Prediction and Identification of Potential Immunodominant Epitopes in Glycoproteins B, C, E, G, and I of Herpes Simplex Virus Type 2

Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2), and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested via experiments in vitro. Among the 20 epitope peptides, 17 could react with the antisera to the corresponding parent proteins in the EIA tests. In particular, five peptides, namely, gB2466–473 (EQDRKPRN), gC2216–223 (GRTDRPSA), gE2483–491 (DPPERPDSP), gG2572–579 (EPPDDDDS), and gI2286-295 (CRRRYRRPRG) had strong reaction with the antisera. All conjugates of the five peptides with the carrier protein BSA could stimulate mice into producing antibodies. The antisera to these peptides reacted strongly with the corresponding parent glycoproteins during the Western Blot tests, and the peptides reacted strongly with the antibodies against the parent glycoproteins during the EIA tests. The antisera against the five peptides could neutralize HSV-2 infection in vitro, which has not been reported until now. These results suggest that the immunodominant epitopes screened using software algorithms may be used for virus diagnosis and vaccine design against HSV-2

The obesity paradox in osteoporosis risk among older adults is mostly driven by women:a population-based prospective study

Objectives: The obesity paradox is common among older adults at risk for various diseases. Although this paradox has also been observed in the association between obesity and osteoporosis, the available evidence remains controversial. This study aimed to investigate the association between obesity and OP risk in an older population. Methods: A cross-sectional and prospective study was conducted using data from 177,734 participants in the UK Biobank. The association of body mass index (BMI), waist circumference (WC), and fat percentage with BMD was examined using Spearman correlation analysis with baseline BMD data. Cox proportional hazards regression analysis was used to investigate the association between obesity and OP risk. Restricted cubic spline (RCS) were used to assess the nonlinear associations of BMI, WC, and fat percentage with OP. Results: Baseline cross-sectional analyses revealed a significant positive association between BMI, WC, and fat percentage with BMD in women, whereas this association was very weak in men. A total of 8,998 OP patients were identified during a median follow-up period of 13.7 years. Cox analyses showed that obesity as defined by BMI, WC, and fat percentage was associated with a 33%, 23%, and 31% reduction in the risk of OP in older women but not in men, respectively. Conjoint analysis showed that lower BMI was associated with increased risk of OP in older adults, whereas the lowest risk was observed in women with higher BMI and higher body fat. RCS revealed an inverse J-shaped nonlinear association between obesity metrics and OP risk in women. Conclusion: Lower BMI is an independent risk factor for OP in older adults, and the obesity paradox for OP risk exists only in women.</p

AFAP1-AS1 Promotes Epithelial-Mesenchymal Transition and Tumorigenesis Through Wnt/β-Catenin Signaling Pathway in Triple-Negative Breast Cancer

Long non-coding RNA (LncRNA) actin filament-associated protein1-antisense RNA 1 (AFAP1-AS1) is overexpressed in various types of cancers and plays an important role in tumor progression and prognosis. This study investigates the role of AFAP1-AS1 in tumor progression in triple-negative breast cancer (TNBC). We found that AFAP1-AS1 was overexpressed in TNBC tissues and cells. Overexpression of LncRNA AFAP1-AS1 was associated with poor prognosis in TNBC patients. Moreover, we demonstrated that upregulation of AFAP1-AS1 promoted cell proliferation and invasion, and inhibited cell apoptosis in vitro, while overexpression of AFAP1-AS1 promoted tumor growth in vivo. Our results also revealed that upregulation of AFAP1-AS1 activated Wnt/β-catenin pathway to promote tumorigenesis and cell invasion by increasing the expression of C-myc and epithelial-mesenchymal transition-related molecules in TNBC. Collectively, AFAP1-AS1 can be an independent prognostic marker and an effective therapeutic target of triple- negative breast cancer

Fungi and cercozoa regulate methane-associated prokaryotes in wetland methane emissions

