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BackgroundPercutaneous coronary intervention for in-stent restenosis (ISR) chronic total occlusion (CTO) has been a great challenge. There are occasions when the balloon is uncrossable or undilatable (BUs) even though the guidewire has passed, leading to failure of the procedure. Few studies have focused on the incidence, predictors, and management of BUs during ISR-CTO intervention.MethodsPatients with ISR-CTO were recruited consecutively between January 2017 and January 2022 and divided into two groups based on the presence of BUs. The clinical data of the two groups (BUs group and non-BUs group) were retrospectively analyzed and compared to explore the predictors and clinical management strategies of BUs.ResultsA total of 218 patients with ISR-CTO were included in this study, 23.9% (52/218) of whom had BUs. The percentage of ostial stents, stent length, CTO length, the presence of proximal cap ambiguity, moderate to severe calcification, moderate to severe tortuosity, and J-CTO score were higher in the BUs group than in the non-BUs group (p p p = 0.031), the presence of moderate to severe calcification (OR: 3.383, 95% CI: 1.628–5.921, p = 0.024) and moderate to severe tortuosity (OR: 4.816, 95% CI: 2.038–7.772, p = 0.033) were independent predictors of BUs.ConclusionThe initial rate of BUs in ISR-CTO was 23.9%. Ostial stents, presence of moderate to severe calcification, and moderate to severe tortuosity were independent predictors of BUs.

Horizontally transferred genes (HTGs) play a key role in animal symbiosis, and some horizontally transferred genes or proteins are highly expressed in specialized host cells (bacteriocytes). However, it is not clear how HTGs are regulated, but microRNAs (miRNAs) are prime candidates given their previously demonstrated roles in symbiosis and impacts on the expression of host genes. A horizontally acquired PanBC that is highly expressed in whitefly bacteriocytes can cooperate with an obligate symbiont Portiera for pantothenate production, facilitating whitefly performance and Portiera titre. Here, we found that a whitefly miRNA, novel-m0780-5p, was up-regulated and its target panBC was down-regulated in Portiera-eliminated whiteflies. This miRNA was located in the cytoplasmic region of whitefly bacteriocytes. Injection of novel-m0780-5p agomir reduced the expression of PanBC in whitefly bacteriocytes, while injection of novel-m0780-5p antagomir enhanced PanBC expression. Agomir injection also reduced the pantothenate level, Portiera titre and whitefly performance. Supplementation with pantothenate restored Portiera titre and the fitness of agomir-injected whiteflies. Thus, we demonstrate that a whitefly miRNA regulates panBC-mediated host-symbiont collaboration required for pantothenate synthesis, benefiting the whitefly-Portiera symbiosis. Both panBC and novel-m0780-5p are present in the genomes of six Bemisia tabaci species. The expression of a novel miRNA in multiple B. tabaci species suggests that the miRNA evolved after panBC acquisition, and allowed this gene to be more tightly regulated. Our discovery provides the first account of a HTG being regulated by a miRNA from the host genome, and suggests key roles for interactions between miRNAs and HTGs in the functioning of symbiosis.

EGFR blocking antibodies are approved for the treatment of colorectal cancer and head and neck squamous cell carcinoma (HNSCC). Although ERBB3 signaling has been proposed to limit the effectiveness of EGFR inhibitors, the underlying molecular mechanisms are not fully understood. To gain insight into these mechanisms, we generated potent blocking antibodies against ERBB3 (REGN1400) and EGFR (REGN955). We show that EGFR and ERBB3 are coactivated in multiple HNSCC cell lines and that combined blockade of EGFR and ERBB3 inhibits growth of these cell lines more effectively than blockade of either receptor alone. Blockade of EGFR with REGN955 strongly inhibited activation of ERK in HNSCC cell lines, whereas blockade of ERBB3 with REGN1400 strongly inhibited activation of Akt; only the combination of the 2 antibodies blocked both of these essential downstream pathways. We used a HER2 blocking antibody to show that ERBB3 phosphorylation in HNSCC and colorectal cancer cells is strictly dependent on association with HER2, but not EGFR, and that neuregulin 1 activates ERBB3/HER2 signaling to reverse the effect of EGFR blockade on colorectal cancer cell growth. Finally, although REGN1400 and REGN955 as single agents slowed the growth of HNSCC and colorectal cancer xenografts, the combination of REGN1400 plus REGN955 caused significant tumor regression. Our results indicate that activation of the Akt survival pathway by ERBB3/HER2 limits the effectiveness of EGFR inhibition, suggesting that REGN1400, which is currently in a phase I clinical trial, could provide benefit when combined with EGFR blocking antibodies. Mol Cancer Ther; 13(5); 1345–55. ©2014 AACR.

PDF - 78K, Effect of REGN1400 and REGN955 on ligand-induced signaling by ERBB3 and EGFR, respectively.

PDF - 56K, Measurement of REGN1400 and REGN955 binding affinities.

Intracellular heritable symbionts have been incorporated into insect reproductive and developmental biology by various mechanisms. All Bemisia tabaci species harbor the obligate symbiont Portiera in specialized insect cells called bacteriocytes. We report that the whitefly juvenile hormone and Portiera determined vitellogenin (Vg) localization in bacteriocytes of whiteflies.

