bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis
Authors: Nabeta Henry W. , Lasnik Amanda B. , Fuqua Joshua L. , Wang Lin , Rohan Lisa C. , Palmer Kenneth E.
Published: October 2022

Resistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in Nicotiana benthamiana. Griffithsin has well characterized broad spectrum antiviral activity and has demonstrated potent in vitro activity against multiple strains of Candida, including C. albicans. We have been working to incorporate Q-GRFT into topical microbicide products to prevent HIV-1 and HSV-2 transmission. The goal of this study was to evaluate the efficacy of a prototype Q-GRFT dosage form in prophylactic and therapeutic murine models of vaginal candidiasis, through microbiologic, histopathologic, and immune studies. In a preventive model, in comparison with infected controls, Q-GRFT treatment resulted in a lower fungal burden but did not alter the number of vaginal neutrophils and monocytes. In a therapeutic model, Q-GRFT enhanced fungal clearance when compared with infected untreated controls. Finally, histopathology demonstrated lower vaginal colonization with C. albicans following Q-GRFT treatment. Our results demonstrate that Q-GRFT has significant preventive and therapeutic activity in vaginal candidiasis offering additional benefit as a topical microbicide for prevention of HIV-1 and HSV-2 transmission.
Assessing the optimal uses of biomass: Carbon and energy price conditions for the Aines Principle to apply
Authors: Woodall Caleb M. , McCormick Colin F.
Published: October 2022

In the context of climate mitigation, biomass has traditionally been viewed as a means to deliver low-carbon energy products. Adding carbon capture and sequestration (CCS) to a bioenergy production process can yield net-removals of CO2 from the atmosphere, albeit at an increased cost. Recently, the Aines Principle was established, stating that at some carbon price, the revenue generated from CO2 removal will exceed the revenue generated from energy production from a given bioconversion process. This principle has only been illustrated for the theoretical conversion of a non-specific biomass source, and has not yet been demonstrated to show real carbon prices that can tip the scale for biomass carbon removal to be more economically favorable than bioenergy production. In this study, we demonstrate the Aines Principle at work in two specific examples of biomass conversion. The first case involves a Chinese municipal solid waste incineration plant, with and without CCS. The second case compares using forestry residue solely for energy production (via gasification), solely for carbon removal (via burial) or both. By comparing the energy and carbon revenue streams under a range of carbon prices, we show that carbon removal revenue can exceed energy revenue at currently available carbon prices below $200/tCO2.
Case report: Acute ST-elevation myocardial infarction and cardiogenic shock caused by a giant right sinus of Valsalva aneurysm and right coronary artery compression
Authors: Ma Lianyue , Yang Jianmin , Liu Yan , Wang Fang , Liu Tongtao , Wang Ying , Sun Hourong , Zhang Cheng , Zhang Yun
Published: October 2022

A sinus of Valsalva aneurysm (SVA) is a rare aortic disease that may be congenital or acquired. Patients with an intact SVA are usually asymptomatic, whereas a ruptured SVA may cause acute chest pain and dyspnea. We present a rare case of acute ST-elevation myocardial infarction and cardiogenic shock in a 51-year-old man. Emergency coronary angiography revealed a giant aneurysm with an absence of flow in the right coronary artery. Both two-dimensional echocardiography and computed tomography angiography showed a giant right SVA, which ruptured into the pericardial sac and led to extrinsic compression of the right coronary artery. Surgical repair combined with coronary bypass grafting was performed. Unfortunately, the patient died from low cardiac output syndrome and postoperative multiple organ failure. This case highlights that the possibility of SVA rupture should be considered in acute myocardial infarction cases and that echocardiography and coronary computed tomography angiography are important in providing an accurate and rapid SVA diagnosis.
One-stage hybrid coronary revascularization for the treatment of multivessel coronary artery disease— Periprocedural and long-term results from the “HYBRID-COR” feasibility study
Authors: Sanetra Krzysztof , Buszman Piotr Paweł , Jankowska-Sanetra Justyna , Cisowski Marek , Fil Wojciech , Gorycki Bogdan , Bochenek Andrzej , Slabon-Turska Monika , Konopko Marta , Kaźmierczak Paweł , Gerber Witold , Milewski Krzysztof , Buszman Paweł Eugeniusz
Published: October 2022

Background

The constant growth of interest in hybrid coronary artery revascularization (HCR) is apparent. Yet, few studies report outcomes of the one-stage HCR. Consequently, the status of such procedures is not adequately supported in clinical guidelines. The aim of this study was to report the safety, feasibility, and long term-outcomes of the one-stage HCR.

Methods and results

Patients were enrolled in the prospective one-stage hybrid coronary revascularization program (HYBRID-COR). They underwent a one-stage hybrid revascularization procedure while on double antiplatelet therapy (DAPT) with Ticagrelor: endoscopic atraumatic coronary artery bypass grafting (EACAB) for revascularization of the left anterior descending (LAD) artery and percutaneous intervention in non-LAD arteries with contemporary drug-eluting stents. The composite primary endpoint included MACCE (major adverse cardiac and cerebrovascular events: death, myocardial infarction, stroke, and repeated revascularization) in long-term observation. The study cohort consisted of 30 patients (68% male) with stable coronary artery disease (26.7%) and unstable angina (73.3%). Procedural success was 100%. No death, myocardial infarction (MI), or stroke were observed in the perioperative period. One patient (3.3%) required chest revision and blood transfusion due to surgical bleeding. Kidney injury was noted in two patients (6.6%). In a long-term follow-up (median; IQR: 4.25; 2.62–4.69 years), two patients (6.6%) underwent repeated revascularization and one patient (3.3%) died due to MI. The overall primary endpoint rate was 9.9%.