Wetlands are natural sources of methane (CH4) emissions, providing the largest contribution to the atmospheric CH4 pool. Changes in the ecohydrological environment of coastal salt marshes, especially the surface inundation level, cause instability in the CH4 emission levels of coastal ecosystems. Although soil methane-associated microorganisms play key roles in both CH4 generation and metabolism, how other microorganisms regulate methane emission and their responses to inundation has not been investigated. Here, we studied the responses of prokaryotic, fungal and cercozoan communities following 5 years of inundation treatments in a wetland experimental site, and molecular ecological networks analysis (MENs) was constructed to characterize the interdomain relationship. The result showed that the degree of inundation significantly altered the CH4 emissions, and the abundance of the pmoA gene for methanotrophs shifted more significantly than the mcrA gene for methanogens, and they both showed significant positive correlations to methane flux. Additionally, we found inundation significantly altered the diversity of the prokaryotic and fungal communities, as well as the composition of key species in interactions within prokaryotic, fungal, and cercozoan communities. Mantel tests indicated that the structure of the three communities showed significant correlations to methane emissions (p &lt; 0.05), suggesting that all three microbial communities directly or indirectly contributed to the methane emissions of this ecosystem. Correspondingly, the interdomain networks among microbial communities revealed that methane-associated prokaryotic and cercozoan OTUs were all keystone taxa. Methane-associated OTUs were more likely to interact in pairs and correlated negatively with the fungal and cercozoan communities. In addition, the modules significantly positively correlated with methane flux were affected by environmental stress (i.e., pH) and soil nutrients (i.e., total nitrogen, total phosphorus and organic matter), suggesting that these factors tend to positively regulate methane flux by regulating microbial relationships under inundation. Our findings demonstrated that the inundation altered microbial communities in coastal wetlands, and the fungal and cercozoan communities played vital roles in regulating methane emission through microbial interactions with the methane-associated community

Tumor regression rate, PD-L1 expression, pembrolizumab/nab-paclitaxel–based regimens, squamous cell carcinoma, and comorbidities were independently associated with efficacy of neoadjuvant chemoimmunotherapy in non-small cell lung cancer

BackgroundNeoadjuvant chemoimmunotherapy (NCIO) is more effective than neoadjuvant immunotherapy alone for pathological response in non-small cell lung cancer (NSCLC) patients, but the processes for determining patient suitability for its implementation are not clear. We aimed to identify the most relevant factors and build a convenient model to select NSCLC patients who would benefit most from NCIO.Methods We retrospectively collected the clinical data of patients with locally advanced NSCLC who received NCIO followed by surgery at our institution between January 2019 and July 2022.ResultsA total of 101 eligible stage IIB-IIIC NSCLC patients were included. After NCIO, all patients successfully underwent surgical resection. A total of 46.53% (47/101) of patients achieved pathological complete response (pCR), and 70.30% (71/101) achieved major pathologic response (MPR). Tumor regression rate (adjusted odds ratio OR = 12.33), PD-L1 expression (adjusted odds ratio (OR) = 9.66), pembrolizumab/nab-paclitaxel–based regimens (adjusted OR = 4.92), and comorbidities (adjusted OR = 0.16) were independently associated with pCR rate (all P &lt; 0.05). Tumor regression rate (adjusted OR = 8.45), PD-L1 expression (adjusted OR = 5.35), and presence of squamous cell carcinoma (adjusted OR = 7.02) were independently associated with MPR rate (all P &lt; 0.05). We established and validated an easy-to-use clinical model to predict pCR (with an area under the curve [AUC] of 0.848) and MPR (with an AUC of 0.847). Of note, the present study showed that CD4+ T-cell count/rate and total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels in the peripheral blood of pre-NCIO patients were also significantly correlated with pathological response in univariate analyses.ConclusionsThe tumor regression rate, PD-L1 expression, pembrolizumab/nab-paclitaxel–based regimens, presence of squamous cell carcinoma, and comorbidities were the main influential factors for incidence of pCR/MPR in patients with stage IIB-IIIC NSCLC in the present study. Through predictive models, we can predict who will benefit most from NCIO prior to the emergence of clinical outcomes in locally advanced NSCLC

Co-composting of tail vegetable with flue-cured tobacco leaves: analysis of nitrogen transformation and estimation as a seed germination agent for halophyte

Resource utilization of tail vegetables has raised increasing concerns in the modern agriculture. However, the effect and related mechanisms of flue-cured tobacco leaves on the product quality, phytotoxicity and bacterially-mediated nitrogen (N) transformation process of tail vegetable composting were poorly understood. Amendments of high-dosed (5% and 10% w/w) tobacco leaves into the compost accelerated the heating process, prolonged the time of thermophilic stage, increased the peak temperature, thereby improving maturity and shortening composting duration. The tobacco leaf amendments at the 10% (w/w) increased the N conservation (TN and NH4-N content) of compost, due to the supply of N-containing nutrient and promotion of organic matter degradation by tobacco leaves. Besides, tobacco leaf amendments promoted the seed germination and root development of wild soybean, exhibiting the feasibility of composting product for promoting the growth of salt-tolerant plants, but no dose-dependent effect was found for tobacco leaf amendments. Addition of high dosed (5% and 10% w/w) tobacco leaves shifted the bacterial community towards lignocellulosic and N-fixing bacteria, contributing to increasing the compost maturity and N retention. PICRUSt 2 functional prediction revealed that N-related bacterial metabolism (i.e., hydroxylamine oxidation and denitrifying process) was enhanced in the tobacco leaf treatments, which contributed to N retention and elevated nutrient quality of composting. To the best knowledge, this was the first study to explore the effect of tobacco waste additives on the nutrient transformation and halophyte growth promotion of organic waste composting. These findings will deepen the understanding of microbially-mediated N transformation and composting processes involving flue-cured tobacco leaves