Background Periprocedural myocardial injury (PMI) is associated with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). However, the incidence predictors and prognosis of PMI in chronic total occlusion (CTO) undergoing PCI remains unclear. Method To evaluate the predictors and prognostic impact of PMI following PCI in patients with CTO. We consecutively enrolled 132 individuals and 8 of whom with procedural failure were excluded in this study. Thus, a total of 124 CTO patients successfully received PCI were included in this study. And patients were divided into the PMI group (n = 42) and the non-PMI group (n = 82) according to their c-TnI levels measured after procedure. The baseline and angiographic characteristics of the two groups were compared. The predictors of PMI and the correlation between PMI and MACE were investigated. Results Overall, PMI occurred in 42 patients (33.9%). Comparing with control group, PMI group had more diabetes (54.8% vs. 31.7%,P = 0.013) and dyslipidemia (54.8% vs. 13.4%, P＜0.001). Also, there were significant differences between the two groups in left ventricular ejection fraction(43.2 ± 7.2 vs 47.2 ± 8.0, P = 0.027), prior myocardial infarction(54.8%vs43.1%, P = 0.020), prior PCI(57.1% vs 22.0%, P＜0.001) and prior CABG(14.3% vs 2.4%, P = 0.011). Also, patients with PMI had more calcified lesions (52.4% vs 24.4%, P = 0.002) and were more likely to have multivessel disease (71.4% vs 35.4%, P＜0.001). In addition, patients in the PMI group had higher J-CTO scores (3.3 ± 1.0 vs 1.9 ± 0.5, P＜0.001) and were more likely to have wire-crossing difficulties (64.3% vs 37.8%, P = 0.005), require more use of retrograde approach (38.1% vs 7.3%, P＜0.001) and have more procedural complications (19.0% vs 2.4%, P = 0.003). In the multivariate analysis, multivessel artery disease (odd ratio [OR], 4.347;95% confidence interval [CI], 1.601– 11.809;P = 0.004), retrograde approach (OR, 4.036; 95%CI, 1.162– 14.020;P = 0.028) and the presence of procedural complications (OR, 16.480;95%CI, 2.515-107.987;P = 0.003) were predictors of PMI. Conclusion The incidence of PMI in CTO patients after PCI was 33.9%. Multivessel artery disease, retrograde approach, and the presence of procedural complications were predictors of PMI after CTO-PCI. Patients who develop PMI tend to have a poorer clinical prognosis and more MACE than those who do not develop PMI.

Background: Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio), a new marker of inflammation, is associated with adverse cardiovascular events, but its relationship with coronary slow flow phenomenon (CSFP) is unclear. Therefore, we aimed to investigate the relationship between SII and CSFP. Methods: We enrolled consecutive patients who presented with chest pain, with normal/near-normal coronary angiography findings (n=89 as CSFP group; n=167 as control group). The baseline characteristics, laboratory parameters and angiographic characteristics of the two groups were compared. Results: SII levels were significantly higher in the CSFP group than in the control group (409.7 ± 17.7 vs. 396.7 ± 12.7, p < 0.001). A significant positive correlation between SII and the mean thrombolysis in myocardial infarction frame count (mTFC) was found (r = 0.624, p 404.29 was a predictor of CSFP with 67.4% sensitivity and 71.9% specificity. Conclusions: SII can predict the occurrence of CSFP.

Background Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio), a new marker of inflammation, is associated with adverse cardiovascular events, but its relationship with coronary slow flow phenomenon (CSFP) is unclear. Therefore, we aimed to investigate the relationship between SII and CSFP. Methods We enrolled consecutive patients who presented with chest pain, with normal/near-normal coronary angiography findings (n = 89 as CSFP group; n = 167 as control group). The baseline characteristics, laboratory parameters and angiographic characteristics of the two groups were compared. Results SII levels were significantly higher in the CSFP group than in the control group (409.7 ± 17.7 vs. 396.7 ± 12.7, p p p 404.29 was a predictor of CSFP with 67.4% sensitivity and 71.9% specificity. Conclusions SII can predict the occurrence of CSFP.

Sex differences in the long-term prognosis of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing alcohol septal ablation (ASA) remain unclear, especially in the Chinese Han population.This cohort study included 320 HOCM Chinese Han patients who underwent ASA because of symptomatic left ventricular outflow tract (LVOT) obstruction. Patients were grouped according to sex: females (mean±standard deviation age [SD] 50.7±6.8 years) and males (mean±SD age 52.6±7.3 years). Individuals were followed over the long term.Pre-procedure, women had more symptoms (New York Heart Association [NYHA] class III-IV 67.3% vs 56.3%, p=0.03), more atrial fibrillation (23.5% vs 14.6%, p=0.047) than men. Transient complete atrioventricular block after ASA was more common in woman than in men (34.0 vs 23.4%; p=0.048). Residual LVOT gradient, post-procedural residual left ventricular wall thickness, NYHA functional class, and adverse arrhythmic events were comparable between the two groups. The 10-year survival rate (77% vs 89%, p=0.037) and the annual adverse arrhythmic event rate (1.3% vs 0.4%, p0.01) following ASA were significantly worse in women compared with men. Kaplan-Meier analysis showed a significantly lower survival in women compared with men (p=0.023). In multivariable modelling, female sex remained independently associated with higher all-cause mortality (hazard ratio, 1.12; 95% confidence interval, 1.08-1.27; p=0.03) when adjusted for age, NYHA class III-IV symptoms, and other cardiovascular comorbidities.Female patients with HOCM undergoing ASA tended to have more severe symptoms and adverse arrhythmic events. The 10-year survival rate after ASA was significantly worse in women compared with men with HOCM. Sex may need to be considered as an important factor in the clinical management of patients with symptomatic HOCM.

Endosymbiont transmission via eggs to future host generations has been recognized as the main strategy for its persistence in insect hosts; however, the mechanisms for transmission have yet to be elucidated. Here, we describe the dynamic locations of Rickettsia in the ovarioles and eggs during oogenesis and embryogenesis in a globally significant pest whitefly Bemisia tabaci. Field populations of the whitefly have a high prevalence of Rickettsia, and in all Rickettsia-infected individuals, the bacterium distributes in the body cavity of the host, especially in the midgut, fat body, hemocytes, hemolymph, and near bacteriocytes. The distribution of Rickettsia was subjected to dynamic changes in the ovary during oogenesis, and our ultrastructural observations indicated that the bacteria infect host ovarioles during early developmental stages via two routes: (i) invasion of the tropharium by endocytosis and then transmission into vitellarium via nutritive cord and (ii) entry into vitellarium by hijacking bacteriocyte translocation. Most of the Rickettsia are degraded in the oocyte cytoplasm in late-stage oogenesis. However, a few reside beneath the vitelline envelope of mature eggs, spread into the embryo, and proliferate during embryogenesis to sustain high-fidelity transmission to the next generation. Our findings provide novel insights into the maternal transmission underpinning the persistence and spread of insect symbionts.

