Immunomodulation in allergic rhinitis: Insights from Th2 cells and NLRP3/IL-18 pathway.

Allergic rhinitis (AR) is characterized by nasal symptoms such as rubbing and sneezing, often triggered by allergen exposure. The purpose of this study is to dissect the roles of NLRP3-mediated immune modulation and macrophage pyroptosis in modulating T cell differentiation within the context of ovalbumin (OVA)-induced AR in mice. OVA-induced AR was established in mice, evaluating nasal symptoms, macrophage infiltration, cytokine levels, and T cell differentiation. Manipulations using NLRP3-/-, ASC-/- mice, clodronate liposome treatment, and NLRP3 inhibitor MCC950 were performed to assess their impact on AR symptoms and immune responses. Following OVA stimulation, increased nasal symptoms were observed in the OVA group along with augmented GATA3 expression and elevated IL-4 and IL-1b levels, indicative of Th2 polarization and cellular pyroptosis involvement. NLRP3-/- and ASC-/- mice exhibited reduced CD3+ T cells post OVA induction, implicating cellular pyroptosis in AR. Macrophage depletion led to decreased IgE levels, highlighting their involvement in allergic responses. Further investigations revealed enhanced macrophage pyroptosis, influencing Th1/Th2 differentiation in AR models. IL-18 released through NLRP3-mediated pyroptosis induced Th2 differentiation, distinct from IL-1b. Additionally, MCC950 effectively mitigated AR symptoms by modulating Th2 responses and reducing macrophage infiltration. This comprehensive study unravels the pivotal role of NLRP3-mediated immune modulation and macrophage pyroptosis in Th1/Th2 balance regulation in OVA-induced AR. Targeting NLRP3 pathways with MCC950 emerged as a promising strategy to alleviate AR symptoms, providing insights for potential therapeutic interventions in AR management.

EGFR and ERBB2 Exon 20 Insertion Mutations in Chinese Non-small Cell Lung Cancer Patients: Pathological and Molecular Characterization, and First-Line Systemic Treatment Evaluation.

BACKGROUND: Data from studies looking at both EGFR and ERBB2 exon 20 insertion mutations (-20ins) in the same cohort of patients with non-small cell lung cancer (NSCLC) are limited. OBJECTIVE: The purpose of this study was to analyze EGFR/ERBB2-20ins in all-stage NSCLC patients to reveal their histological and molecular features, and to retrospectively evaluate the results of first-line real-world systemic treatments in patients with advanced-stage disease. PATIENTS AND METHODS: We collected 13,920 formalin-fixed paraffin-embedded NSCLC specimens. Clinicopathological features were recorded and DNA-based next-generation sequencing was performed. First-line systemic treatment data were obtained via chart review. RESULTS: In total, 414 (2.97%) EGFR-20ins cases and 666 (4.78%) ERBB2-20ins cases were identified. Both were more common in women, non-smokers, and patients with adenocarcinoma. The incidence of EGFR/ERBB2-20ins in adenocarcinoma is inversely proportional to the degree of invasion; 77 and 26 variants were detected in EGFR-20ins and ERBB2-20ins cases, respectively. The most common concurrently mutated genes were TP53 and RB1. In invasive adenocarcinoma, lepidic components were more common in EGFR/ERBB2-20ins-alone cases than in those with other concurrent mutated genes. In EGFR-/ERBB2-20ins patients, there was no significant difference in progression-free survival (PFS) or treatment response to first-line systemic treatments in this study. There was no significant difference in PFS or treatment response among patients with different EGFR/ERBB2-20ins variants and those with or without concurrent mutated genes. CONCLUSIONS: EGFR/ERBB2-20ins is more common in early lung adenocarcinoma. EGFR-20ins had more variants. In both cohorts, the results for first-line systemic treatments showed no significant difference.

Analysis of swallowing and voice-related quality of life in patients after supracricoid partial laryngectomy.