Conclusion

One-stage hybrid revascularization, on DAPT, is a feasible, safe, and efficient way of achieving complete revascularization in selected patients. The complication rate is low and acceptable. Further randomized trials are required.
Validation of plasma D-dimer in Chinese patients with acute non-ST segment elevation myocardial infarction
Authors: Fan Xin , Min Tingting , Su Shaohui , Xiong Bin , Wan Huaibin
Published: October 2022

Objective

To analyze the predictive values of D-dimer in Chinese patients with non-ST-segment elevation myocardial infarction (NSTEMI).

Methods

We retrospectively retrieved consecutive patients hospitalized due to acute NSTEMI from January 2015 to December 2018 from the Electronic Medical Record (EMR) library. Clinical and follow-up data were collected. The primary endpoint was major adverse composite cardiovascular events (MACEs), such as all-cause death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints included all-cause death, non-fatal myocardial infarction, non-fatal stroke, heart failure, and severe arrhythmias. The Cox regression model was used to evaluate the association between risk factors and clinical outcomes in Chinese patients with NSTEMI.

Results

A total of 673 patients were included; the median age was 64.0 (53.0–75.0) years old and 76.2% were men. Patients with higher D-dimer levels were more often women, older, had a higher Charlson Comorbidity Index, and had a higher incidence of MACEs (59.9 vs. control 9.0%; p < 0.001) and all-cause death (49.1 vs. control 2.2%; p < 0.001). The multivariate Cox analysis suggested that the D-dimer level was an independent predictor of MACEs (hazard ratio [HR]: 1.069, 95% CI: 1.010–1.132, p = 0.021). The receiver operating characteristic (ROC) analysis suggested that D-dimer levels were better than the Charlson Comorbidity Index in all-cause death.

Conclusion

In Chinese patients with acute NSTEMI, higher D-dimer levels on admission suggest a poor long-term prognosis.
Percutaneous coronary intervention in patients with cancer using bare metal stents compared to drug-eluting stents
Authors: Ahmed Talha , Pacha Homam Moussa , Addoumieh Antoine , Koutroumpakis Efstratios , Song Juhee , Charitakis Konstantinos , Boudoulas Konstantinos Dean , Cilingiroglu Mehmet , Marmagkiolis Konstantinos , Grines Cindy , Iliescu Cezar A.
Published: October 2022

Background

Management of coronary artery disease (CAD) is unique and challenging in cancer patients. However, little is known about the outcomes of using BMS or DES in these patients. This study aimed to compare the outcomes of percutaneous coronary intervention (PCI) in cancer patients who were treated with bare metal stents (BMS) vs. drug-eluting stents (DES).

Methods

We identified cancer patients who underwent PCI using BMS or DES between 2013 and 2020. Outcomes of interest were overall survival (OS) and the number of revascularizations. The Kaplan–Meier method was used to estimate the survival probability. Multivariate Cox regression models were utilized to compare OS between BMS and DES.

Results

We included 346 cancer patients who underwent PCI with a median follow-up of 34.1 months (95% CI, 28.4–38.7). Among these, 42 patients were treated with BMS (12.1%) and 304 with DES (87.9%). Age and gender were similar between the BMS and DES groups (p = 0.09 and 0.93, respectively). DES use was more frequent in the white race, while black patients had more BMS (p = 0.03). The use of DES was more common in patients with NSTEMI (p = 0.03). The median survival was 46 months (95% CI, 34–66). There was no significant difference in the number of revascularizations between the BMS and DES groups (p = 0.43). There was no significant difference in OS between the BMS and DES groups in multivariate analysis (p = 0.26). In addition, independent predictors for worse survival included age > 65 years, BMI ≤ 25 g/m2, hemoglobin level ≤ 12 g/dL, and initial presentation with NSTEMI.

Conclusions

In our study, several revascularizations and survival were similar between cancer patients with CAD treated with BMS and DES. This finding suggests that DES use is not associated with an increased risk for stent thrombosis, and as cancer survival improves, there may be a more significant role for DES.
Association between Rab31/rs9965664 polymorphism and immunoglobulin therapy resistance in patients with Kawasaki disease
Authors: Yu Hongyan , Lin Yueling , Xu Yufen , Chen Kaining , Wang Yishuai , Fu Lanyan , Zhou Huazhong , Pi Lei , Che Di , Qiu Xiantao , Gu Xiaoqiong
Published: October 2022

Background

Kawasaki disease (KD) is an acute febrile systemic vasculitis affecting infants and young children. A high dose of intravenous immunoglobulin (IVIG) is the first-line strategy for patients with KD to reduce persistent inflammation and the risk of coronary artery aneurysm (CAA) formation. Unfortunately, 10–20% of the patients showed no response to the treatment and were defined as resistant to IVIG. Rab31 has been reported to regulate innate immunity in several human diseases. However, whether single nucleotide polymorphism (SNP) in Rab31 gene could predispose to IVIG therapy response in KD was uncovered.

