems. Results A total of 350 index patients and their 946 family members (close contacts in households) from 350 families were recruited. B. pertussis strains were isolated from 130 (37.1%) index patients and 116 (12.3%) close contacts. 37 index patients had negative culture results for B. pertussis while their close contacts were positive. A higher positive rate was found in female adults than that in male adults (16.3% vs. 5.1%, P < 0.01). The positive rate in index patients from multi-child families was significantly higher than that from one-child families (51.7% vs. 37.7%, P < 0.05). 53.3% of the pertussis patients were under 6 months of age. 98 (75.4%) isolates had MICs ≥ 256 mg/L to erythromycin, azithromycin, and clindamycin, and 127 (97.7%) had MICs < 0.016 mg/L to piperacillin. Conclusion Infants under 6 months of age are at high risk of pertussis, and close contacts in households are prone to cluster infection. Culture for B. pertussis both in children and their close contacts contributes to improving the diagnosis rate of pertussis in children. Isolates of B. pertussis in China are highly resistant to macrolides.
Prevalence and clinical characteristics of Crooke’s cell adenomas in 101 patients with T-PIT-positive pituitary adenomas: Case series and literature review

Purpose We aimed to perform a retrospective analysis of a rare subtype of corticotroph adenoma, Crooke’s cell adenoma, to better understand its clinical features. Methods We collected T-PIT-positive pituitary adenomas and screened Crooke’s cell adenomas from January 2020 to December 2021 in our center. Case reports of such tumors were also collected through a literature search. Clinical data such as biochemical tests, imaging examinations, and pathological data of the above cases were analyzed. Results A total of 101 T-PIT-positive patients were treated in our center in the last 2 years, and 4 were finally pathologically diagnosed with Crooke’s cell adenomas. All of these patients were male with elevated adrenocorticotropic hormone levels, and 50.0% presented with hypercortisolemia, Cushing’s syndrome, visual impairment, and headache. The tumor diameter was significantly larger in these 4 patients (37.0 mm) than in the other patients (26.0 mm), and their tumor invasive behavior was more pronounced. Cases reported in the literature were mainly female (72.8%), and the clinical presentation was also dominated by Cushing’s syndrome (65.1%) and hormonal dysfunction. Tumors were more common as macroadenomas (33.2 mm) and suprasellar growths (63.8%). The tumor recurrence rate was as high as 55.6%, with 6 cases progressing to pituitary carcinomas and 7.7% of tumor-related deaths. Our further integrated analysis of our center and reported cases revealed that gender, Cushing’s syndrome, visual dysfunction, hormonal disorders, and tumor growth characteristics were statistically different in different tumor categories. Conclusion Crooke’s cell adenoma is a tumor subtype with obvious clinical aggressive behavior, and an in-depth analysis of its clinical characteristics may assist in developing a comprehensive treatment plan.
The high degree of similarity in histopathological and clinical characteristics between radiogenic and sporadic papillary thyroid microcarcinomas in young patients

The potential overtreatment of patients with papillary thyroid microcarcinoma (MPTC) has been an important clinical problem in endocrine oncology over the past decade. At the same time, current clinical guidelines tend to consider prior radiation exposure as a contraindication to less extensive surgery, even for low-risk thyroid carcinomas, which primarily include microcarcinomas. This study aims to determine whether there are differences in the behavior of MPTC of two etiological forms (radiogenic and sporadic), including invasive properties, clinical data, and recurrence in patients aged up to 30 years. For this purpose, 136 radiogenic (from patients aged up to 18 years at the time of the Chornobyl accident) and 83 sporadic (from patients born after the Chornobyl accident) MPTCs were selected and compared using univariate and multivariate statistical methods in a whole group and in age and tumor size subgroups. No evidence of more aggressive clinical and histopathological behavior of radiogenic MPTCs as compared to sporadic tumors for basic structural, invasive characteristics, treatment options, and postoperative follow-up results was found. Moreover, radiogenic MPTCs were characterized by the lower frequencies of oncocytic changes (OR = 0.392, p = 0.004), nodal disease (OR = 0.509, p = 0.050), and more frequent complete remission (excellent response) after radioiodine therapy (OR = 9.174, p = 0.008). These results strongly suggest that internal irradiation does not affect tumor phenotype, does not associate with more pronounced invasive properties, and does not worsen prognosis in pediatric or young adult patients with MPTC, implying that radiation history may be not a pivotal factor for determining treatment strategy in such patients.
Two different domain architectures generate structural and functional diversity among bZIP genes in the Solanaceae family

The bZIP gene family is one of the largest transcription factor families and has important roles in plant growth, development, and stress responses. However, bZIP genes in the Solanaceae family have not been extensively investigated. Here, we conducted genome-wide re-annotation in nine Solanaceae species and Arabidopsis thaliana. We annotated 935 bZIP genes, including 107 (11%) that were newly identified. Structural analyses of bZIP genes in the Solanaceae family revealed that the bZIP domain displayed two types of architectures depending on the presence of an additional domain, suggesting that these architectures generate diversified structures and functions. Motif analyses indicated that the two types of bZIP genes had distinct sequences adjacent to the bZIP domain. Phylogenetic analyses suggested that the two types of bZIP genes distinctly evolved and ultimately adapted in different lineages. Transcriptome analyses in pepper (Capsicum annuum) and tomato (Solanum lycopersicum) revealed putative functional diversity between the two types of bZIP genes in response to various abiotic stresses. This study extensively updated bZIP gene family annotations and provided novel evolutionary and functional evidence for the role of bZIP genes in Solanaceae plants. Our findings provide evolutionary and functional characteristics of bZIP genes for a better understanding of their roles in Solanaceae plants.
Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

In human patients and animal models of ulcerative colitis (UC), upregulation of the mitochondrial translocator protein (TSPO) in the colon is consistent with inflammation. Although the molecular function for TSPO remains unclear, it has been investigated as a therapeutic target for ameliorating UC pathology. In this study, we examined the susceptibility of Tspo gene-deleted (Tspo −/− ) mice to insults as provided by the dextran sodium sulfate (DSS)-induced acute UC model. Our results show that UC clinical signs and pathology were severely exacerbated in Tspo −/− mice compared to control Tspo fl/fl cohorts. Histopathology showed extensive inflammation and epithelial loss in Tspo −/− mice that caused an aggravated disease. Colonic gene expression in UC uncovered an etiology linked to precipitous loss of epithelial integrity and disproportionate mast cell activation assessed by tryptase levels in Tspo −/− colons. Evaluation of baseline homeostatic shifts in Tspo −/− colons revealed gene expression changes noted in elevated epithelial Cdx2, mast cell Cd36 and Mcp6, with general indicators of lower proliferation capacity and elevated mitochondrial fatty acid oxidation. These findings demonstrate that intact physiological TSPO function serves to limit inflammation in acute UC, and provide a systemic basis for investigating TSPO-targeting mechanistic therapeutics.