Adjuvant Chemotherapy Versus Adjuvant Concurrent Chemoradiotherapy After Radical Surgery for Early-Stage Cervical Cancer: A Randomized, Non-Inferiority, Multicenter Trial

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment

Research on control allocation, legality and acquisition performance of cross-border M&A based on stakeholder theory

As the involvement of Chinese enterprises in cross-border mergers and acquisitions (M&A) increases, on the one hand, it can drive enterprises to integrate with the international community and accelerate their transformation and upgrading, continuously enhancing their international competitiveness; on the other hand, it will also cause enterprises to experience more setbacks and challenges, especially the “weak acquisition of the strong” reverse cross-border acquisitions, which makes enterprises face a higher risk of failure. Reasonable control rights allocation can fully utilize the competitive advantages of enterprises, achieve synergistic cooperation among shareholders, board of directors, and management, promote the realization of enterprises’ cross-border acquisition goals, and thus enhance the value creation of acquisitions. There is a positive correlation between internal legitimacy and acquisition performance; the relevant assumptions about the distribution of shareholder control rights are invalid; the control rights at the board of directors level are negatively correlated with internal legitimacy and acquisition performance, and internal legitimacy has a mediating effect between the control rights at the board of directors level and acquisition performance, but the moderating effect of the acquisition mode is not significant; the control rights at the management level are negatively correlated with internal legitimacy and acquisition performance, and internal legitimacy has a mediating effect between the control rights at the management level and acquisition performance, and the acquisition mode negatively moderates the relationship between the control rights at the management level and internal legitimacy. This study takes the post-acquisition control rights allocation as the entry point, and examines the cross-border acquisition activities of Chinese enterprises from the perspective of stakeholders. The research results not only can enrich existing acquisition theory, but also can provide theoretical guidance for Chinese enterprise managers on allocation of control of target enterprises, and provide a theoretical basis for the state to formulate and optimize the system and policies of enterprises’ cross-border acquisitions

Research on control allocation, legality and acquisition performance of cross-border M&A based on stakeholder theory

As the involvement of Chinese enterprises in cross-border mergers and acquisitions (M&A) increases, on the one hand, it can drive enterprises to integrate with the international community and accelerate their transformation and upgrading, continuously enhancing their international competitiveness; on the other hand, it will also cause enterprises to experience more setbacks and challenges, especially the “weak acquisition of the strong” reverse cross-border acquisitions, which makes enterprises face a higher risk of failure. Reasonable control rights allocation can fully utilize the competitive advantages of enterprises, achieve synergistic cooperation among shareholders, board of directors, and management, promote the realization of enterprises’ cross-border acquisition goals, and thus enhance the value creation of acquisitions. There is a positive correlation between internal legitimacy and acquisition performance; the relevant assumptions about the distribution of shareholder control rights are invalid; the control rights at the board of directors level are negatively correlated with internal legitimacy and acquisition performance, and internal legitimacy has a mediating effect between the control rights at the board of directors level and acquisition performance, but the moderating effect of the acquisition mode is not significant; the control rights at the management level are negatively correlated with internal legitimacy and acquisition performance, and internal legitimacy has a mediating effect between the control rights at the management level and acquisition performance, and the acquisition mode negatively moderates the relationship between the control rights at the management level and internal legitimacy. This study takes the post-acquisition control rights allocation as the entry point, and examines the cross-border acquisition activities of Chinese enterprises from the perspective of stakeholders. The research results not only can enrich existing acquisition theory, but also can provide theoretical guidance for Chinese enterprise managers on allocation of control of target enterprises, and provide a theoretical basis for the state to formulate and optimize the system and policies of enterprises’ cross-border acquisitions

Road Network Pre-partitioning Method with Priority for Congestion Control

Urban traffic congestion seriously affects the traffic efficiency, causing travel delays and resources wasted directly. In this paper, a road network pre-partitioning method with priority for congestion control is proposed to reduce traffic congestion. Traffic flow feature is extracted based on CNN, and the estimated accuracy of intersection reach 95.32% through CNN-SVM model. Subarea congestion coefficient and intersection merger coefficient are defined to expand the control area of congestion coordination. The association and similarity of intersections are considered using spectral clustering for non-congested intersection partitioning. The results show that the congestion priority control partition method reduces a congestion intersection compared to directly using spectral clustering for subarea partition, and reduces the road network congestion coefficient by 0.05 after 30 minutes than directly using spectral clustering, which is an effective subarea partition method.  </jats:p