Methods

Rab31/rs9965664 polymorphism was genotyped in 1,024 Chinese patients with KD through TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between Rab31/rs9965664 polymorphism and IVIG therapeutic effects.

Results

Our results showed that Rab31/rs9965664 AA/GA genotype was significantly associated with an increased risk of IVIG resistance compared to GG genotype (GA vs. GG: p = 0.0249; AA vs. GG: p = 0.0016; AA/GA vs. GG: p = 0.0039; and AA vs. GG/GA: p = 0.0072). Moreover, the KD individuals carrying the rs9965664 A allele displayed lower Rab31 protein levels, and the expression level of Rab31 in the IVIG-resistant group was decreased significantly when compared to that observed in the response group. A mechanical study demonstrated that Rab31 modulated IVIG response through NLRP3 and p38 pathways.

Conclusion

These results suggested that Rab31/rs9965664 polymorphism might be associated with an increased risk of IVIG resistance in southern Chinese patients with KD. The possible mechanism is that Rab31 regulates the NLRP3 pathway negatively to inhibit IVIG response.
Early de-cannulation from extracorporeal membrane oxygenation following ventricular tachycardia radiofrequency ablation
Authors: Sabbag Avi , Nissan Johnatan , Beinart Roy , Sternik Leonid , Kassif Igal , Kogan Alexander , Ram Eilon , Nof Eyal
Published: October 2022

Objectives

Ventricular tachycardia ablation (VTA) with hemodynamic compromise presents a challenge. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support allows the safe completion of the procedure. There are limited data regarding the safety of weaning off VA-ECMO at the end of the procedure. We report our experience with early VA-ECMO de-cannulation after VTA.

Materials and methods

All patients undergoing VA-ECMO-assisted VTA, between January 2013 and December 2020 at a large tertiary center were included. Clinical characteristics, history of arrhythmia, procedural details, and outcomes were collected. Patients weaned from VA-ECMO immediately at the end of the procedure were compared to those that were de-cannulated at a later time.

Results

A total of 46 patients (93.5% male, age 62 ± 10 years) were ablated with VA-ECMO support. Most had ischemic cardiomyopathy (65%) and (70%) presented with VT storm. The clinical VT was induced in the majority of patients (76%). A total of 99 VTs were induced of which 76 (77%) were targeted and successfully ablated. Non-inducibility was achieved in 74% of cases and most patients (83%) were de-cannulated at the end of the procedure on the procedure table. Survival at 1 year was higher among early de-cannulated patients (86 vs. 38% [log-rank p-value < 0.001]). At 1-year follow-up, 91.3% of surviving patients were free of appropriate ICD shocks.

Conclusion

De-cannulation from VA-ECMO may be done immediately at the conclusion of VTA in most cases. Failure to timely wean off VA-ECMO is a strong predictor of mortality.
Putting external validation performance of major bleeding risk models into context
Authors: Blacketer Clair , Reps Jenna M. , Wang Lu , Ryan Patrick B. , Yuan Zhong
Published: October 2022

When developing predictive models, model simplicity and performance often need to be balanced. We propose a novel methodology to put the performance of bleeding risk prediction models ORBIT, ATRIA, HAS-BLED, CHADS2, and CHA2DS2-VASc into perspective. Instead of comparing the existing models’ performance against the 0.5–1 AUROC scale, we suggest estimating a prediction task specific AUROC scale, lower bound AUROC (lbAUROC) and upper bound AUROC (ubAUROC), to help assess the balance between model simplicity and performance and determine whether more complex models could significantly improve the ability to predict the outcome. We validate the existing bleeding risk prediction models by applying them to a cohort of new users of warfarin and a cohort of new users of direct oral anticoagulants (DOACs) separately, across a set of four observational databases. Then, we develop the lbAUROC-ubAUROC scale by using the validation data to train regularized logistic regression models. The internal validation AUROC of the model that includes only age and gender variables was used to estimate the lbAUROC. The internal validation AUROC of the model that includes thousands of candidate variables was used to estimate the ubAUROC. The age and gender only models achieved AUROCs between 0.50 and 0.56 (lower bound) and the large-scale models achieved AUROCs between 0.67 and 0.72 and between 0.70 and 0.77 (upper bound) within the target cohorts of warfarin new users and DOACs new users, respectively. The AUROC of existing bleeding risk prediction models fall between the upper-bound and lower-bound of predictive models. Our study showed that this context of the predictability of the outcome is essential when evaluating risk prediction models to be administered in actual practice.
The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review
Authors: Feng Jiaxing , He Hui , Wang Yu , Zhang Xu , Zhang Xiuying , Zhang Tiantian , Zhu Mengyi , Wu Xiaoke , Zhang Yuehui
Published: October 2022

Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility.
Menopause and development of Alzheimer’s disease: Roles of neural glucose metabolism and Wnt signaling
Authors: Villaseca Paulina , Cisternas Pedro , Inestrosa Nibaldo C.
Published: October 2022