OBJECTIVE: This study evaluated the swallowing and voice function of laryngeal cancer patients after Supracricoid Partial Laryngectomy(SCPL), and its influence on quality of life to provide a reference for the selection of surgical methods for laryngeal cancer patients. METHODS: Twenty-one patients who received SCPL between April 2015 and November 2021 were included. Each patient's swallowing function and quality of life were assessed through fiberoptic endoscopic examination of swallowing (FEES) and the M.D. Anderson Dysphagia Inventory (MDADI). Fundamental, jitter, shimmer, maximum phonation time (MPT), and voice handicap index-10 (VHI-10) were performed to assess voice function and voice-related quality of life. RESULTS: The results of the FEES of the 21 patients were as follows: the rates of pharyngeal residue after swallowing solid, semiliquid, and liquid food were 0%, 28.57%, and 38.09%, respectively; the rates of laryngeal infiltration after swallowing solid, semiliquid, and liquid food were 0%, 28.57%, and 4.76%, respectively; and aspiration did not occur in any of the patients. In the evaluation of swallowing quality of life, the mean total MDADI score was 92.6 ± 6.32. The voice function evaluation showed that the mean F0, jitter, shimmer, and MPT values were 156.01 ± 120.87 (HZ), 11.57 ± 6.21 (%), 35.37 ± 14.16 (%) and 7.85 ± 6.08 (s), respectively. The mean total VHI-10 score was 7.14 ± 4.84. CONCLUSION: SCPL provides patients with satisfactory swallowing and voice function. The patients in this study were satisfied with their quality of life in terms of swallowing and voice. SCPL can be used as a surgical method to preserve laryngeal function in patients with laryngeal cancer.

Aporphine and amide alkaloids from Illigera parviflora.

Three undescribed alkaloids (+)-9-hydroxy-N-acetylnordicentrine (1), illigeparvinine (2), and deca-(2E,4Z)-2,4-dienoic acid 4-hydroxy-2-phenethyl amide (3), along with 19 known analogues (4-22), were isolated from the ethnic medicinal plant Illigera parviflora. Their structures were established using NMR, MS, and other spectroscopic analyses as well as X-ray diffraction. Moderate inhibition of human gastric carcinoma (MGC-803) and breast adenocarcinoma (T-47D) cell lines proliferation was observed for actinodaphnine (4) with IC50 values of 28.74 and 11.65 µM, respectively. These findings contribute new anticancer potential compounds and expand the chemical diversity known from the valuable traditional medicinal plant I. parviflora.

M-type pyruvate kinase 2 (PKM2) tetramerization alleviates the progression of right ventricle failure by regulating oxidative stress and mitochondrial dynamics.

BACKGROUND: Right ventricle failure (RVF) is a progressive heart disease that has yet to be fully understood at the molecular level. Elevated M-type pyruvate kinase 2 (PKM2) tetramerization alleviates heart failure, but detailed molecular mechanisms remain unclear. OBJECTIVE: We observed changes in PKM2 tetramerization levels during the progression of right heart failure and in vitro cardiomyocyte hypertrophy and explored the causal relationship between altered PKM2 tetramerization and the imbalance of redox homeostasis in cardiomyocytes, as well as its underlying mechanisms. Ultimately, our goal was to propose rational intervention strategies for the treatment of RVF. METHOD: We established RVF in Sprague Dawley (SD) rats by intraperitoneal injection of monocrotaline (MCT). The pulmonary artery pressure and right heart function of rats were assessed using transthoracic echocardiography combined with right heart catheterization. TEPP-46 was used both in vivo and in vitro to promote PKM2 tetramerization. RESULTS: We observed that oxidative stress and mitochondrial disorganization were associated with increased apoptosis in the right ventricular tissue of RVF rats. Quantitative proteomics revealed that PKM2 was upregulated during RVF and negatively correlated with the cardiac function. Facilitating PKM2 tetramerization promoted mitochondrial network formation and alleviated oxidative stress and apoptosis during cardiomyocyte hypertrophy. Moreover, enhancing PKM2 tetramer formation improved cardiac mitochondrial morphology, mitigated oxidative stress and alleviated heart failure. CONCLUSION: Disruption of PKM2 tetramerization contributed to RVF by inducing mitochondrial fragmentation, accumulating ROS, and finally promoted the progression of cardiomyocyte apoptosis. Facilitating PKM2 tetramerization holds potential as a promising therapeutic approach for RVF.

