CaWRKY01-10 and CaWRKY08-4 Confer Pepper's Resistance to Phytophthora capsici Infection by Directly Activating a Cluster of Defense-Related Genes.

Phytophthora blight of pepper, which is caused by the notorious oomycete pathogen Phytophthora capsici, is a serious disease in global pepper production regions. Our previous study had identified two WRKY transcription factors (TFs), CaWRKY01-10 and CaWRKY08-4, which are prominent modulators in the resistant pepper line CM334 against P. capsici infection. However, their functional mechanisms and underlying signaling networks remain unknown. Herein, we determined that CaWRKY01-10 and CaWRKY08-4 are localized in plant nuclei. Transient overexpression assays indicated that both CaWRKY01-10 and CaWRKY08-4 act as positive regulators in pepper resistance to P. capsici. Besides, the stable overexpression of CaWRKY01-10 and CaWRKY08-4 in transgenic Nicotiana benthamiana plants also significantly enhanced the resistance to P. capsici. Using comprehensive approaches including RNA-seq, CUT&RUN-qPCR, and dual-luciferase reporter assays, we revealed that overexpression of CaWRKY01-10 and CaWRKY08-4 can activate the expressions of the same four Capsicum annuum defense-related genes (one PR1, two PR4, and one pathogen-related gene) by directly binding to their promoters. However, we did not observe protein-protein interactions and transcriptional amplification/inhibition effects of their shared target genes when coexpressing these two WRKY TFs. In conclusion, these data suggest that both of the resistant line specific upregulated WRKY TFs (CaWRKY01-10 and CaWRKY08-4) can confer pepper's resistance to P. capsici infection by directly activating a cluster of defense-related genes and are potentially useful for genetic improvement against Phytophthora blight of pepper and other crops.

Exploring Stigma Experience and Coping Strategies Among Women Living with HIV/AIDS in China: A Phenomenological Study.

Purpose: As of the end of 2022, over 20 million women worldwide, aged 15 and above, are living with HIV. Stigma remains a formidable barrier for women living with HIV/AIDS, hindering their access to healthcare and exacerbating health disparities. Indeed, some women living with HIV/AIDS can successfully confront and overcome stigma. There remains a paucity of qualitative research exploring the stigma coping strategies of women living with HIV/AIDS in China. This study was aimed to gain the deeper understanding of stigma experienced by women living with HIV/AIDS and coping strategies. Patients and Methods: We recruited diverse participants using snowball sampling and purposive sampling. Semi-structured personal in-depth interviews were conducted with 30 women living with HIV/AIDS from December 2022 to June 2023. The samples were from four HIV/AIDS designated hospitals. The data were analyzed using the Colaizzi seven-step model. Results: The experiences of stigma among women living with HIV/AIDS included family role (wife/mother/grandmother) collapse and disgusted by family, resignation in being shunned by others, helplessness due to social exclusion, grief at being devaluated, and resentment for experiencing injustice. The coping strategies used to deal with stigma included concealing their conditions, avoiding socialization, and attempting to retaliate against society. Conclusion: Healthcare professionals are recommended to offer women living with HIV/AIDS effective emotional support and guidance to cope with stigma. The study highlights the stigma they face, providing valuable evidence for policymakers. Recommendations emphasize the importance of developing services addressing both physical and psychological needs of women living with HIV/AIDS.

Corrigendum: Case report and literature analysis: Autoimmune cerebellar ataxia associated with homer-3 antibodies.

[This corrects the article DOI: 10.3389/fneur.2022.951659.].

The Effect of Magnetic Resonance Imaging Based Radiomics Models in Discriminating stage I-II and III-IVa Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common tumor in China. Accurate stages of NPC are crucial for treatment. We therefore aim to develop radiomics models for discriminating early-stage (I-II) and advanced-stage (III-IVa) NPC based on MR images. METHODS: 329 NPC patients were enrolled and randomly divided into a training cohort (n = 229) and a validation cohort (n = 100). Features were extracted based on axial contrast-enhanced T1-weighted images (CE-T1WI), T1WI, and T2-weighted images (T2WI). Least absolute shrinkage and selection operator (LASSO) was used to build radiomics signatures. Seven radiomics models were constructed with logistic regression. The AUC value was used to assess classification performance. The DeLong test was used to compare the AUCs of different radiomics models and visual assessment. RESULTS: Models A, B, C, D, E, F, and G were constructed with 13, 9, 7, 9, 10, 7, and 6 features, respectively. All radiomics models showed better classification performance than that of visual assessment. Model A (CE-T1WI + T1WI + T2WI) showed the best classification performance (AUC: 0.847) in the training cohort. CE-T1WI showed the greatest significance for staging NPC. CONCLUSION: Radiomics models can effectively distinguish early-stage from advanced-stage NPC patients, and Model A (CE-T1WI + T1WI + T2WI) showed the best classification performance.

