Discriminating bronchiolar adenoma from peripheral lung cancer by thin-section computed tomography (CT): a 2-center study.

Background: Bronchiolar adenoma (BA) is frequently misdiagnosed as peripheral lung cancer (PLC) because it resembles PLC. Computed tomography (CT) examination is an effective tool for detecting and diagnosing lung diseases. To date, there has been no comprehensive study on the differential diagnosis of BAs and PLCs using thin-section computed tomography (TSCT) based on a large sample, and the efficiency of CT in diagnosing BAs has not been verified. The goal of this study was to distinguish BA from PLC by summarizing their clinical and TSCT characteristics. Methods: A retrospective cross-sectional study on 71 cases with BAs and 218 matched controls with PLCs (from March 2020 to May 2023) within 2 centers (The First Affiliated Hospital of Chongqing Medical University and the Second Affiliated Hospital of Army Medical University) was conducted to investigate their clinical and radiological differences. The clinical characteristics and TSCT features of BAs and PLCs were summarized and compared. A multivariate logistic regression analysis was performed to reveal the key predictors of BAs. Results: The BAs and PLCs exhibited significant differences in TSCT features. Multivariate analysis revealed that the lesion being located in basal segments [odds ratio (OR), 17.835; 95% confidence interval (CI): 6.977-45.588; P<0.001], irregular shape (OR, 4.765; 95% CI: 1.877-12.099; P=0.001), negative of spiculation sign (OR, 7.436; 95% CI: 2.063-26.809; P=0.002), central vessel sign with pulmonary artery (OR, 3.576; 95% CI: 1.557-8.211; P=0.003), peripheral vessel sign with pulmonary vein (OR, 12.444; 95% CI: 4.934-31.383; P<0.001), and distance from lesion edge to pleura (D-ETP) ≤5 mm (OR, 5.535; 95% CI: 2.346-13.057; P<0.001) were independent predictors of BAs, and the area under the curve (AUC) of this model was 0.935; 95% CI: 0.901-0.960 (sensitivity: 88.0%, specificity: 86.03%, P<0.001). Conclusions: Peripheral pulmonary nodules locating in the basal segment of lower lobe with irregular shape, central vessel sign with pulmonary artery, peripheral vessel sign with pulmonary vein and D-ETP ≤5 mm, but without spiculation sign, should be highly suspected of BAs.

Development and characterization of a recombinant Senecavirus A expressing enhanced green fluorescent protein.

Introduction: Senecavirus A (SVA), belonging to the genus Senecavirus in the family Picornaviridae, is an emerging pathogen causing vesicular disease in pigs. The main clinical manifestations of SVA infection include high mortality in neonatal piglets, skin ulceration, and vesicular lesions. So far, there is no commercially available vaccines or drugs against SVA. Construction of SVA infectious clones carrying reporter genes will help understand the characteristics of SVA and promote vaccine development. Methods: In this study, we established a reverse genetics system for a local SVA isolate and used it to rescue a recombinant SVA, rSVA-eGFP, expressing the enhanced green fluorescent protein (eGFP) by inserting eGFP, GSG linker and the P2A sequence between 2A and 2B genes. Results: We found that rSVA-eGFP exhibited a high replication efficiency comparable to the parental virus, was able to express the eGFP reporter efficiently and stable in maintaining the reporter gene up to six rounds of serial passages in BHK-21 cells. In mice, rSVA-eGFP also showed similar replication kinetics and pathogenicity to the parental virus, both causing mild lung lesions. In addition, a high-throughput viral neutralization assay was developed using eGFP as a surrogate readout in a fluorescence-based direct titration (FBT) assay based on rSVA-eGFP, facilitating rapid and accurate determination of the neutralizing antibody (nAb) titers. Discussion: The successful establishment of an SVA reverse genetics system and the rescue of rSVA-eGFP would create a powerful tool for future studies of SVA replication mechanisms and pathogenicity as well as for antiviral development.

Performance and mechanism of diclofenac adsorption onto 3D poly(m-phenylenediamine)-grafted melamine foam via batch experiment and theoretical studies.