Yong Wang, Xiao-jiao Zhang, Hong-wei Zhao, Chengfu Wang, Defeng Luo, Qingkun Meng, Yu Zhu, Jie Tao, Baojun Chen, Yi Li, Aijie Hou, Bo Luan Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaCorrespondence: Bo Luan; Aijie HouDepartment of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, No. 33, Wenyi Road, Shenhe District, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaTel +86-17702488970Email luanbo2016@163.com; 1758624242@qq.comBackground: Retrograde microcatheter collateral channel (CC) tracking after successful wiring of septal CC is crucial for retrograde revascularization of coronary chronic total occlusion (CTO). However, the incidence, predictors, and strategies for failure of retrograde microcatheter CC tracking after successful wiring of septal CC remain unclear.Methods: In total, 298 patients with CTO who underwent retrograde septal CC PCI between January 2015 and May 2019 were retrospectively analyzed. Clinical data were compared to investigate the predictors of initial microcatheter tracking failure.Results: The initial and final microcatheter tracking success rates were 79.2% (236/298) and 96.6% (288/298), respectively. The procedural success rate was 94.0% (280/298). The right coronary artery-to-left anterior descending artery septal ratio (48.4% vs 33.1%, p=0.037) and CC tortuosity (34.6% vs 20.8%, p=0.045) were significantly higher in the initial microcatheter CC tracking failure group than in the successful tracking group. Multivariate logistic regression analysis revealed that severe collateral tortuosity (odds ratio [OR]: 13.241, 95% confidence interval [CI]: 3.429– 27.057, p=0.038), CC entry angle of < 90° (OR:4.921, 95% CI: 1.128– 9.997, p=0.002), CC exit angle of < 90° (OR:5.037, 95% CI: 2.237– 11.182, p=0.004), use of Finecross MG as initial microcatheter (OR:1.826, 95% CI: 1.127– 3.067, p=0.035), and shunning initial retrograde application of Guidezilla (OR:0.321, 95% CI: 0.267– 0.915, p=0.024) were variables independently associated with initial microcatheter CC tracking failure in patients with CTO undergoing retrograde septal CC PCI.Conclusion: The overall initial microcatheter CC tracking failure was 20.8%. Severecollateral tortuosity, CC entry, and exit angle of < 90°, use of Finecross MG as initial microcatheter, and shunning initial retrograde application of Guidezilla were variables independently associated with initial microcatheter CC tracking failure in patients with CTO undergoing retrograde septal PCI.Keywords: coronary chronic total occlusion, retrograde microcatheter tracking, collateral channel, predictor

Symbionts can regulate animal reproduction in multiple ways, but the underlying physiological and biochemical mechanisms remain largely unknown. The presence of multiple lineages of maternally inherited, intracellular symbionts (the primary and secondary symbionts) in terrestrial arthropods is widespread in nature. However, the biological, metabolic, and evolutionary role of co-resident secondary symbionts for hosts is poorly understood. The bacterial symbionts Hamiltonella and Arsenophonus have very high prevalence in two globally important pests, the whiteflies Bemisia tabaci and Trialeurodes vaporariorum, respectively. Both symbionts coexist with the primary symbiont Portiera in the same host cell (bacteriocyte) and are maternally transmitted. We found that elimination of both Hamiltonella and Arsenophonous by antibiotic treatment reduced the percentage of female offspring in whiteflies. Microsatellite genotyping and cytogenetic analysis revealed that symbiont deficiency inhibited fertilization in whiteflies, leading to more haploid males with one maternal allele, which is consistent with distorted sex ratio in whiteflies. Quantification of essential amino acids and B vitamins in whiteflies indicated that symbiont deficiency reduced B vitamin levels, and dietary B vitamin supplementation rescued fitness of whiteflies. This study, for the first time, conclusively demonstrates that these two intracellular symbionts affect sex ratios in their whitefly hosts by regulating fertilization and supplying B vitamins. Our results reveal that both symbionts have the convergent function of regulating reproduction in phylogenetically-distant whitefly species. The 100% frequency, the inability of whiteflies to develop normally without their symbiont, and rescue with B vitamins suggests that both symbionts may be better considered co-primary symbionts.

Insect symbionts are widespread in nature and lateral gene transfer is prevalent in insect symbiosis. However, the function of horizontally transferred genes (HTGs) in insect symbiosis remains speculative, including the mechanism that enables insects to feed on plant phloem deficient in B vitamins. Previously, we found there is redundancy in biotin synthesis pathways from both whitefly Bemisia tabaci and symbiotic Hamiltonella due to the presence of whitefly HTGs. Here, we demonstrate that elimination of Hamiltonella decreased biotin levels but elevated the expression of horizontally transferred biotin genes in whiteflies. HTGs proteins exhibit specific expression patterns in specialized insect cells called bacteriocytes housing symbionts. Complementation with whitefly HTGs rescued E. coli biotin gene knockout mutants. Furthermore, silencing whitefly HTGs in Hamiltonella-infected whiteflies reduced biotin levels and hindered adult survival and fecundity, which was partially rescued by biotin supplementation. Each of horizontally transferred biotin genes are conserved in various laboratory cultures and species of whiteflies with geographically diverse distributions, which shares an evolutionary origin. We provide the first experimental evidence that biotin synthesized through acquired HTGs is important in whiteflies and may be as well in other animals. Our findings suggest that B vitamin provisioning in animal-microbe symbiosis frequently evolved from bacterial symbionts to animal hosts through horizontal gene transfer events. This study will also shed light on how the animal genomes evolve through functional transfer of genes with bacterial origin in the wider contexts of microbial ecology.

Graphene is a potential candidate for applications in biomedical field. It is inevitable that graphene is in contact with the ubiquitous bacterial environment. More attention has been paid to the antimicrobial activity of graphene derivatives (graphene oxide, reduced graphene oxide) than the interaction between graphene and bacteria. Herein, we explore interaction between graphene micron-sheet and bacteria from micro (gene expression) and macro (colonies) perspectives. Results demonstrate that graphene micron-sheet accelerates the biofilm forming thus promoting pathogen expansion toward both Gram-negative bacteria E. coli and Gram-positive bacteria S. aureus. The graphene micron-sheet acts as a “habitat” for increasing bacterial attachment and biofilm forming. For E. coli, graphene micron-sheet, firstly changes the integrity of periplasmic and outer membrane components, then makes membrane-associated and cell division genes increased, and finally promotes bacterial proliferation; For S. aureus, graphene micron-sheet can accelerate biofilm forming and develop bacterial expansion owing to the regulation of the quorum-sensing system and global regulatory proteins. The work can shed new light on the range of possible mode of actions, developing a better understanding of the capabilities of graphene micron-structures.