Late onset Alzheimer´s disease (AD) is a neurodegenerative disease with gender differences in its onset and progression, being the prevalence predominant in women and at an earlier age than in men. The pathophysiology of the menopausal condition has been associated to this dementia, playing major roles regarding both endocrine and glucose metabolism changes, amongst other mechanisms. In the current review we address the role of estrogen deficiency in the processes involved in the development of AD, including amyloid precursor protein (APP) processing to form senile plaques, Tau phosphorylation forming neurofibrillary tangles, Wnt signaling and AD neuropathology, the role of glucose brain metabolism, Wnt signaling and glucose transport in the brain, and our research contribution to these topics.
Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus
Authors: Lv Hehe , Zhang Fan , Liang Can , Liu Xuekui , Ma Yamei , Li Jiayi , Ye Yan , Si Shanwen , Liu Yaran , Heng Hao , Geng Houfa
Published: October 2022

The discovery of a large number of small pulmonary nodules and early diagnosis of lung cancer in the diabetic patients prompt us to re-examine the relationship between diabetes and the occurrence and development of lung cancer. The aim of this study was to explore the underlying metabolites changes in diabetes with NSCLC or benign nodule patients, and further to investigate the association of serum IGF-1 level and differentially expressed metabolites (DEMs). An untargeted metabolomics method was used to detect the changes of metabolism in diabetic patients with NSCLC on the platform of HR-MS. Serum level of IGF-1 was measured by ELISA. The patients were divided to three groups, DM, DLB (nodule), and DLC (cancer). we have identified numerous DEMs, which include amino acid, choline, and fatty acid derivatives. Further analysis of the involved metabolic pathways suggested that linoleate metabolism, tryptophan metabolism, histidine metabolism, putative anti-Inflammatory metabolites formation from EPA, and arachidonic acid metabolism were considered to be the most significant metabolic pathways between groups. Networks analysis suggested that a series of metabolites were associated with serum IGF-1among the three groups, which can be divided into 6 categories. Nine metabolites have been identified as the main DEMs among the DLC, DLB, and DM groups. In conclusion, metabolomics is a powerful and promising tool for the cancer risk evaluation in diabetic patients. Our results suggest that decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.
Human FSH Glycoform α-Subunit Asparagine52 Glycans: Major Glycan Structural Consistency, Minor Glycan Variation in Abundance
Authors: Butnev Viktor Y. , May Jeffrey V. , Brown Alan R. , Sharma Tarak , Butnev Vladimir Y. , White William K. , Harvey David J. , Bousfield George R.
Published: October 2022

Follicle-stimulating hormone (FSH), an α/β heterodimeric glycoprotein hormone, consists of functionally significant variants resulting from the presence or absence of either one of two FSHβ subunit N-glycans. The two most abundant variants are fully-glycosylated FSH24 (based on 24 kDa FSHβ band in Western blots) and hypo-glycosylated FSH21 (21 kDa band, lacks βAsn24 glycans). Due to its ability to bind more rapidly to the FSH receptor and occupy more FSH binding sites than FSH24, hypo-glycosylated FSH21 exhibits greater biological activity. Endoglycosidase F1-deglycosylated FSH bound to the complete extracellular domain of the FSH receptor crystallized as a trimeric complex. It was noted that a single biantennary glycan attached to FSHα Asn52 might preemptively fill the central pocket in this complex and prevent the other two FSH ligands from binding the remaining ligand-binding sites. As the most active FSH21 preparations possessed more rapidly migrating α-subunit bands in Western blots, we hypothesized that Asn52 glycans in these preparations were small enough to enable greater FSH21 receptor occupancy in the putative FSHR trimer model. Highly purified hFSH oligosaccharides derived from each FSH subunit, were characterized by electrospray ionization-ion mobility-collision-induced dissociation (ESI-IM-CID) mass spectrometry. FSHβ glycans typically possessed core-linked fucose and were roughly one third bi-antennary, one third tri-antennary and one third tetra-antennary. FSHα oligosaccharides largely lacked core fucose and were bi- or tri-antennary. Those αAsn52 glycans exhibiting tetra-antennary glycan m/z values were found to be tri-antennary, with lactosamine repeats accounting for the additional mass. Selective αAsn52 deglycosylation of representative pituitary hFSH glycoform Superdex 75 gel filtration fractions followed by ESI-IM-CID mass spectrometry revealed tri-antennary glycans predominated even in the lowest molecular weight FSH glycoforms. Accordingly, the differences in binding capacity of the same receptor preparation to different FSH glycoforms are likely the organization of the FSH receptor in cell membranes, rather than the αAsn52 oligosaccharide.
Androgens improve ovarian follicle function impaired by glucocorticoids through an androgen-IGF1-FSH synergistic effect
Authors: Gao Lingyun , Gao Hongna , Wang Wenjun
Published: October 2022