[An analysis of the wall width before and after root canal therapy in mandibular second molars with C-shaped canals].

PURPOSE: To measure the wall width in mandibular second molars with C-shaped canals before and after root canal therapy using cone-beam CT(CBCT). METHODS: A total of 55 mandibular second molars from 38 patients which met the criteria for inclusion at Nanjing Stomatological Hospital, Affiliated Stomatological Hospital of Medical School of Nanjing University from January 2020 to July 2021 were analyzed．From this sample, ten teeth had been treated, while another 45 of them not. CT images of the teeth were reestablished by Mimics software 20.0. Then we made a section every 1mm perpendicular to the long axis of the teeth from apex to pulp floor. The first slice from apex to pulp chamber was named the slice 1. Along the slice 1 to crown 1 mm was called slice 1, and so forth. The wall thickness at different locations of all the slices was measured. The data was entered into SPSS 20.0 software package for analysis. RESULTS: Regardless of whether the teeth were treated or not, both the mesial and distal canal walls' average width were thicker than 1mm in all slices. At the same time, the mesial and distal canal walls' width were thicker than the width of buccal and lingual canal walls in all the slices from C-shaped root canal, except slices which were near pulp chamber(P＜0.05). As for the C-shaped root canals without root canal therapy, the width of lingual wall in the slice 1 to 4, as well as apex third root, was thinner than 1 mm. The width of buccal canal wall was thicker than the width of lingual canal wall in all slices except slice 11 and 12. As for the C-shaped root canals with root canal therapy, the width of buccal canal wall in slice 1 to 5, equivalent of apex half root, and the width of lingual wall in the slice 1 to 7, amount to apex two-thirds of root, was thinner than 1 mm. The width of buccal canal wall was thicker than the width of lingual wall in all slices except slice 1 and 9. There was no significant difference between the distal canal walls' width of C-shaped canals with and without root canal therapy(P＞0.05) . There was significant difference between the buccal canal walls' width of C-shaped canals with and without root canal therapy, as same as the mesial canal walls' width and the width of lingual canal wall (P＜0.05). CONCLUSIONS: The lingual canal walls' width in apex third root of C-shaped root canal were thin before canal preparation. The buccal walls' width in apex half root and the lingual canal walls' in apex two-thirds of root of C-shaped root canal were thin after canal preparation.

Clinical observation of Gofried positive buttress reduction in the treatment of young femoral neck fracture: A systematic review and meta-analysis.

BACKGROUND: Femoral neck fractures in young adults(<65 years), have always been a difficult problem, characterized by high rates of nonunion and avascular necrosis (AVN). The clinical efficacy of anatomical reduction and non-anatomical reduction methods needs to be supported by clinical data. Therefore, we conduct a meta-analysis on the clinical efficacy of different reduction methods to better guide clinical practice. METHODS: Relevant studies published using internal fixation to treat femoral neck fracture in several databases were searched. The outcomes sought included Harris score and the rate of AVN, nonunion and femoral neck shortening (<5 mm). Included studies were assessed for methodological bias and estimates of effect were calculated. Potential reasons for heterogeneity were explored. RESULTS: The clinical results showed that compared with the anatomical reduction and positive buttress, there is no significant difference in the rate of AVN (OR = 0.87, 95%CI: 0.55-1.37, P = .55), nonunion (OR = 0.54, 95%CI: 0.21-1.41, P = .21), femoral neck shortening (<5 mm) (OR = 1.03,95%CI: 0.57-1.86, P = .92), the Harris score (MD = -0.28, 95%CI: -1.36-0.80, P = .61) and the excellent and good rate of Harris score (OR = 1.73, 95%CI: 0.84-3.56, P = .61). However, compared with negative buttress, the rate of AVN (OR = 0.62, 95%CI: 0.38-1.01, P = .05), nonunion (OR = 0.34, 95%CI: 0.12-1.00, P = .05) and femoral neck shortening (<5 mm) (OR = 0.27, 95%CI: 0.16-0.45, P < .00001) were significantly lower, and the Harris score (MD = 6.53, 95%CI: 2.55 ~ 10.51, P = .001) was significantly better in positive buttress. CONCLUSIONS: In the case of difficult to achieve anatomical reduction, for young patients (< 65 years) with femoral neck fracture, reduction with positive buttress can be an excellent alternative and negative buttress should be avoided as much as possible.