Yong Wang, Hong-wei Zhao, Cheng-fu Wang, Xiao-jiao Zhang, Jie Tao, Chun-sheng Cui, Qing-kun Meng, Yu Zhu, De-feng Luo, Ai-jie Hou, Bo Luan Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province, 110016, People’s Republic of ChinaCorrespondence: Ai-jie Hou; Bo LuanDepartment of Cardiology, The People’s Hospital of China Medical University, the People’s Hospital of Liaoning Province, No. 33, Wenyiroad, Shenhe District, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaTel +86-17702488970Email 1758624242@qq.com; luanbo2016@163.comBackground: The incidence and prognosis of coronary slow-flow (CSF) and no-reflow phenomenon (NRP) in patients with coronary chronic total occlusion (CTO) who underwent percutaneous coronary intervention (PCI) remain unclear.Methods: This single-center prospective study aimed to investigate the incidence of CSF/NRP during CTO interventional therapy, determine predictors of CSF/NRP, and evaluate its effect on patient outcomes.Results: In this study, 552 patients with CTO who underwent PCI were included. CSF/NRP occurred in 16.1% of them. They had higher incidences of diabetes mellitus (53.9% vs 36.3%, p=0.002) and hypertension (50.6% vs 37.1%, p=0.018) and a lower incidence of retrograde filling grade > 2 (34.8% vs 47.1%, p=0.036). Patients with CSF/NRP had a higher neutrophil ratio (55.6± 19.4 vs 52.4± 18.3, p=0.038) and levels of low-density lipoprotein (LDL; 3.0± 0.8 vs 2.8± 0.6, p=0.029), fasting glucose (FG; 8.3± 1.3 vs 6.8± 1.1, p=0.005), uric acid (332.6± 82.9 vs 308.2± 62.8, p=0.045), and high-sensitivity C-reactive protein (Hs-CRP; 9.8± 4.8 vs 7.3± 3.9, p=0.036). A multivariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 1.962; 95% confidence interval [CI]: 1.198– 2.721; p=0.042), mean platelet volume (MPV; OR,1.284; 95% CI, 1.108– 1.895; p=0.046), LDL cholesterol (LDL-C; OR, 1.383; 95% CI, 1.105– 2.491; p=0.036), FG (OR, 2.095; 95% CI, 1.495– 2.899; p=0.018), Hs-CRP(OR, 2.218; 95% CI, 1.556– 3.519; p=0.029), and retrograde filling of grade > 2 (OR, 0.822; 95% CI, 0.622– 0.907; p=0.037) were independent predictors of CSF/NRP in CTO patients who underwent PCI. Kaplan-Meier analysis revealed that the patients in the CSF/NRP group had a significantly lower cumulative major cardiac and cerebrovascular events (MACCE)-free survival than those in the non-CSF/NRP group (p< 0.0001).Conclusion: Of the patients with CTO who underwent PCI, 16.1% developed CSF/NRP and had a significantly lower cumulative MACCE-free survival rate. Diabetes mellitus; higher levels of MPV, LDL-C, FG, and Hs-CRP; and a lower incidence of retrograde filling grade > 2 were independent predictors of CSF/NRP in CTO patients who underwent PCI. Thus, they can be used for risk stratification.Keywords: coronary slow-flow, no-reflow phenomenon, coronary chronic total occlusion, PCI, prognosis

There is an increasing food demand with growing population and limited land for agriculture. Conventional agriculture with nitrogen (N) fertilizer applications, however, is a key source of ammonia (NH

Background To investigate the feasibility and accuracy of the Euro CTO (CASTLE)CTA score obtained on coronary computed tomography angiography (CCTA) for predicting the success of percutaneous coronary intervention (PCI) and the 30-min wire crossing in chronic total occlusions (CTO). Method One hundred and fifty patients (154 CTO cases; median age, 61 (interquartile range [IQR], 54–68) years; 75.3% male) received CCTA at the People's Hospital of Liaoning Provincce within 1 month before the procedure. The Euro CTO (CASTLE) score obtained on CCTA(CASTLECTA) was calculated and compared with the Euro CTO (CASTLE) score obtained based on coronary angiography (CASTLECAG) for the predictive value of 30-min wire crossing and CTO procedural success. Results In our study, the CTO-PCI success rate was 89.0%, with guidewires of 65 cases (42.2%) crossing within 30 min. There were no significant differences in the median CASTLECTA and CASTLECAG scores in the procedure success group (3 [IQR, 2–4] vs 3 (IQR, 2–3]; p = 0.126). However, the median CASTLECTA score was significantly higher than the median CASTLECAG score in the procedure failure group (4 [IQR, 3–5.5] vs 4 [IQR, 2.5–5.5]; p = 0.021). There was no significant difference between the median CASTLECTA score and the median CASTLECAG score in the 30-min wire crossing failure group (3 [IQR, 3–4] vs 3 [IQR, 2–4]; p = 0.254). However, the median CASTLECTA score was significantly higher than the median CASTLECAG score in the 30-min wire crossing group (3 [IQR, 2–3] vs 2 [IQR, 2–3]; p CTA score described higher levels of calcification than the CASTLECAG score (48.1% vs 33.8%; p = 0.015). There was no significant difference between the CASTLECTA score (area under the curve [AUC], 0.643; 95% confidence interval [CI], 0.561–0.718) and the CASTLECAG score (AUC, 0.685; 95% CI, 0.606–0.758) for predicting procedural success (p = 0.488). The CASTLECTA score (AUC, 0.744; 95% CI, 0.667–0.811) was significantly better than the CASTLECAG score (AUC, 0.681; 95% CI, 0.601–0.754; p = 0.046) for predicting 30-min wire crossing with the best cut-off value being CASTLECTA ≤ 3. The sensitivity, specificity, positive predictive value, and negative predictive value were 90.8%, 55.2%, 54.6%, and 87.0%, respectively. Conclusion The CASTLECTA scores obtained from noninvasive CCTA perform better for the prediction of the 30-min wire crossing than the CASTLECAG score.