High concentrations of glucocorticoids caused by chronic stress are known to affect ovarian function and cause diminished ovarian reserve. Androgens are essential for early-stage ovarian follicle development, but the effects and mechanisms of androgens on follicle development under chronic stress remain unclear. In this study, we aim to investigate the effects of high concentrations of glucocorticoids on the function of in vitro cultured ovarian cells and mouse early-stage ovarian follicles and to validate the hypothesis that androgen–insulin-like growth factor 1 (IGF1)–follicle-stimulating hormone (FSH) synergistic signaling helps to ameliorate the damage caused by high concentrations of glucocorticoids. KGN cells (human granulosa cell line) and mouse primary cells were treated with different concentrations of glucocorticoids, and the cell proliferation, apoptosis, and sex hormone secretion were detected. The effects of glucocorticoid and androgens on IGF1 receptor (IGF1R) and FSH receptor (FSHR) expression in KGN cells were detected by Western blot. Steroidogenic synthase expressions under androgens and androgen-IGF1-FSH combination treatment were examined by qPCR after manipulation using low and high concentrations of glucocorticoids. The mechanism of androgen regulation of IGF1R and FSHR was explored by small interfering RNA (siRNA) and chromatin immunoprecipitation (ChIP)-qPCR. Damage of glucocorticoids and the treatment effects of androgens were further validated in mouse ovarian follicles cultured in vitro. The results demonstrated that prolonged treatment with high-dose glucocorticoids reduced cell viability of granulosa cells, inhibited their sex hormone secretion, and impaired their sensitivity to IGF1 and FSH signaling by affecting IGF1R and FSHR functions. Androgens at an appropriate dose range improved early-stage follicle development and their hormone secretion under high-dose glucocorticoid treatment, which was related to increased transcription of Igf1r and Fshr. This work showed that excessive glucocorticoids impaired ovarian function and validated that balanced concentrations of androgens synergized with IGF1 and FSH to improve the function of early-stage ovarian follicles under conditions of chronic stress.
The fitting effects between strategic flexibility and managerial ties on green innovation in new ventures
Authors: Chen Haowen
Published: October 2022

Green innovation is a key variable in coordinating economic growth and ecological protection, and also the fundamental driving force for future economic development. Green innovation plays a crucial role in creating competitive advantages for companies. This paper investigates the impact of the interaction between strategic flexibility and managerial ties on green innovation in new firms, and explores ways to match strategic flexibility and managerial ties that are more appropriate for conducting green innovation practices. The results of the empirical study by using survey data from Chinese new firms indicate that different types of strategic flexibility and managerial ties can generate different synergies and thus have different impacts on green innovation. Specifically, for a new venture, it is more likely to use its ties with government to develop green innovation when it has greater resource flexibility. Conversely, a new venture with greater coordination flexibility is more capable of implementing green innovation through close ties with other firms. Our theoretical constructs and empirical results can better explain how different types of strategic flexibility use different kinds of managerial relationships to promote green innovation in new ventures.
Landslide susceptibility mapping based on the coupling of two correlation methods and the BP neural network model: A case study of the Baihetan Reservoir area, China
Authors: Xue Zhenghai , Feng Wenkai , Li Botao , Zhou Yongjian , Yi Xiaoyu , Wu Mingtang
Published: October 2022

The correlation calculation model between landslide and mapping factors has a direct influence on the accuracy of landslide susceptibility mapping results. Using the Baihetan reservoir area as a case study, the effect of several correlation models on mapping landslide susceptibility is studied. The frequency ratio (FR) and the information value (IV) coupled BP neural network (BPNN) model was utilized to assess landslide susceptibility, with the mapping results of the single back propagation neural network (BPNN) model acting as a reference. The receiver operating characteristic (ROC) curve, the frequency ratio, and the susceptibility index distribution (mean value and standard deviation) are used to compare and assess landslide susceptibility values. The FR-BPNN coupling model is less precise than the IV-BPNN model. Findings from a single BPNN model for susceptibility mapping are less exact than those from a coupled model. Using the coupling model of the mapping factor correlation approach to assess landslide susceptibility has evident benefits, according to the study. The coupled model employing IV as the correlation method provides the most accurate and dependable susceptibility findings, and the mapping results are more consistent with the actual distribution of landslides in the study area. It can effectively direct disaster prevention efforts in the reservoir region.
Accelerated catalytic ozonation for aqueous nitrobenzene degradation over Ce-loaded silicas: Active sites and pathways
Authors: Wang Qinghong , Ji Yuanyuan , Hu Jingze , Ye Huangfan , Liu Ya , Wang Yuxian , Chen Chunmao , Li Zhuoyu
Published: October 2022