Comparative analysis of the biological characteristics and mechanisms of azole resistance of clinical Aspergillus fumigatus strains.

Aspergillus fumigatus is a common causative pathogen of aspergillosis. At present, triazole resistance of A. fumigatus poses an important challenge to human health globally. In this study, the biological characteristics and mechanisms of azole resistance of five A. fumigatus strains (AF1, AF2, AF4, AF5, and AF8) were explored. There were notable differences in the sporulation and biofilm formation abilities of the five test strains as compared to the standard strain AF293. The ability of strain AF1 to avoid phagocytosis by MH-S cells was significantly decreased as compared to strain AF293, while that of strains AF2, AF4, and AF5 were significantly increased. Fungal burden analysis with Galleria mellonella larvae revealed differences in pathogenicity among the five strains. Moreover, the broth microdilution and E-test assays confirmed that strains AF1 and AF2 were resistant to itraconazole and isaconazole, while strains AF4, AF5, and AF8 were resistant to voriconazole and isaconazole. Strains AF1 and AF2 carried the cyp51A mutations TR34/L98H/V242I/S297T/F495I combined with the hmg1 mutation S541G, whereas strains AF4 and AF8 carried the cyp51A mutation TR46/Y121F/V242I/T289A, while strain AF5 had no cyp51A mutation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed differences in the expression levels of genes associated with ergosterol synthesis and efflux pumps among the five strains. In addition, transcriptomics, RT-qPCR, and the NAD+/NADH ratio demonstrated that the mechanism of voriconazole resistance of strain AF5 was related to overexpression of genes associated with energy production and efflux pumps. These findings will help to further elucidate the triazole resistance mechanism in A. fumigatus.

Prognostic factors for sublingual gland carcinoma: a population-based Surveillance, Epidemiology and End Results database study.

OBJECTIVE: To identify the clinical features and prognostic factors for sublingual gland carcinoma. METHODS: This was a case-control study. Patients with surgically treated sublingual gland carcinoma were retrospectively included in the Surveillance, Epidemiology and End Results database and divided into adenoid cystic carcinoma (ACC) and non-ACC groups. Primary outcome variables were disease-specific survival (DSS) and overall survival (OS). Prognostic factors for each group were analyzed using Cox models. RESULTS: We included 251 patients (115 men and 136 women). Compared with the non-ACC group, the ACC group had a larger average tumor size and received more adjuvant radiotherapy. In patients with ACC, the pathologic grade had an independent impact on DSS and OS, and patients who were undergoing adjuvant chemotherapy had worse DSS than those who were not receiving chemotherapy. In the non-ACC group, pathologic grade IV, lymph node metastasis, and adjuvant chemotherapy were associated with poor DSS and OS, and tumor extension predicted worsening DSS. CONCLUSIONS: In sublingual gland carcinoma, the pathologic grade and adjuvant chemotherapy were the most important prognostic factors, whereas lymph node metastasis had a negative impact in non-ACC patients but not in ACC patients.

Tough Interfacial Adhesion Enabled Extremely Durable Flexible Supercapacitors.