Background. Soluble growth stimulator gene 2 protein (sST2) is associated with heart failure and myocardial infarction; however, the predictive value of plasma sST2 level for coronary slow flow/no-reflow (CSF/NRF) is unclear. This study aimed to explore the predictive value of plasma sST2 levels for CSF/NRF in patients with ST-elevation myocardial infarction (STEMI) who underwent emergency percutaneous coronary intervention (PCI). Methods. A total of 242 STEMI patients who underwent emergency PCI at our hospital between November 2020 and July 2021 were enrolled in this study. According to the postprocedural procedure, these patients were divided into the CSF/NRF and control groups. Clinical data were collected from both groups and were used to explore the predictive value of serum sST2 levels for CSF/NRF. Results. Of the total 242 patients, CSF/NRF was observed in 50 patients (20.7%). Statistically significant differences ( P < 0.05 ) were observed in age, diabetes mellitus, sST2 level, neutrophil-to-lymphocyte ratio (NLR), fasting blood sugar, preprocedural blood pressure, intraprocedural hypotension, N-terminal pro-B-type natriuretic peptide, MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTNI). Multivariate analysis showed that the sST2 level, NLR, and intraoperative hypotension were independent risk factors for CSF/NRF. ROC curve analysis showed that the sensitivity and specificity of the sST2 level for predicting CSF/NRF were 68.0% and 75.5%, respectively, when the sST2 level was more than 64.6 ng/mL (AUC = 0.780, 95% CI: 1.003–1.020, P = 0.009 ). Conclusion. For STEMI patients, preprocedural sST2 levels significantly correlated with CSF/NRF occurring in PCI. sST2 level is a potential predictor for CSF/NRF occurrence.

Nutritional symbionts are restricted to specialized host cells called bacteriocytes in various insect orders. These symbionts can provide essential nutrients to the host. However, the cellular mechanisms underlying the regulation of these insect-symbiont metabolic associations remain largely unclear. The whitefly Bemisia tabaci MEAM1 hosts “Candidatus Portiera aleyrodidarum” (here, “Ca. Portiera”) and “Candidatus Hamiltonella defensa” (here, “Ca. Hamiltonella”) bacteria in the same bacteriocyte. In this study, the induction of autophagy by chemical treatment and gene silencing decreased symbiont titers and essential amino acid (EAA) and B vitamin contents. In contrast, the repression of autophagy in bacteriocytes via Atg8 silencing increased symbiont titers, and amino acid and B vitamin contents. Furthermore, dietary supplementation with non-EAAs or B vitamins alleviated autophagy in whitefly bacteriocytes, elevated TOR (target of rapamycin) expression, and increased symbiont titers. TOR silencing restored symbiont titers in whiteflies after dietary supplementation with B vitamins. These data suggest that “Ca. Portiera” and “Ca. Hamiltonella” evade autophagy of the whitefly bacteriocytes by activating the TOR pathway via providing essential nutrients. Taken together, we demonstrate that autophagy plays a critical role in regulating the metabolic interactions between the whitefly and two intracellular symbionts. Therefore, this study reveals that autophagy is an important cellular basis for bacteriocyte evolution and symbiosis persistence in whiteflies. The whitefly symbiosis unravels the interactions between cellular and metabolic functions of bacteriocytes. IMPORTANCE Nutritional symbionts, which are restricted to specialized host cells called bacteriocytes, can provide essential nutrients for many hosts. However, the cellular mechanisms of regulation of animal-symbiont metabolic associations have been largely unexplored. Here, using the whitefly-“Ca. Portiera”/“Ca. Hamiltonella” endosymbiosis, we demonstrate autophagy regulates the symbiont titers and thereby alters the essential amino acid and B vitamin contents. For persistence in the whitefly bacteriocytes, “Ca. Portiera” and “Ca. Hamiltonella” alleviate autophagy by activating the TOR (target of rapamycin) pathway through providing essential nutrients. Therefore, we demonstrate that autophagy plays a critical role in regulating the metabolic interactions between the whitefly and two intracellular symbionts. This study also provides insight into the cellular basis of bacteriocyte evolution and symbiosis persistence in the whitefly. The mechanisms underlying the role of autophagy in whitefly symbiosis could be widespread in many insect nutritional symbioses. These findings provide a new avenue for whitefly control via regulating autophagy in the future.

Chronic heart failure (CHF) seriously affects the quality of patients' lives. Sacrubitril/valsartan is a combination angiotensin receptor-neprilysin inhibitor, a new therapeutic drugs to treat CHF.This study aims to observe the impact of sacrubitril/valsartan on clinical treatment and high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-ProBNP) serum levels, the improvement of the left atrial diameter (LAD) and left ventricular end diastolic dimension (LVEDD), and the left ventricular ejection fraction (LVEF) in patients with CHF.120 patients were randomly divided into a sacrubitil/valsartan group and a valsantan group, with 60 cases in each. Patients in the sacrubitil/valsartan group were administered sacrubitril/valsartan; while in the valsantan group, they were administered valsartan. The clinical effects, adverse reactions, and rehospitalization were observed eight weeks later, and hs-cTnT and NT-ProBNP serum levels and LAD, LVEDD, and LVEF were assayed.There were 53 cases of positive effect in the sacrubitil/valsartan group and 42 in the valsartan group (P0.05). Eight participants demonstrated adverse reactions in the sacrubitil/valsartan group, while 17 in the control group (P0.05). Hs-cTnT and NT-ProBNP serum levels, the measurements of LAD, LVEDD, and LVEF in the sacrubitil/valsartan group before the treatments were (24.47 ± 7.54) pg/mL, (10,356.94 ± 5,447.68) pg/mL, (49.41 ± 5.22) mm, (68.06 ± 6.20) mm and (31.12 ±6.65) %; in the valsartan group were (29.752 ± 10.03) pg/mL, (9,518.17 ± 5,905.17) pg/mL, (49.65 ± 4.91) mm, (67.06 ± 3.97) mm, and (30.41 ± 6.11) % (P0.05), while in the sacrubitil/valsartan group, the values decreased after the treatments to (17.92 ± 4.74) pg/mL, (3,881.59 ± 2,087.79) pg/mL, (42.18 ± 4.87) mm, (60.35 ± 7.12) mm and (45.35 ± 4.49) %; in the valsartan group to (25.81 ± 7.36) pg/mL, (6,278.35 ± 2,643.11) pg/mL, (46.53 ± 4.80) mm, (64.51 ± 4.34) mm, and (36.47 ± 5.21) % (P0.05). There were significant differences within the same group, before and after treatments (P0.05).Sacrubitril/valsartan treatment of patients with CHF improves their symptoms and is deserving of clinical application. This is also evident from significantly improved levels of serum hs-cTnT and NT-ProBNP and the left ventricular function.