Do Migrants Receive Tuberculosis Education in China? Evidence From the China Migrants Dynamic Survey.

BACKGROUND: Migrants are the key population for tuberculosis (TB) transmission in China. However, it remains unknown how many migrants have received TB education and through what means. OBJECTIVES: To identify the rate and methods of TB education among migrants in China by using nationally representative data. METHOD: This study used secondary data analysis. The data were derived from the China Migrants Dynamic Survey 2014-2017. A total sample of 745,926 migrants was included in the following analysis. Information on TB education was collected through a self-report questionnaire. We used hierarchical logistic regression models to explore the relationship between the independent variables and the receipt of TB education. RESULTS: Only 30.4% (n = 226,458) received TB education. Among all age-groups, participants between 65 and 69 years old had the highest TB education rate (33.4%). Bulletin boards (86.5%-91%), media (73% to 86.7%), and books/magazines (59.2%-67.4%) were the most common ways for migrants to receive TB education. CONCLUSIONS: Our study showed the rates of TB education in each region of China and indicated the significant disparity among the seven regions. Traditional media, off-line medical consultation, community advocacy, and bulletin boards should be the primary methods of delivering TB education. TB education campaigns targeting migrants with a low socioeconomic status should be actively promoted.

MRI radiomics-based machine learning model integrated with clinic-radiological features for preoperative differentiation of sinonasal inverted papilloma and malignant sinonasal tumors.

Objective: To explore the best MRI radiomics-based machine learning model for differentiation of sinonasal inverted papilloma (SNIP) and malignant sinonasal tumor (MST), and investigate whether the combination of radiomics features and clinic-radiological features can produce a superior diagnostic performance. Methods: The database of 247 patients with SNIP (n=106) or MST (n=141) were analyzed. Dataset from scanner A were randomly divided into training set (n=135) and test set 1 (n=58) in a ratio of 7:3, and dataset from scanner B and C were used as an additional independent test set 2 (n=54). Fourteen clinic-radiological features were analyzed by using univariate analysis, and those with significant differences were applied to construct clinical model. Based on the radiomics features extracted from single sequence (T2WI or CE-T1WI) and combined sequence, four commonly used classifiers (logistic regression (LR), support vector machine (SVM), decision tree (DT) and k-nearest neighbor (KNN)) were employed to constitute twelve different machine learning models, and the best-performing one was confirmed as the optimal radiomics model. Furthermore, a combined model incorporated best radiomics feature subsets and clinic-radiological features was developed. The diagnostic performances of these models were assessed by the area under the receiver operating characteristic (ROC) curve (AUC) and the calibration curves. Results: Five clinic-radiological features (age, convoluted cerebriform pattern sign, heterogeneity, adjacent bone involvement and infiltration of surrounding tissue) were considered to be significantly different between the tumor groups (P < 0.05). Among the twelve machine learning models, the T2WI-SVM model exhibited optimal predictive efficacy for classification tasks on the two test sets, with the AUC of 0.878 and 0.914, respectively. For three types of diagnostic models, the combined model achieved highest AUC of 0.912 (95%CI: 0.807-0.970) and 0.927 (95%CI: 0.823-0.980) for differentiation of SNIP and MST in test 1 and test 2 sets, which performed prominently better than clinical model (P=0.011, 0.005), but not significantly different from the optimal radiomics model (P=0.100, 0.452). Conclusion: The machine learning model based on T2WI sequence and SVM classifier achieved best performance in differentiation of SNIP and MST, and the combination of radiomics features and clinic-radiological features significantly improved the diagnostic capability of the model.

Case report and literature analysis: Autoimmune cerebellar ataxia associated with homer-3 antibodies.