Cerium oxides loaded silica catalysts were synthesized by an impregnation method by simply mixing Ce precursor with silica spherule (Ce/SS) and ordered MCM-41 zeolites (Ce/MCM-41), followed by a mild calcination. Compared with pure SS and MCM-41, Ce modified Ce/SS and Ce/MCM-41 demonstrate much improved catalytic ozonation activities for mineralization of recalcitrant nitrobenzene (NB). At solution pH of 6, 86 and 97% TOC mineralization rates were achieved within 60 min for Ce/MCM-41 and Ce/SS, respectively. Characterization results suggest that Ce loading significantly increases the surface Lewis acidic sites, which would synergize with Ce3+/Ce4+ redox cycle for the activity improvement. With the aid of in situ electron paramagnetic resonance (EPR) spectra and quenching tests, hydroxyl radical (·OH), superoxide radical (O2•–), and singlet oxygen (1O2) are identified as the O3 catalytic decomposition products, while ·OH mainly accounts for NB mineralization. The detailed degradation route of NB was further investigated by the multi-chromatography analysis. NB is firstly oxidized into polyhydroxy compounds, followed by small molecular organic acids, and finally being mineralized into CO2 and H2O. This study established a facile strategy to synthesize highly active and stable Ce/SiO2 catalysts for catalytic ozonation, and elucidated the in-depth mechanisms for the activity origins of the Ce loaded silica-based materials in catalytic ozonation processes (COP).
How does public infrastructure construction influence CO2 emissions? A global case
Authors: Qian Yichen , Sun Renjin , Zhao Jun , Song Sasa , Wang Pinchen
Published: October 2022

To empirically investigate as to whether and how public infrastructure influences the global greenhouse effect, this study utilizes a panel dataset of 35 countries over the period 2003–2019 for regression estimation. Furthermore, regional heterogeneous and mediation effects between infrastructure and carbon dioxide (CO2) emissions are explored. The primary findings insist that: 1) at the global level, public infrastructure is positive associated with CO2 emissions. In other words, strengthening infrastructure at this stage is not conducive to mitigating the greenhouse effect; 2) public infrastructure construction development in Belt and Road Initiative (BRI) countries has a greater positive impact on CO2 emissions than in non-BRI countries; and 3) the mediation roles of industrial upgrading and trade openness are established; specifically, trade openness and industrial upgrading are valid transmission routes through which public infrastructure affects CO2 emissions. Based on the above three findings, a number of policy implications related to accelerate low-carbon construction of infrastructure and promote industrial upgrading are proposed.
KRAS is a prognostic biomarker associated with diagnosis and treatment in multiple cancers
Authors: Zhao Da , Wang Lizhuang , Chen Zheng , Zhang Lijun , Xu Lei
Published: October 2022

KRAS encodes K-Ras proteins, which take part in the MAPK pathway. The expression level of KRAS is high in tumor patients. Our study compared KRAS expression levels between 33 kinds of tumor tissues. Additionally, we studied the association of KRAS expression levels with diagnostic and prognostic values, clinicopathological features, and tumor immunity. We established 22 immune-infiltrating cell expression datasets to calculate immune and stromal scores to evaluate the tumor microenvironment. KRAS genes, immune check-point genes and interacting genes were selected to construct the PPI network. We selected 79 immune checkpoint genes and interacting related genes to calculate the correlation. Based on the 33 tumor expression datasets, we conducted GSEA (genome set enrichment analysis) to show the KRAS and other co-expressed genes associated with cancers. KRAS may be a reliable prognostic biomarker in the diagnosis of cancer patients and has the potential to be included in cancer-targeted drugs.
Case report: Prenatal diagnosis of fetal intracranial hemorrhage due to compound mutations in the JAM3 gene
Authors: Xu Min , Jin Pengzhen , Huang Yingzhi , Qian Yeqing , Lin Miaochun , Zuo Juan , Zhu Jin , Li Zhaohui , Dong Minyue
Published: October 2022

Intracranial hemorrhage is a common complication in preterm infants but occasionally occurs in fetuses. Disruptions of the genes, such as the COL4A1 and COL4A2 genes, are common genetic causes identified in fetal intracranial hemorrhage; however, the disruptions of the JAM3 gene are rarely reported. In the current investigation, fetal intracranial hemorrhage and dilated lateral ventricles were observed in three consecutive siblings in a pedigree. The pregnancies were terminated, and whole-exome sequencing, followed by Sanger sequencing, was performed on the affected fetuses. Pre-implantation genetic testing for monogenic diseases was performed to avoid the recurrence. The compound heterozygous variants of c.712 + 2T > A and c.813C > G p.Tyr271* in the JAM3 gene (NM_032801.4) were identified in the proband and its affected brother, which were predicted to be pathogenic. The variant of c.813C > G p.Tyr271* but not c.712 + 2T > A was identified in the fourth fetus, implying a good prognosis. Our findings expanded the spectrum of the pathogenic mutations in the JAM3 gene and revealed an important application of fetal whole-exome sequencing in idiopathic fetal intracranial hemorrhage.
Driving down malaria transmission with engineered gene drives
Authors: Garrood William T. , Cuber Piotr , Willis Katie , Bernardini Federica , Page Nicole M. , Haghighat-Khah Roya E.
Published: October 2022

The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female Anopheles mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs. The utility of genetically engineered gene drive mosquitoes as tools to decrease the burden of malaria by controlling the disease-transmitting mosquitoes is being evaluated. To date, there has been remarkable progress in the development of CRISPR/Cas9-based homing endonuclease designs in malaria mosquitoes due to successful proof-of-principle and multigenerational experiments. In this review, we examine the lessons learnt from the development of current CRISPR/Cas9-based homing endonuclease gene drives, providing a framework for the development of gene drive systems for the targeted control of wild malaria-transmitting mosquito populations that overcome challenges such as with evolving drive-resistance. We also discuss the additional substantial works required to progress the development of gene drive systems from scientific discovery to further study and subsequent field application in endemic settings.
Identification of a novel gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment in osteosarcoma
Authors: Zheng Di , Xia Kezhou , Wei Zhun , Wei Zicheng , Guo Weichun
Published: October 2022