Objectives: In this study, we aimed to explore the influence of right-to-left shunt (RLS) presence on the clinical features of migraine and to follow-up on the post-operative curative effec...

The dramatic changes in Land-Use and Land-Cover (LULC) in urbanizing areas have led to problems such as urban flooding and water pollution. Green Stormwater Infrastructure (GSI) has become a new approach to mitigate these problems. The comprehensive assessment of GSI strategies and their combinations is the foundation for decision making regarding GSI implementation. Using the rapidly developing Western New City of Zhuhai in China as an example, this study applies Storm Water Management Model (SWMM) to evaluate Single and Combined GSI strategies. Four indicators—runoff volume control, peak flow reduction, pollutant removal, and economic cost—are selected to conduct a Multi-Criteria Decision Analysis with the use of Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). The performance evaluation of Single and Combined GSIs suggests that: (i) there may exist linear or nonlinear relation between the efficiency of a Single GSI and the size of its implementation. (ii) the optimal LULC-cost effective range may be identified for certain GSI, and (iii) Distributed-Centralized Combined GSIs are superior to other strategies in regard to reduction of runoff, TSS and peak flow. The TOPSIS assessment indicates that the cost weight ( w c ) has significant impact on the multi-criteria decision-making, and all strategies may be classified into three categories: effectiveness, cost, and stability. The results of TOPSIS show that the Distributed-Centralized Combined GSIs (scenarios S3, S5) are the best options if w c is not an important factor, while the Centralized Single GSI (S6) is the best option if w c becomes more important. Furthermore, this study can provide the well-informed alternative stormwater management plans and GSI decisions for local planners and water resource managers in the rapidly urbanizing sponge cities.

Objectives To assess the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in high-bleeding-risk elderly patients. Background Bivalirudin reduces PCI-related bleeding; however, its efficacy and safety in patients with CTO, especially elderly patients with a high bleeding risk, remain unclear. Methods This single-center prospective randomized controlled trial assigned 123 high-bleeding-risk elderly patients with CTO to either the unfractionated heparin (UFH) group (n = 55) or the bivalirudin group (n = 68). The primary efficacy endpoint was the incidence of major adverse cardiac events (MACEs) during hospitalization and at the 6-month follow-up. The safety endpoint was bleeding or procedure (access)-related complications after PCI. Results MACE incidence was 17.6% and 20.0% in the bivalirudin and UFH groups, respectively (P = 0.82). Bleeding Academic Research Consortium (BARC) type 1-2 bleeding events during hospitalization were comparable between the groups (UFH: 10.9% vs. bivalirudin: 8.8%, P = 0.77). No BARC type 3-5 bleeding events or severe procedure (access)-related complications (subcutaneous hematoma >5 cm) occurred in either group. At the 6-month follow-up, MACE incidence was comparable between the groups (UFH: 3.6% vs. bivalirudin: 1.5%, P = 0.59). The Kaplan-Meier analysis revealed that MACE-free survival rates were comparable between the groups (P = 0.43). One case of BARC type 3-5 bleeding (fatal intracranial hemorrhage) was observed in the UFH group at the 6-month follow-up. Conclusions Bivalirudin and UFH showed comparable efficacy and safety in elderly patients with a high bleeding risk, undergoing PCI for CTO lesions.

Horizontal gene transfer is widespread in insects bearing intracellular symbionts. Horizontally transferred genes (HTGs) are presumably involved in amino acid synthesis in sternorrhynchan insects. However, their role in insect-symbiont interactions remains largely unknown. We found symbionts Portiera, Hamiltonella and Rickettsia possess most genes involved in lysine synthesis in the whitefly Bemisia tabaci MEAM1 although their genomes are reduced. Hamiltonella maintains a nearly complete lysine synthesis pathway. In contrast, Portiera and Rickettsia require the complementation of whitefly HTGs for lysine synthesis and have lysE, encoding a lysine exporter. Furthermore, each horizontally transferred lysine gene of ten B. tabaci cryptic species shares an evolutionary origin. We demonstrated that Hamiltonella did not alter the titers of Portiera and Rickettsia or lysine gene expression of Portiera, Rickettsia and whiteflies. Hamiltonella also did not impact on lysine levels or protein localization in bacteriocytes harboring Portiera and ovaries infected with Rickettsia. Complementation with whitefly lysine synthesis HTGs rescued E. coli lysine gene knockout mutants. Silencing whitefly lysA in whiteflies harboring Hamiltonella reduced lysine levels, adult fecundity and titers of Portiera and Rickettsia without influencing the expression of Hamiltonella lysA. Furthermore, silencing whitefly lysA in whiteflies lacking Hamiltonella reduced lysine levels, adult fecundity and titers of Portiera and Rickettsia in ovarioles. Therefore, we, for the first time, demonstrated an essential amino acid lysine synthesized through HTGs is important for whitefly reproduction and fitness of both obligate and facultative symbionts, and it illustrates the mutual dependence between whitefly and its two symbionts. Collectively, this study reveals that acquisition of horizontally transferred lysine genes contributes to coadaptation and coevolution between B. tabaci and its symbionts., Author summary Revealing which molecules are exchanged between host and symbionts will illuminate how host and bacterial symbiont establish beneficial relationships. Horizontally transferred genes (HTGs) presumably complement the missing genes involved in synthesis of essential amino acids (EAAs) in symbionts of sternorrhynchan insects. We demonstrate that whitefly HTGs can cooperate with Portiera and Rickettsia for lysine synthesis. The lysine synthesized through HTGs impacts both whitefly reproduction and symbiont fitness. Taken together, we reveal that horizontally acquired lysine genes underlie the basis for the mutual dependence between whitefly and two intracellular symbionts. Therefore, our study demonstrates the critical role of HTGs in the synthesis of EAAs and their function in insect-symbiont interactions and coevolution.