Seeking highly efficient adsorbents for pharmaceuticals and personal care products (PPCPs) removal has been a worldwide continuing endeavor. In this study, a new 3D composite material was synthesized by covalently anchoring Poly(m-Phenylenediamine) onto 3D polyvinyl alcohol modified foam framework (PmPD-MF-PVA). PmPD-MF-PVA was characterized and evaluated for its efficacy in removing diclofenac (DCF), a commonly detected PPCPs in both wastewater and surface water. Results showed that the adsorption capacity of PmPD-MF-PVA toward DCF was 1.5 times higher than that of PmPD-MF. The addition of PVA increased deposition area of PmPD, and promoted PmPD loading on the foam surface. Batch adsorption experiments exhibited that the adsorption of DCF was fitted well with Langmuir isotherm and pseudo-second-order kinetic models. The maximum adsorption capacity of PmPD-MF-PVA was 115 mg/g. Meanwhile, PmPD-MF-PVA exhibited better separation ability than the hard-to-separate PmPD. Characterization analysis and density functional theory (DFT) calculation elucidated the main mechanisms of DCF adsorption on PmPD-MF-PVA. Hydrogen bonding and π-π interactions were main drivers for DCF adsorption, followed by electrostatic attraction and hydrophobic forces. This study provides an effective strategy to overcome the drawbacks of PmPD, such as recycling difficulty and agglomeration problems, offering valuable insights for the design of polymers-based adsorbents.

Comparison of sublethal effects of 3 acaricides on life table parameters of Tetranychus urticae Koch (Acari: Tetranychidae) and Polyphagotarsonemus latus Banks (Acari: Tarsonemidae).

To assess the effects of sublethal concentrations of 3 acaricides-Bifenazate, Etoxazole, and Azocyclotin-on the development and reproduction of Tetranychus urticae Koch (Acari: Tetranychidae) and Polyphagotarsonemus latus Banks. Our results indicated that the LC20 values of Bifenazate, Etoxazole, and Azocyclotin against T. urticae are 3.196, 25.249, and 32.387 mg/L, and against P. latus to be 18.058, 4.641, and 13.755 mg/L, respectively. Sublethal concentrations of these acaricides significantly impacted the development time, lifespan, and fecundity of both mite species. Among the acaricides, Azocyclotin significantly extended the immature developmental period of T. urticae and P. latus. All acaricides reduced the lifespan and fecundity of both species, with Etoxazole having the most substantial impact on the daily fecundity and reproductive of T. urticae. The intrinsic rates of natural increase (rm) for T. urticae exposed to Bifenazate, Etoxazole, and Azocyclotin were 0.17, -0.04, and 0.20, respectively. For P. latus, the rm values were 0.27, 0.23, and 0.25, respectively. These results suggest that under the exposure of sublethal acaricides, P. latus gained a competitive advantage in population competition. These findings underscore the importance of understanding the differential impacts of acaricides on various mite species to develop effective pest management strategies.

Small GTP-binding protein GDP dissociation stimulator influences cisplatin-induced acute kidney injury via PERK-dependent ER stress.

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK in vivo and in vitro. Furthermore, we confirmed that smgGDS deficiency aggravated apoptosis and ER stress in vivo and in vitro. And the ER stress inhibitor 4-Phenylbutyric acid and the inhibition of PERK phosphorylation mitigated smgGDS deficiency-induced ER stress related apoptosis following cisplatin treatment, while the eIF2α phosphorylation inhibitor could not reverse the smgGDS deficiency accelerated cell death. Furthermore, the over-expression of smgGDS could reverse the ER stress and apoptosis caused by CDDP. Overall, smgGDS regulated PERK-dependent ER stress and apoptosis, thereby influencing renal damage. This study identified a target for diagnosing and treating cisplatin-induced acute kidney injury.

Artificial intelligence-measured nodule mass for determining the invasiveness of neoplastic ground glass nodules.