The interfacial void and delamination between the hydrogel electrolyte and flexible electrode caused by the inconformal contact and weak adhesion lead to serious performance degradation of solid-state-sandwiched supercapacitors (SCs) upon repetitive deformation. Herein, we propose a hydrogel polymer electrolyte (HPE) engineering strategy for enhancing the interfacial adhesion (Γ) to achieve extremely durable SCs via the soft, tough, and self-adhesive HPE. Using a self-cross-linked poly(N-hydroxyethyl acrylamide)/H3PO4 (PHEAA/H3PO4) HPE as the model, the interfacial adhesion between HPE and polyaniline (PANI)-modified carbon cloth (CC) electrode (CC/PANI) reaches up to 556 J/m2, leading to excellent durability of electrochemical performance under long-term repetitive deformations. The as-assembled sandwiched SC retains 94.14 and 93.62% of initial capacitance after 180° bending and twisting for 100,000 cycles, respectively. Furthermore, benefiting from the addition of H3PO4, the flexible sandwiched SC displays excellent tolerance to low temperatures and delivers a capacitance retention of 98.03% after 180° bending for 10,000 cycles at -20 °C. This work highlights the importance of interfacial adhesion engineering for the design of extremely deformation-tolerable SCs.

Cost-effectiveness analysis of antiretroviral drugs for treatment-naive HIV infection in China.

INTRODUCTION: Dolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China. METHODS: A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis. RESULTS: Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses. CONCLUSIONS: DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.

Population impact of fine particulate matter on tuberculosis risk in China: a causal inference.

BACKGROUND: Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 µm in diameter (PM2.5) and tuberculosis in China. METHODS: Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982-2019, annual provincial aggregated data during 1982-2019 and monthly provincial aggregated data during 2004-2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004-2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects. RESULTS: GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model. CONCLUSIONS: Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden.

Nasal Respiratory Epithelial Adenomatoid Hamartoma: Three Case Reports and Review of the Literature.

Hamartomas, as non-true tumors, are commonly found in the lungs, digestive tract, and kidneys, and there are few clinical reports on nasal cases. Nasal histiocytosis accompanied by lymphatic lesions is a common feature of nasal hamartoma. Three patients with nasal cavity hamartoma were treated in our department, including 1 male and 2 females, with nasal obstruction or epistaxis. The imaging (computed tomography, magnetic resonance imaging) of 2 patients showed a soft tissue mass in the nasal cavity and no erosion of bone, while in 1 patient, the imaging was inconclusive. The excised material in all patients was found to be a soft mass. The 3 cases showed the same pattern under histological examination, and all 3 patients were diagnosed with nasal cavity respiratory epithelial adenomatoid hamartoma (REAH). Nasal hamartoma is a rare disease with nonspecific clinical manifestations and imaging features and is often misdiagnosed. Only by a better understanding of this disease can the rate of correct clinical diagnosis be improved.

Adaptive neural network control for Markov jumping systems against deception attacks.

This paper proposes an innovative approach for mitigating the effects of deception attacks in Markov jumping systems by developing an adaptive neural network control strategy. To address the challenge of dual-mode monitoring mechanisms, two independent Markov chains are used to describe the state changes of the system and the intermittent actuator. By employing a mapping technique, these individual chains are amalgamated into a unified joint Markov chain. Additionally, to effectively approximate the unbounded false signals injected by deception attacks, an adaptive neural network technique is skillfully built. A mode monitoring scheme is implemented to design an asynchronous control law that links the mode information between the joint Markov chain and controller with fewer modes. The paper derives sufficient criteria for the mean-square bounded stability of the resulting system based on Lyapunov theories. Finally, a numerical experiment is conducted to demonstrate the effectiveness of the proposed method.

Bikunin: A Promising Prognostic Biomarker for Acute-on-Chronic Liver Failure in Patients with Viral Hepatitis B.