Objective: We present a case of autoimmune cerebellar ataxia (ACA) associated with Homer protein homolog 3 (Homer-3) antibodies. Then, a review of the literature was conducted to summarize its clinical spectrum to improve clinicians' understanding of this rare entity. Case presentation: A 25-year-old man suffered from the subacute onset of cerebellar ataxia and psychiatric symptoms with abnormalities in the cerebellum on initial brain MRI and Homer-3 antibodies titers of 1:100 in the serum. His neurological symptoms did not improve after intravenous methylprednisolone but significantly improved following plasma exchange with a modified Rankin Scale (mRS) score of 1. However, 5 months later, he experienced relapse during oral prednisone tapering with enhanced cerebellar lesions and obvious cerebellar atrophy on repeated MRI. Various immunomodulatory approaches, including corticosteroids and plasma exchange, were utilized with no improvement. Then rituximab was given for the first time to treat Homer-3 autoimmunity with partial improvement of symptoms. However, the patient remained profoundly disabled with an mRS score of 4. Conclusion: ACA associated with Homer-3 antibodies may have a suboptimal response to corticosteroid therapy. More intense immunotherapy such as rituximab may contribute to the improvement of cerebellar syndrome. Relapsing courses and presentation of cerebellar atrophy may suggest a poor prognosis in this entity.

Steady-State Based Model of Airborne Particle/Gas and Settled Dust/Gas Partitioning for Semivolatile Organic Compounds in the Indoor Environment.

Indoor semivolatile organic compounds (SVOCs), present in the air, airborne particles, settled dust, and other indoor surfaces, can enter the human body through several pathways. Knowing the partitioning between gaseous and particulate phases is important in identifying specific pathway contributions and thereby accurately assessing human exposure. Numerous studies have developed equilibrium equations to predict airborne particle/gas (P/G) partitioning in air (KP) and dust/gas (D/G) partitioning in settled dust (KD). The assumption that P/G and D/G equilibria are instantaneous for airborne and settled dust phases, commonly adopted by current indoor fate models, is not likely valid for compounds with high octanol-air partition coefficients (KOA). Here, we develop steady-state based equations to predict KP and KD in the indoor environment. Results show that these equations perform well and are verified by worldwide monitoring data. It is suggested that instantaneous steady state could work for P/G and D/G partitioning of SVOCs in indoor environments, and the equilibrium is just a special case of the steady state when log KOA < 11.38 for P/G partitioning and log KOA < 10.38 for D/G partitioning. These newly developed equations and methods provide a tool for more accurate assessment for human exposure to SVOCs in the indoor environment.

Mycobacterium vaccae Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.

Increased Internal Carotid Artery Tortuosity is a Risk Factor for Spontaneous Cervicocerebral Artery Dissection.

OBJECTIVE: Spontaneous cervicocerebral artery dissection (sCCD) is an important cause of ischaemic stroke that often occurs in young and middle aged patients. The purpose of this study was to investigate the correlation between tortuosity of the carotid artery and sCCD. METHODS: Patients with confirmed sCCD who underwent computed tomography angiography (CTA) were reviewed retrospectively. Age and sex matched patients having CTA were used as controls. The tortuosity indices of the cervical arteries were measured from the CTA images. The carotid siphon and the extracranial internal carotid artery (ICA) were evaluated according to morphological classification. The carotid siphons were classified into five types. The extracranial ICA was categorised as simple tortuosity, coiling or kinking. Independent risk factors for sCCD were investigated using multivariable analysis. RESULTS: The study included sixty-six patients with sCCD and 66 controls. There were no differences in vascular risk factors between the two groups. The internal carotid tortuosity index (ICTI) (25.24 ± 12.37 vs. 15.90 ± 8.55, respectively; p < .001) and vertebral tortuosity index (VTI) (median 11.28; interquartile range [IQR] 6.88, 18.80 vs. median 8.38; IQR 6.02, 12.20, respectively; p = .008) were higher in the patients with sCCD than in the controls. Type III and Type IV carotid siphons were more common in the patients with sCCD (p = .001 and p < .001, respectively). The prevalence of any vessel tortuosity, coiling and kinking of the extracranial ICA was higher in the patients with sCCD (p < .001, p = .018 and p = .006, respectively). ICTI (odds ratio [OR] 2.964; p = .026), VTI (OR 5.141; p = .009), and Type III carotid siphons (OR 4.654; p = .003) were independently associated with the risk of sCCD. CONCLUSION: Arterial tortuosity is associated with sCCD, and greater tortuosity of the cervical artery may indicate an increased risk of arterial dissection.