Ferroptosis is a novel form of non-apoptotic cell death that mainly results from the iron-dependent lethal accumulation of lipid peroxidation products. Here, we defined differentially expressed genes between control and RSL3-treated osteosarcoma cells as ferroptosis-associated genes (FAGs). These FAGs were then subjected to weighted gene correlation network analysis (WGCNA), and we found that the turquoise module, containing 71 FAGs, was markedly related to the patient’s vital status. After that, FAGs in the turquoise module were utilized to construct a prognostic multigene (COL5A2, HOXB4, and UNC5B) signature for risk stratification in osteosarcoma. Validation in internal and external cohorts indicated the accuracy and clinical applicability of this signature in predicting the prognosis of patients with osteosarcoma. Univariate and multivariate Cox regression analyses suggested that the signature-derived risk score is an independent indicator of patient prognosis. Immunological analysis indicated that significant variations in stromal and ESTIMATE scores, as well as tumor purity, were found when the high- and low-risk groups were compared. Regarding immune cell infiltration, the proportion of activated CD4 memory T cells was significantly lower in the high-risk group than that in the low-risk group. The ssGSEA results suggested that CD8+ T, Tfh, and Th1 cell scores were consistently lower in the high-risk group than those in the low-risk group. In terms of immune-related activities, the high-risk group had considerably lower scores for promoting inflammation, T-cell co-inhibition, and T-cell co-stimulation than the low-risk group, indicating the differential immunological state of the high- and low-risk groups. Of the three FAGs included in the signature, the expression of COL5A2, HOXB4, and UNC5B was higher in the high-risk groups, and the expression of COL5A2 and UNC5B was negatively associated with patient prognosis. Additionally, the mRNA levels of COL5A2 and HOXB4 were lower and those of UNC5B were higher in RSL3-treated cells than in control cells. In all, we systematically analyzed the transcriptional changes of osteosarcoma cells induced by RSL3 and constructed a novel three-gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment. We also identified COL5A2, HOXB4, and UNC5B as potential therapeutic targets and important regulators of ferroptosis in osteosarcoma.
Dissection of a grain yield QTL from wild emmer wheat reveals sub-intervals associated with culm length and kernel number
Authors: Deblieck Mathieu , Szilagyi Gergely , Andrii Fatiukha , Saranga Yehoshua , Lauterberg Madita , Neumann Kerstin , Krugman Tamar , Perovic Dragan , Pillen Klaus , Ordon Frank
Published: October 2022

Genetic diversity in wheat has been depleted due to domestication and modern breeding. Wild relatives are a valuable source for improving drought tolerance in domesticated wheat. A QTL region on chromosome 2BS of wild emmer wheat (Triticum turgidum ssp. dicoccoides), conferring high grain yield under well-watered and water-limited conditions, was transferred to the elite durum wheat cultivar Uzan (T. turgidum ssp. durum) by a marker-assisted backcross breeding approach. The 2B introgression line turned out to be higher yielding but also exhibited negative traits that likely result from trans-, cis-, or linkage drag effects from the wild emmer parent. In this study, the respective 2BS QTL was subjected to fine-mapping, and a set of 17 homozygote recombinants were phenotyped at BC4F5 generation under water-limited and well-watered conditions at an experimental farm in Israel and at a high-throughput phenotyping platform (LemnaTec-129) in Germany. In general, both experimental setups allowed the identification of sub-QTL intervals related to culm length, kernel number, thousand kernel weight, and harvest index. Sub-QTLs for kernel number and harvest index were detected specifically under either drought stress or well-watered conditions, while QTLs for culm length and thousand-kernel weight were detected in both conditions. Although no direct QTL for grain yield was identified, plants with the sub-QTL for kernel number showed a higher grain yield than the recurrent durum cultivar Uzan under well-watered and mild drought stress conditions. We, therefore, suggest that this sub-QTL might be of interest for future breeding purposes.
Fasting glucose mediates the influence of genetic variants of SOD2 gene on lean non-alcoholic fatty liver disease
Authors: Wu Na , Zhai Xiangyu , Yuan Fan , Li Jie , Yu Ning , Zhang Fengwei , Li Dong , Wang Jianying , Zhang Lei , Shi Yi , Ji Guang , He Guang , Liu Baocheng
Published: October 2022

Background: Non-alcoholic fatty liver disease (NAFLD) imposes an enormous burden on public health, and a large proportion of NAFLD patients are lean with normal body weight, which is rarely mentioned. We conducted this study to determine the mediation effects of fasting glucose on the relationships between genetic variants of SOD2 and the susceptibility of lean NAFLD in the elderly Chinese Han population.