Background: The nodule mass is an important indicator for evaluating the invasiveness of neoplastic ground-glass nodules (GGNs); however, the efficacy of nodule mass acquired by artificial intelligence (AI) has not been validated. This study thus aimed to determine the efficacy of nodule mass measured by AI in predicting the invasiveness of neoplastic GGNs. Methods: From May 2019 to September 2023, a retrospective study was conducted on 755 consecutive patients comprising 788 pathologically confirmed neoplastic GGNs, among which 259 were adenocarcinoma in situ (AIS), 282 minimally invasive adenocarcinoma (MIA), and 247 invasive adenocarcinoma (IAC). Nodule mass was quantified using AI software, and other computed tomography (CT) features were concurrently evaluated. Clinical data and CT features were compared using the Kruskal-Wallis test or Pearson chi-square test. The predictive efficacy of mass and CT features for evaluating invasive lesions (ILs) (MIAs and IACs) and IACs was analyzed and compared via receiver operating characteristic (ROC) analysis and the Delong test. Results: ROC curve analysis revealed that the optimal cutoff value of mass for distinguishing ILs and AISs was 225.25 mg [area under the curve (AUC) 0.821; 95% confidence interval 0.792-0.847; sensitivity 64.27%; specificity 89.19%; P<0.001], and for differentiating IACs from AISs and MIAs, it was 390.4 mg (AUC 0.883; 95% confidence interval 0.858-0.904; sensitivity 80.57%; specificity 86.32%; P<0.001). The efficacy of nodule mass in distinguishing ILs and AISs was comparable to that of size (P=0.2162) and significantly superior to other CT features (each P value <0.001). Additionally, the ability of nodule mass to differentiate IACs from AISs and MIAs was significantly better than that of CT features (each P value <0.001). Conclusions: AI-based nodule mass analysis is an effective indicator for determining the invasiveness of neoplastic GGNs.

Altitude-related features and prognosis in patients with reversible splenial lesion syndrome.

INTRODUCTION: RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure. METHODS: Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023. RESULTS: Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate. CONCLUSIONS: Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.

The role of forkhead box M1-methionine adenosyltransferase 2 A/2B axis in liver inflammation and fibrosis.

Methionine adenosyltransferase 2 A (MAT2A) and MAT2B are essential for hepatic stellate cells (HSCs) activation. Forkhead box M1 (FOXM1) transgenic mice develop liver inflammation and fibrosis. Here we examine if they crosstalk in male mice. We found FOXM1/MAT2A/2B are upregulated after bile duct ligation (BDL) and carbon tetrachloride (CCl4) treatment in hepatocytes, HSCs and Kupffer cells (KCs). FDI-6, a FOXM1 inhibitor, attenuates the development and reverses the progression of CCl4-induced fibrosis while lowering the expression of FOXM1/MAT2A/2B, which exert reciprocal positive regulation on each other transcriptionally. Knocking down any of them lowers HSCs and KCs activation. Deletion of FOXM1 in hepatocytes, HSCs, and KCs protects from BDL-mediated inflammation and fibrosis comparably. Interestingly, HSCs from Foxm1Hep-/-, hepatocytes from Foxm1HSC-/-, and HSCs and hepatocytes from Foxm1KC-/- have lower FOXM1/MAT2A/2B after BDL. This may be partly due to transfer of extracellular vesicles between different cell types. Altogether, FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.

FN1, a reliable prognostic biomarker for thyroid cancer, is associated with tumor immunity and an unfavorable prognosis.

Thyroid cancer (THCA) is a malignant tumor that affects the endocrine system. At present, an effective treatment for THCA remains elusive, particularly for medullary carcinoma and undifferentiated carcinoma, due to the lack of suitable medications and prognostic markers. Patient RNA-sequencing and clinical data were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Protein-protein interaction analyses were performed for differentially expressed genes related to THCA. Moreover, the associations between fibronectin 1 (FN1), clinical data, immune checkpoint genes and immune cell infiltration was assessed. The potential functional role of the FN1 gene was evaluated through gene set enrichment analysis. Immunohistochemistry was used to assess FN1 expression in 103 cases of THCA, comprising 32 with papillary carcinoma, 30 with follicular carcinoma, 35 with medullary carcinoma and 6 with undifferentiated carcinoma. Finally, 11 co-expression modules were constructed and the expression of five identified hub genes (FN1, mucin-1, keratin 19, intracellular adhesion molecule 1 and neural cell adhesion molecule) were evaluated. The results demonstrated that higher FN1 gene expression levels were strongly associated with a higher pathologic stage and tumor stage, and were significantly associated with immune cell infiltration in THCA. Significant increases in FN1 protein expression levels were noted among patients diagnosed with four types of THCA, comprising papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Patients diagnosed with medullary carcinoma and undifferentiated carcinoma, and with low FN1 expression levels, exhibited a significant survival advantage compared with those with high FN1 expression levels. In conclusion, the present study identified five hub genes involved in the onset and progression of THCA. Furthermore, FN1 could serve as a candidate biomarker and a therapeutic target for THCA and may be a key gene mediating THCA immune infiltration.