Elevated repulsive guidance molecule-a mRNA in peripheral blood mononuclear cells are associated with impaired leptomeningeal collaterals in patients with middle cerebral artery occlusions.

BACKGROUND: In the event of middle cerebral artery occlusion (MCAO), leptomeningeal collaterals (LMCs) play a crucial role in determining the survival of brain tissue distal to occlusion. Previous findings indicated that genes controlling arteriogenesis can impact the extent of LMCs. Therefore, probe for potential genetic parameters correlating of arteriogenesis may be clinically useful in predicting LMCs status in MCAO. During the screening process, we focused on repulsive guidance molecule a (RGMa), which has been reported to play a negative role in angiogenesis after stroke by decreasing the proliferation, migration, and tube formation of endothelial cells (ECs) in vivo and in vitro. Indeed, endothelial function plays a main role in arteriogenesis and is essential in determining the LMCs status. Therefore, in present study, we aimed to testify the hypothesis that RGMa might be associated with LMCs status in MCAO. METHODS: We prospectively enrolled patients with acute M1 MCA +/- intracranial internal carotid artery (ICA) occlusions (n=96) and healthy controls (n=33). Status of LMCs was evaluated according to computed tomographic angiography (CTA) on admission. Baseline RGMa mRNA expression was quantified by using quantitative real-time PCR. RESULTS: Patients with poor LMCs showed significantly higher RGMa mRNA levels than patients with good LMCs status (P=0.001) as well as healthy controls (P=0.002), respectively; whereas good LMCs group showed similar baseline RGMa levels than controls (P=1.000). RGMa mRNA level and baseline NIHSS score were independent predictors for impaired LMCs. CONCLUSIONS: In MCAO patients, elevated PBMCs RGMa mRNA levels were associated with impaired LMCs status, indicating that measurement of RGMa mRNA expression in the early phase of stroke, together with other clinical approaches, was logically expected to be useful for predicting LMCs status. Moreover, a role for RGMa in leptomeningeal arteriogenesis following ischemic stroke can be hypothesized.

[Clinical study of artesunate in the treatment of coronavirus disease 2019].

OBJECTIVE: To discuss the effective of artesunate in the treatment of coronavirus disease 2019 (COVID-19). METHODS: Using prospective method, the 43 cases of confirmed COVID-19 patients in Nanning Fourth People's Hospital from January 22nd to February 15th in 2020 were enrolled and divided into routine treatment group (n = 25) and artesunate treatment group (n = 18) by odd-even rule after admission. According to the guidelines, the routine treatment group was recommended to receive lopinavir/ritonavir 500 mg + α-aerosolized interferon 500×104 U, twice daily; the artesunate treatment group was given artesunate 60 mg, twice daily besides the routine treatment, for 10 days in both groups. During the treatment period, the pharynx swab test of 2019 novel coronavirus (2019-nCoV) nucleic acid was carried out every 2 days, and the routine blood test, liver and kidney functions, blood coagulation function and myocardial enzymes were re-examined. Chest CT was checked every 3 days after the treatment, and re-examined every 5 days after the condition was improved. The routine blood test and biochemical results of two groups were observed, and the efficacy evaluation was performed by monitoring the time for significant improvement of symptoms, negative conversion time of throat swab virus nucleic acid, lung lesion absorption time, adverse drug reactions and the length of hospital stay of the two groups. RESULTS: There were no significant differences between the two groups in terms of gender, age, body weight, routine blood test and biochemical results before treatment. In artesunate treatment group, the time for significant improvement of symptoms (days: 3.33±1.91 vs. 4.84±2.19), negative conversion time of 2019-nCoV nucleic acid (days: 4.72±2.16 vs. 6.68±3.76), lung lesion absorption starting time (days: 5.39±2.36 vs. 7.48±3.78), lung lesion absorption greater than 70% time (days: 14.11±4.16 vs. 17.04±4.42) and the length of hospital stay (days: 16.56±3.71 vs. 18.04±3.97) were significantly shorter than those in routine treatment group, with significant differences (all P < 0.05). The incidence of adverse drug reactions in two groups had no significant difference (72.2% vs. 80.0%, P > 0.05). CONCLUSIONS: Artesunate can shorten the treatment time of COVID-19, improve prognosis and eliminate pathogens, with fewer adverse reactions and a good application prospect.