Deep learning system (DLS) always require a time-consuming process because of too many hyperparameters and complex structure. When we update some data in DLS, a complete retraining process was encountered which spending too much time. To get over these shortcomings, the Broad Learning System (BLS) is established by C.L.Philip Chen, which aims to make a different way of artificial intelligence. By the BLS, the origin inputs are transformed and the structure of the system expanded in the feature nodes (The following is expressed as fn) and enhancement nodes (The following is expressed as en) in the wide sense. In this paper, we apply the BLS to the recognition of fake faces. Differing from previous studies, we further validate the anti-interference ability of BLS by involving a perturbation matrix P, which does not change incremental learning processes of fn and en. According to the performance on the considered dataset, BLS is more effective than DLS in recognition of fake faces. Further validation on other datasets are still necessary.

The presented 24-bit 6.4MHz sample-rate digital-to-analog converter (DAC) achieves above 130dB dynamic range in the 25 KHz band, and consumes 26.5mW with a 5-V power supply for Micro-Nano satellite systems. The digital part of the DAC includes digital interpolation filter, multi-bit MASH2-1 sigma-delta modulator, and Incremental Data Weight Average (IDWA) algorithm. The analog part of the DAC is the low-noise switched-capacitor (SC) reconstruction filter which contains only one opamp. The 128 times up-sampling hardware-efficient multistage interpolation filter based on the desensitized half-band filter's structure attains above 100dB out of band attenuation while the passband ripple is less than 0.001dB. The whole chip area is about 2.43mm2 in a 0.35µm 4-metal CMOS process. The post mixed-signal layout simulation shows that the Effective Number Of Bits (ENOB) is 22bits.

Objective: Based on differences in populations and prevention and control measures, the spread of new coronary pneumonia in different countries and regions also differs. This study aimed to calculate the transmissibility of coronavirus disease 2019 (COVID-19), and to evaluate the effectiveness of countermeasures to control the disease in Jilin Province, China.Methods: The data of reported COVID-19 cases were collected, including imported and local cases from Jilin Province as of March 14, 2019. A Susceptible–Exposed–Infectious–Asymptomatic–Recovered (SEIAR) model was developed to fit the data, and the effective reproduction number (Reff) was calculated at different stages in the province. Finally, the effectiveness of the countermeasures was assessed. Results: A total of 97 COVID-19 infections were reported in Jilin Province, among which 45 were imported infections (including one asymptomatic infection) and 52 were local infections (including three asymptomatic infections). The model fit well with the reported data (R2 = 0.593, P < 0.001). The Reff of COVID-19 before and after February 1, 2020 was 1.64 and 0.05, respectively. Without the intervention taken on February 1, 2020, the predicted cases would reach a peak of 177,011 on October 22, 2020 (284 days from the first case). The projected number of cases until the end of the outbreak (on October 9, 2021) would be 17,129,367, with a total attack rate of 63.66%. Based on the comparison between the predicted incidence of the model and the actual incidence, the comprehensive intervention measures implemented in Jilin Province on February 1 reduced the incidence of cases by 99.99%. Therefore, according to the current measures and implementation efforts, Jilin Province can achieve good control of the virus’s spread. Conclusions: COVID-19 has a moderate transmissibility in Jilin Province, China. The interventions implemented in the province had proved effective, increasing social distancing and a rapid response by the prevention and control system will help control the spread of the disease.

Objectives. To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients. Background. Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (

Some symbiotic microbes are restricted to specialized host cells called bacteriocytes. However, the molecular and cellular mechanisms underlying the development of bacteriocytes are largely obscure. We find that maternally inherited bacteriocytes proliferate in adult females but degenerate in adult males of the whitefly Bemisia tabaci. Single-cell transcriptomics and immunohistochemistry reveal that cell division only occurs in the bacteriocytes of adult females, whereas autophagy and apoptosis are induced in the bacteriocytes of adult males. A transcription factor, Adf-1, enriched in bacteriocytes, is highly expressed in female bacteriocytes relative to male bacteriocytes. Silencing Adf-1 reduces the bacteriocyte number and Portiera titer and activates autophagy and apoptosis in females. The differential dynamics of both cell division and death in bacteriocytes and distinct expression of Adf-1 in bacteriocytes between whitefly sexes underlie the sexual differentiation of bacteriocyte development. Our study reveals that insect sex affects the development of bacteriocytes by cellular and molecular remodeling.

Two new series of tricyclic heterocycles, namely 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral, free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium intermediates 14 followed by a ring-expansion rearrangement. In the rearrangement reaction, the phenyl substituent in the initially formed spiro-triazolium adducts 16 underwent a [1,2]-migration from C(3) to the electron-deficient N(2). This led to the ring expansion from 6-membered piperidine to 7-membered diazepine furnishing the tricyclic 1,2,4-triazole-fused 1,4-benzodiazepines.

The bicyclic 1-aza-2-azoniaallenium salt intermediates, generated from the azoester species upon treatment with a Lewis acid, have been demonstrated to participate in Huisgen-type cycloaddition with nitriles to result in the formation of fused 6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-d][1,4]diazepinium salts. This transformation is interpreted as a regular [3++2] cycloaddition between intermediates as the reactive 1,3-monopole reactants and nitriles as the nucleophilic reagents followed by spontaneous [1,2]-cationic rearrangement. The azoester precursors were easily accessible via oxidation of the corresponding hydrazones using hypervalent iodine oxidant PhI(OAc)2 under mild conditions. The [1,2,4]triazolodiazepine compounds represent a class of N-containing biologically important heterocycles with a new type of scaffold.