Methods: Data in this manuscript were collected in a cross-sectional study among 5,387 residents (aged ≥60 years) in the Zhangjiang community center, Shanghai, China, in 2017. Ten (single nucleotide polymorphisms) SNPs previously reported to be related to NAFLD and obesity, including rs9939609, rs1421085, rs9930506, rs626283, rs641738, rs4880, rs58542926, rs738409, rs2281135, and rs2294918 were genotyped. The associations between genetic variations in SOD2 and fasting glucose in five genetic models were analyzed with the SNPassoc R package and rechecked with regression analysis. Mediation models were conducted to explore whether fasting glucose can mediate the association between SNPs and the susceptibility of lean NAFLD.

Results: In this study, lean NAFLD individuals had a higher waist circumference and waist-to-hip ratio, ALT, and fasting glucose than lean non-NAFLD individuals (p < 0.050). In comparison, the AA genotypic frequency of rs4880 in SOD2 gene was much lower in lean NAFLD patients (p = 0.005). And rs4800 had a significant indirect effect on lean NAFLD incidence mediated by fasting glucose (p < 0.001).

Conclusion: For the first time, the mediation effect of fasting glucose on the association of rs4880 in SOD2 with the susceptibility of lean NAFLD was clarified in the elderly Chinese Han population. It emphasized the connection between glucose homeostasis and oxidative stress in the mechanisms of lean NAFLD.
A novel prognostic model based on six methylation-driven genes predicts overall survival for patients with clear cell renal cell carcinoma
Authors: Zhou Hongmin , Xie Tiancheng , Gao Yuchen , Zhan Xiangcheng , Dong Yunze , Liu Ding , Xu Yunfei
Published: October 2022

Clear cell renal cell carcinoma (ccRCC) is a lethal urological malignancy. DNA methylation is involved in the regulation of ccRCC occurrence and progression. This study aimed to establish a prognostic model based on DNA methylation to predict the overall survival (OS) of patients with ccRCC. To create this model, we used the transcriptome and DNA methylation data of patients with ccRCC from The Cancer Genome Atlas (TCGA) database. We then used the MethylMix R package to identify methylation-driven genes, and LASSO regression and multivariate Cox regression analyses established the prognostic risk model, from which we derived risk scores. We incorporated these risk scores and clinical parameters to develop a prognostic nomogram to predict 3-, 5-, and 7-year overall survival, and its predictive power was validated using the ArrayExpress cohort. These analyses identified six methylation-driven genes (SAA1,FUT6,SPATA18,SHROOM3,AJAP1, andNPEPL1) that produced risk scores, which were sorted into high- and low-risk patient groups. These two groups differed in nomogram-predicted prognosis, the extent of immune cell infiltration, tumor mutational burden, and expected response to additional therapies. In conclusion, we established a nomogram based on six DNA methylation-driven genes with excellent accuracy for prognostic prediction in ccRCC patients. This nomogram model might provide novel insights into the epigenetic mechanism and individualized treatment of ccRCC.
Soluble mediators in the function of the epidermal-immune-neuro unit in the skin
Authors: Oleszycka Ewa , Kwiecien Kamila , Kwiecinska Patrycja , Morytko Agnieszka , Pocalun Natalia , Camacho Michelle , Brzoza Piotr , Zabel Brian A. , Cichy Joanna
Published: October 2022

Skin is the largest, environmentally exposed (barrier) organ, capable of integrating various signals into effective defensive responses. The functional significance of interactions among the epidermis and the immune and nervous systems in regulating and maintaining skin barrier function is only now becoming recognized in relation to skin pathophysiology. This review focuses on newly described pathways that involve soluble mediator-mediated crosstalk between these compartments. Dysregulation of these connections can lead to chronic inflammatory diseases and/or pathologic conditions associated with chronic pain or itch.
Transcriptomics and quantitative proteomics reveal changes after second stimulation of bone marrow-derived macrophages from lupus-prone MRL/lpr mice
Authors: Chen Keyue , Wu Tiyun , Wang Danyan , Li Rong , Shen Xiangfeng , Zhao Ting , Ozato Keiko , Li Rongqun
Published: October 2022

Innate immune memory can cause the occurrence and exacerbation of autoimmune diseases, and it is as well as being strongly associated with the pathogenesis of systemic lupus erythematosus (SLE), however, the specific mechanism remains to be further studied. We learned that IFN-γ stimulation generated innate immune memory in bone marrow-derived macrophages (BMDMs) and activated memory interferon-stimulated genes (ISGs). This research used IFN-γ and lipopolysaccharide (LPS) to treat BMDMs with lupus-prone MRL/lpr mice and showed that particular memory ISGs were substantially elevated in prestimulated macrophages. In order to identify the differentially expressed genes (DEGs), researchers turned to RNA-seq. GO and KEGG analysis showed that up-regulated DEGs were enriched in defense and innate immune responses, and were related to the expression of pattern recognition receptors (PRRs)-related pathways in macrophages. TMT-based proteome analysis revealed differentially expressed proteins (DEPs) up-regulated in BMDMs were abundant in metabolic pathways such as glucose metabolism. Our study found that after the secondary stimulation of MRL/lpr mice, the expression of PRRs in innate immune cells was changed, and IFN-related pathways were activated to release a large number of ISGs to promote the secondary response. At the same time, related metabolic modes such as glycolysis were enhanced, and epigenetic changes may occur. Therefore, SLE is brought on, maintained, and worsened by a variety of factors that work together to produce innate immune memory.