Gene therapy in Aß-induced cell and mouse models of Alzheimer's disease through compensating defective mitochondrial complex I function.

BACKGROUND: Alzheimer's disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. METHODS: The differentiated human neural cells were induced by Aß1-42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aß1-42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. RESULTS: The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. CONCLUSIONS: Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aß-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.

Treadmill running on neuropathic pain: via modulation of neuroinflammation.

Neuropathic pain is a type of chronic pain caused by an injury or somatosensory nervous system disease. Drugs and exercise could effectively relieve neuropathic pain, but no treatment can completely stop neuropathic pain. The integration of exercise into neuropathic pain management has attracted considerable interest in recent years, and treadmill training is the most used among exercise therapies. Neuropathic pain can be effectively treated if its mechanism is clarified. In recent years, the association between neuroinflammation and neuropathic pain has been explored. Neuroinflammation can trigger proinflammatory cytokines, activate microglia, inhibit descending pain modulatory systems, and promote the overexpression of brain-derived neurotrophic factor, which lead to the generation of neuropathic pain and hypersensitivity. Treadmill exercise can alleviate neuropathic pain mainly by regulating neuroinflammation, including inhibiting the activity of pro-inflammatory factors and over activation of microglia in the dorsal horn, regulating the expression of mu opioid receptor expression in the rostral ventromedial medulla and levels of γ-aminobutyric acid to activate the descending pain modulatory system and the overexpression of brain-derived neurotrophic factor. This article reviews and summarizes research on the effect of treadmill exercise on neuropathic pain and its role in the regulation of neuroinflammation to explore its benefits for neuropathic pain treatment.

Optional Revascularization Strategies for Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease.

Percutaneous coronary intervention is the main strategy of revascularization and has been shown to improve outcomes in some patients with ST-segment elevation myocardial infarction (STEMI). However, multivessel disease (MVD), a common condition in these patients, is associated with worse clinical outcomes compared to single-vessel disease. Despite intervention being a standard treatment for coronary artery disease, optimal strategies and timings for patients with STEMI and MVD remain unclear. Numerous studies and meta-analyses have investigated this topic; however, many current conclusions are based on observational studies. Furthermore, clinical guidelines regarding the management of patients with STEMI and MVD contain conflicting recommendations. Therefore, we aimed to compile relevant studies and newly available evidence-based medicines to explore the most effective approach.

SP1 regulates BMSC osteogenic differentiation through the miR-133a-3p/MAPK3 axis : SP1 regulates osteogenic differentiation of BMSCs.

BACKGROUND: The progression of osteoporosis (OP) can dramatically increase the risk of fractures, which seriously disturb the life of elderly individuals. Specific protein 1 (SP1) is involved in OP progression. However, the mechanism by which SP1 regulates OP progression remains unclear. OBJECTIVE: This study investigated the mechanism underlying the function of SP1 in OP. METHODS: SAMP6 mice were used to establish an in vivo model of age-dependent OP, and BALB/c mice were used as controls. BMSCs were extracted from two subtypes of mice. Hematoxylin and eosin staining were performed to mark the intramedullary trabecular bone structure to evaluate histological changes. ChIP assay was used to assess the targeted regulation between SP1 and miR-133a-3p. The binding sites between MAPK3 and miR-133a-3p were verified using a dual-luciferase reporter assay. The mRNA levels of miR-133a-3p and MAPK3 were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The protein expression of SP1, MAPK3, Colla1, OCN, and Runx2 was examined using Western blotting. Alkaline phosphatase (ALP) kit and Alizarin Red S staining were used to investigate ALP activity and mineralized nodules, respectively. RESULTS: The levels of SP1 and miR-133a-3p were upregulated, whereas the expression of MAPK3 was downregulated in BMSCs from SAMP6 mice, and miR-133a-3p inhibitor accelerated osteogenic differentiation in BMSCs. SP1 directly targeted miR-133a-3p, and MAPK3 was the downstream mRNA of miR-133a-3p. Mechanically, SP1 accelerated osteogenic differentiation in BMSCs via transcriptional mediation of the miR-133a-3p/MAPK3 axis. CONCLUSION: SP1 regulates osteogenic differentiation by mediating the miR-133a-3p/MAPK3 axis, which would shed new light on strategies for treating senile OP.

Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis.

OBJECTIVE: This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype-phenotype correlations in Chinese patients with hereditary spherocytosis (HS). METHODS: Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years). RESULTS: A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences. CONCLUSION: This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.

Dietary supplementation of Sida rhombifolia enhances the plasma antioxidation and modulates gut microbiota in Anyi tile-like grey chickens.

Sida rhombifolia (S. rhombifolia) is a widely used herbal plant for humans because of its antioxidant and antibacterial effects, but its potential use as a feed additive for livestock has not been investigated. Twenty 350 days-old Anyi tile-like grey chickens were randomly divided into a control group (fed basal diet) and a treatment group (fed basal diet + 3% of S. rhombifolia), and these chickens were feed for 31 days. Dietary S. rhombifolia remarkably enhanced plasma antioxidants, including the significantly increased total antioxidant capability (p < 0.01), catalase (p = 0.04), and superoxide dismutase (p < 0.01) in the treatment group. Furthermore, dietary S. rhombifolia also modulated chicken cecal microbiota, including an increased microbial diversity (Shannon, p = 0.03; Chao1, p = 0.03) in the treatment group. Regarding taxonomic analysis, 34 microbial taxa showed significant differences between the two groups. Meanwhile, the dominant phylum Actinobacteriota (p = 0.04), and dominant genera Desulfovibrio (p = 0.04) and Olsenella (p = 0.02) were significantly increased after treatment, whereas the pathogenic genus Escherichia-Shigella (p = 0.04) was significantly decreased after feeding S. rhombifolia. The results indicating that S. rhombifolia has potential for use as a natural plant feed additive for chickens.

Identification and Evaluation of Reversible Covalent Binders to Cys55 of Bfl-1 from a DNA-Encoded Chemical Library Screen.

Bfl-1 is overexpressed in both hematological and solid tumors; therefore, inhibitors of Bfl-1 are highly desirable. A DNA-encoded chemical library (DEL) screen against Bfl-1 identified the first known reversible covalent small-molecule ligand for Bfl-1. The binding was validated through biophysical and biochemical techniques, which confirmed the reversible covalent mechanism of action and pointed to binding through Cys55. This represented the first identification of a cyano-acrylamide reversible covalent compound from a DEL screen and highlights further opportunities for covalent drug discovery through DEL screening. A 10-fold improvement in potency was achieved through a systematic SAR exploration of the hit. The more potent analogue compound 13 was successfully cocrystallized in Bfl-1, revealing the binding mode and providing further evidence of a covalent interaction with Cys55.

Prevalence, Genotype Diversity, and Distinct Pathogenicity of 205 Gammacoronavirus Infectious Bronchitis Virus Isolates in China during 2019-2023.

Gammacoronavirus infectious bronchitis virus (IBV) causes a highly contagious disease in chickens and seriously endangers the poultry industry. The emergence and co-circulation of diverse IBV serotypes and genotypes with distinct pathogenicity worldwide pose a serious challenge to the development of effective intervention measures. In this study, we report the epidemic trends of IBV in China from 2019 to 2023 and a comparative analysis on the antigenic characteristics and pathogenicity of isolates among major prevalent lineages. Phylogenetic and recombination analyses based on the nucleotide sequences of the spike (S) 1 gene clustered a total of 205 isolates into twelve distinct lineages, with GI-19 as a predominant lineage (61.77 ± 4.56%) exhibiting an overall increasing trend over the past five years, and demonstrated that a majority of the variants were derived from gene recombination events. Further characterization of the growth and pathogenic properties of six representative isolates from different lineages classified four out of the six isolates as nephropathogenic types with mortality rates in one-day-old SPF chickens varying from 20-60%, one as a respiratory type with weak virulence, and one as a naturally occurring avirulent strain. Taken together, our findings illuminate the epidemic trends, prevalence, recombination, and pathogenicity of current IBV strains in China, providing key information for further strengthening the surveillance and pathogenicity studies of IBV.