Temperature affects the persistence of diverse symbionts of insects. Our previous study indicates that the whitefly symbionts confined within bacteriocytes or scattered throughout the body cavity outside bacteriocytes may have differential thermal sensitivity. However, the underlying mechanisms remain largely unknown. Here, we report that following continuous heat stress, Portiera and Hamiltonella were almost completely depleted in two species of Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED) of the Bemisia tabaci whitefly cryptic species complex. Meanwhile, proliferation of bacteriocytes was severely inhibited and approximately 50% of the nymphs had lost one of the two bacteriomes. While cell size of bacteriocytes was increased, cell number was severely decreased leading to reduction of total volume of bacteriocytes. Moreover, bacteriocyte organelles and associated symbionts were lysed, and huge amount of electron-dense inclusions accumulated. Eventually, Portiera and Hamiltonella failed to be transmitted to the next generation. In contrast, Rickettsia could be detected although at a reduced level, and successfully transmitted to eggs. The results suggest that the thermal sensitivity of bacteriocytes may limit thermal tolerance and vertical transmission of the associated symbionts, and consequently different patterns of distribution of symbionts may affect their capacity to tolerate unfavourable temperatures and persistence in the host.

In recent years, with the emergence of high-computing GPUs and the introduction of new convolutional neural network models, deep learning technology has ushered in a new round of development. At the same time, in the era of rapid development of the Internet, a large amount of high-quality medical image data is generated every day, which provides a new opportunity for the deep learning to develop in the field of automatic analysis and auxiliary diagnosis of medical images. In this paper, R-FCN (region-based fully convolutional networks) are introduced into the lesion detection of the larynx, and the classification result of the lesion can be given while confirming the lesion area. In view of the existing image-based classification, there can only be one organ in the image and the background must be simple. Through the target detection method, multi-organ target can be realized and detected under complex background. The experimental results show that the target in complex scenes can be effectively identified when the training data is sufficient.

Background Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear. Method We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI. Results The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan–Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group. Conclusion In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.

Whiteflies possess bacterial symbionts Candidatus Portiera aleyrodidium that are housed in specialized cells called bacteriocytes and are faithfully transmitted via the ovary to insect offspring. In one whitefly species studied previously, Bemisia tabaci MEAM1, transmission is mediated by somatic inheritance of bacteriocytes, with a single bacteriocyte transferred to each oocyte and persisting through embryogenesis to the next generation. Here, we investigate the mode of bacteriocyte transmission in two whitefly species, B. tabaci MED, the sister species of MEAM1, and the phylogenetically distant species Trialeurodes vaporariorum. Microsatellite analysis supported by microscopical studies demonstrates that B. tabaci MED bacteriocytes are genetically different from other somatic cells and persist through embryogenesis, as for MEAM1, but T. vaporariorum bacteriocytes are genetically identical to other somatic cells of the insect, likely mediated by the degradation of maternal bacteriocytes in the embryo. These two alternative modes of transmission provide a first demonstration among insect symbioses that the cellular processes underlying vertical transmission of bacterial symbionts can diversify among related host species associated with a single lineage of symbiotic bacteria.

The high osmotic pressure generated by sugars in plant phloem sap is reduced in phloem-feeding aphids by sugar transformations and facilitated water flux in the gut. The genes mediating these osmoregulatory functions have been identified and validated empirically in the pea aphid Acyrthosiphon pisum: sucrase 1 (SUC1), a sucrase in glycoside hydrolase family 13 (GH13), and aquaporin 1 (AQP1), a member of the Drosophila integral protein (DRIP) family of aquaporins. Here, we describe molecular analysis of GH13 and AQP genes in phloem-feeding representatives of the four phloem-feeding groups: aphids (Myzus persicae), coccids (Planococcus citri), psyllids (Diaphorina citri, Bactericera cockerelli) and whiteflies (Bemisia tabaci MEAM1 and MED). A single candidate GH13-SUC gene and DRIP-AQP gene were identified in the genome/transcriptome of most insects tested by the criteria of sequence motif and gene expression in the gut. Exceptionally, the psyllid Ba. cockerelli transcriptome included a gut-expressed Pyrocoelia rufa integral protein (PRIP)-AQP, but has no DRIP-AQP transcripts, suggesting that PRIP-AQP is recruited for osmoregulatory function in this insect. This study indicates that phylogenetically related SUC and AQP genes may generally mediate osmoregulatory functions in these diverse phloem-feeding insects, and provides candidate genes for empirical validation and development as targets for osmotic disruption of pest species.

Two new series of tricyclic heterocycles, namely 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral, free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium intermediates 14 followed by a ring-expansion rearrangement. In the rearrangement reaction, the phenyl substituent in the initially formed spiro-triazolium adducts 16 underwent a [1,2]-migration from C(3) to the electron-deficient N(2). This led to the ring expansion from 6-membered piperidine to 7-membered diazepine furnishing the tricyclic 1,2,4-triazole-fused 1,4-benzodiazepines.

Fresh water is consumed during agricultural production. With the shortage of water resources, assessing the water use efficiency is crucial to effectively managing agricultural water resources. The water footprint is a new index for water use evaluation, and it can reflect the quantity and types of water usage during crop growth. This study aims to establish a method for calculating the region-scale water footprint of crop production based on hydrological processes. This method analyzes the water-use process during the growth of crops, which includes irrigation, precipitation, underground water, evapotranspiration, and drainage, and it ensures a more credible evaluation of water use. As illustrated by the case of the Hetao irrigation district (HID), China, the water footprints of wheat, corn and sunflower were calculated using this method. The results show that canal water loss and evapotranspiration were responsible for most of the water consumption and accounted for 47.9 % and 41.8 % of the total consumption, respectively. The total water footprints of wheat, sunflower and corn were 1380–2888 m3/t, 942–1774 m3/t, and 2095–4855 m3/t, respectively, and the blue footprint accounts for more than 86 %. The spatial distribution pattern of the green, blue and total water footprint for the three crops demonstrated that higher values occurred in the eastern part of the HID, which had more precipitation and was further from the irrigating gate. This study offers a vital reference for improving the method used to calculate the crop water footprint.

The bicyclic 1-aza-2-azoniaallenium salt intermediates, generated from the azoester species upon treatment with a Lewis acid, have been demonstrated to participate in Huisgen-type cycloaddition with nitriles to result in the formation of fused 6,7,8,9-tetrahydro-5 H-[1,2,4]triazolo[1,5- d][1,4]diazepinium salts. This transformation is interpreted as a regular [3