Purpose: To screen out potential prognostic biomarkers for HBV-related acute-on-chronic liver failure (HBV-ACLF). Patients and Methods: Peripheral blood samples of HBV-ACLF patients (n=56) and normal controls (n=15) from the Affiliated Hospital of Southwest Medical University from January 2021 to April 2022 were collected, 5 normal patients and 10 patients with ACLF were randomly selected for Data independent acquisition (DIA) mass spectrometry analysis, and the potential core proteins were screened out via bioinformatics. All samples were validated by Enzyme linked immunosorbent assays (ELISA) technology, and the survival curve was constructed based on the patient's 90-day survival time. Results: A total of 247 differentially expressed proteins (DEPs) were screened, of which 148 were upregulated and 99 were down-regulated. The DEPs were mainly enriched in high-density lipoprotein particle remodeling, coagulation, and hemostasis and participated in signaling pathways such as cholesterol metabolism, coagulation cascades, and PPAR signaling pathway. Finally, bikunin was selected for further study and validated via the ELISA, compared with the normal group, bikunin was poorly expressed in the HBV-ACLF group, the difference was statistically significant (P < 0.0001), the area under the curve (AUC) for Receiver operating characteristic (ROC) analysis was 0.917. Furthermore, compared with the non-survival group, bikunin was highly expressed in the HBV-ACLF survival group, the difference was statistically significant (P=0.0015), and the survival curve showed a positive correlation with patient survival (P=0.0063). Conclusion: The level of plasma bikunin in HBV-ACLF is down-regulated, which is positively correlated with the survival of the patients with HBV-ACLF, and is expected to become a new prognostic biomarker.

Neferine Attenuates HDM-Induced Allergic Inflammation by Inhibiting the Activation of Dendritic Cell.

House dust mite (HDM) acts as an environmental antigen that might cause chronic allergic diseases. Neferine (NEF) shows anti-inflammation therapeutic effects. This study is to explore the protection role of NEF against HDM-induced allergic inflammation. HDM-induced allergic asthmatic C57BL/6J mice models were established. Differential histological staining was used to analyze lung tissue pathological scores. Flow cytometry was used to analyze subtypes and biomarker expression of immune cells. RT-PCR and ELISA were used to test cytokines-related gene and/or protein expression levels. Western blot was performed to investigate the signaling pathway that mediates allergic inflammation from mice lung tissue and bone marrow-derived dendritic cells (BMDCs). H&E and PAS staining results indicate NEF significantly attenuated inflammatory index and the percentage of goblet cells in the lung tissue induced by HDM. The HDM-elevated TH2 and TH17 cells were significantly decreased by NEF; inflammatory cytokines Il-4, Il-13 and Il-17 were dramatically downregulated in the NEF plus HDM group compared with HDM alone. CD40+ and CD86+ DCs, eosinophils and mast cells, and ILC2 cells were decreased by NEF which was elevated under HDM stimulation. In vivo and ex vivo investigations indicated NEF can attenuate the activated NF-κB signaling induced by HDM is involved in allergic inflammatory immune response and regulates cytokines-related gene expression. HDM-activated DCs promoted differentiation of TH2 and TH17 cells but were attenuated by NEF. This study suggests NEF interrupts the overexpression of some cytokines released by DCs, TH2, and TH17 cells; NEF attenuates HDM-induced allergic inflammation via inhibiting NF-κB signaling of DCs.

HOXA13 promotes the proliferation, migration, and invasion of nasopharyngeal carcinoma HNE1 cells by upregulating the expression of Snail and MMP-2.

Homeobox A13 (HOXA13) has been verified as an oncogen in some malignancies. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. This study aims to explore the role of HOXA13 in NPC and its underlying mechanism. The mRNA expression of HOXA13 in NPC was obtained from the GSE53819 and GSE64634 datasets in the Gene Expression Omnibus (GEO) database. MTT, colony formation and transwell assays and xenograft tumour models were used to investigate the effects of HOXA13 on NPC HNE1 cells in vitro and in vivo. The expression of HOXA13, epithelial-mesenchymal transition-transcription factor (EMT-TF) Snail and matrix metalloproteinase 2 (MMP-2) was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The results showed that HOXA13 was upregulated in NPC. Silencing HOXA13 suppressed the proliferation, migration, and invasion of HNE1 cells, which inhibited tumour growth, while overexpression of HOXA13 induced the opposite effects. In addition, the expression of Snail and MMP-2 at the transcriptional and protein levels was associated with the expression of HOXA13. In summary, our results suggest that HOXA13 plays a role as a cancer-promoting gene in NPC. The underlying mechanism may be related to the upregulation of Snail and MMP-2.