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. METHODS: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. RESULTS: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (ß, 95%CI: -10.74, 1.13) to -9.00 (ß, 95%CI: -15.03, -2.99) and then to -6.77 (ß, 95%CI: -12.83, -0.71, p for trend = 0.0212) µmol/L when increasing the quartile of vitamin D3. CONCLUSIONS: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.

The mental health and traumatic experiences of mothers of children with 22q11DS.

Background: 22q11 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome with broad phenotypic variability, leading to significant morbidity and some mortality. The varied health problems associated with 22q11DS and the evolving phenotype (both medical and developmental/behavioural) across the lifespan can strongly impact the mental health of patients as well as their caregivers. Like caregivers of children with other chronic diseases, caregivers of children with 22q11DS may experience an increased risk of traumatisation and mental health symptoms.Objective: The study's primary objective was to assess the frequency of traumatic experiences and mental health symptoms among mothers of children with 22q11DS. The secondary objective was to compare their traumatic experiences to those of mothers of children with other neurodevelopmental disorders (NDDs).Method: A total of 71 mothers of children diagnosed with 22q11DS completed an online survey about their mental health symptoms and traumatic experiences. Descriptive statistics were used to summarise the prevalence of their mental health symptoms and traumatic experiences. Logistic regression models were run to compare the traumatic experiences of mothers of children with 22q11DS to those of 335 mothers of children with other neurodevelopmental disorders (NDDs).Results: Many mothers of children with 22q11DS experienced clinically significant mental health symptoms, including depression (39%), anxiety (25%), and post-traumatic stress disorder (PTSD) symptoms (30%). The types of traumatic events experienced by mothers of children with 22q11DS differed from those of mothers of children with other NDDs as they were more likely to observe their child undergoing a medical procedure, a life-threatening surgery, or have been with their child in the intensive care unit.Conclusion: 22q11DS caregivers are likely to require mental health support and trauma-informed care, tailored to the specific needs of this population as they experience different kinds of traumatic events compared to caregivers of children with other NDDS.

Mothers of children with 22q11DS experience clinically significant levels of depression, anxiety, and PTSD.Mothers of children with 22q11DS experience many and diverse trauma particularly related to medical interventions of their child.The types of traumatic events experienced by mothers of children with 22q11DS are different from those of the mothers of children with other neurodevelopmental disorders.

Anlotinib induces neuronal-like differentiation of neuroblastoma by downregulating CRMP5.

The therapeutic effect of anlotinib on neuroblastoma is still not fully understood. This study aims to explore the differentiation therapeutic effects of anlotinib on neuroblastoma and its potential association with the neural development regulatory protein collapsin response mediator protein 5 (CRMP5), both in vivo and in vitro. A patient-derived xenograft (PDX) model was established to observe the therapeutic effect of anlotinib. Neuroblastoma cell lines SK-N-SH and SK-N-AS were cultured to observe the morphological impact of anlotinib. Transwell assay was used to evaluate the cell invasion, and Western blot analysis and immunohistochemistry were employed to detect the expressions of neuronal differentiation-related proteins. Results indicate that anlotinib effectively inhibited tumor growth in the PDX model, modulated the expressions of neuronal differentiation markers. In vitro, anlotinib treatment induced neurite outgrowth in neuroblastoma cells and inhibited their invasive ability, reflecting a change in neuronal marker expression patterns consistent with the PDX model. Similarly, in the SK-N-AS mouse xenograft model, anlotinib demonstrated comparable tumor-suppressing effects and promoted neuronal-like differentiation. Additionally, anlotinib significantly downregulated CRMP5 expression in neuroblastoma both in vivo and in vitro. Overexpression of CRMP5 significantly reversed the differentiation therapy effect of anlotinib, exacerbating the aggressiveness and reducing the differentiation level of neuroblastoma. These findings highlight the potential of anlotinib as an anti-neuroblastoma agent. It may suppress tumor proliferation and invasion by promoting the differentiation of tumor cells towards a neuronal-like state, and this differentiation therapy effect involves the inhibition of CRMP5 signaling.