Construction of High-Density Genetic Map and QTL Mapping for Grain Shape in the Rice RIL Population.

Grain shape is an important agronomic trait directly associated with yield in rice. In order to explore new genes related to rice grain shape, a high-density genetic map containing 2193 Bin markers (526957 SNP) was constructed by whole-genome resequencing of 208 recombinant inbred (RILs) derived from a cross between ZP37 and R8605, with a total genetic distance of 1542.27 cM. The average genetic distance between markers was 0.76 cM, and the physical distance was 201.29 kb. Quantitative trait locus (QTL) mapping was performed for six agronomic traits related to rice grain length, grain width, length-to-width ratio, thousand-grain weight, grain cross-sectional area, and grain perimeter under three different environments. A total of 39 QTLs were identified, with mapping intervals ranging from 8.1 kb to 1781.6 kb and an average physical distance of 517.5 kb. Among them, 15 QTLs were repeatedly detected in multiple environments. Analysis of the genetic effects of the identified QTLs revealed 14 stable genetic loci, including three loci that overlapped with previously reported gene positions, and the remaining 11 loci were newly identified loci associated with two or more environments or traits. Locus 1, Locus 3, Locus 10, and Locus 14 were novel loci exhibiting pleiotropic effects on at least three traits and were detected in multiple environments. Locus 14, with a contribution rate greater than 10%, influenced grain width, length-to-width ratio, and grain cross-sectional area. Furthermore, pyramiding effects analysis of three stable genetic loci showed that increasing the number of QTL could effectively improve the phenotypic value of grain shape. Collectively, our findings provided a theoretical basis and genetic resources for the cloning, functional analysis, and molecular breeding of genes related to rice grain shape.

Cost-effectiveness of cytomegalovirus vaccination for females in China: A decision-analytical Markov study.

BACKGROUND: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females. METHODS: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500). FINDINGS: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses. INTERPRETATION: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases.

Recent Advances in Molecular Mechanism and Breeding Utilization of Brown Planthopper Resistance Genes in Rice: An Integrated Review.

Over half of the world's population relies on rice as their staple food. The brown planthopper (Nilaparvata lugens Stål, BPH) is a significant insect pest that leads to global reductions in rice yields. Breeding rice varieties that are resistant to BPH has been acknowledged as the most cost-effective and efficient strategy to mitigate BPH infestation. Consequently, the exploration of BPH-resistant genes in rice and the development of resistant rice varieties have become focal points of interest and research for breeders. In this review, we summarized the latest advancements in the localization, cloning, molecular mechanisms, and breeding of BPH-resistant rice. Currently, a total of 70 BPH-resistant gene loci have been identified in rice, 64 out of 70 genes/QTLs were mapped on chromosomes 1, 2, 3, 4, 6, 8, 10, 11, and 12, respectively, with 17 of them successfully cloned. These genes primarily encode five types of proteins: lectin receptor kinase (LecRK), coiled-coil-nucleotide-binding-leucine-rich repeat (CC-NB-LRR), B3-DNA binding domain, leucine-rich repeat domain (LRD), and short consensus repeat (SCR). Through mediating plant hormone signaling, calcium ion signaling, protein kinase cascade activation of cell proliferation, transcription factors, and miRNA signaling pathways, these genes induce the deposition of callose and cell wall thickening in rice tissues, ultimately leading to the inhibition of BPH feeding and the formation of resistance mechanisms against BPH damage. Furthermore, we discussed the applications of these resistance genes in the genetic improvement and breeding of rice. Functional studies of these insect-resistant genes and the elucidation of their network mechanisms establish a strong theoretical foundation for investigating the interaction between rice and BPH. Furthermore, they provide ample genetic resources and technical support for achieving sustainable BPH control and developing innovative insect resistance strategies.