bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Detection of mecA-Mediated β-Lactam Resistance in Staphylococcus lugdunensis Using a New Oxacillin Salt Agar Screen
Authors: Ho Pak-Leung , Law Ying-Hang , Liu Melissa Chun-Jiao , Lau Andes , Tong Man-Ki , Chow Kin-Hung , Wu Alan Ka-Lun , Tse Cindy Wing-Sze , Cheng Vincent Chi-Chung , Que Tak-Lun
Published: August 2021

Oxacillin resistance mediated bymecAinStaphylococcus lugdunensisis emerging in some geographic areas. We evaluated cefoxitin disk diffusion (DD) and a new oxacillin agar (supplemented with 2 μg/ml oxacillin and 2% sodium chloride) screen for the detection ofmecA-mediated resistance inS. lugdunensis. A total of 300 consecutive, non-duplicated clinicalS. lugdunensisisolates from diverse sources in Hong Kong in 2019 were tested. The categorical agreement and errors obtained between cefoxitin DD test, oxacillin agar screen andmecAPCR were analyzed. Isolates with discordant results were further tested by MIC, penicillin binding protein 2a (PBP2a) assays, population analysis and molecular typing. PCR showed that 62 isolates weremecA-positive and 238 isolates weremecA-negative. For cefoxitin DD results interpreted usingS. aureus/S. lugdunensisbreakpoints, the categorical agreement (CA) for two brands of Muller-Hinton agars, MH-II (Becton Dickinson) and MH-E (bioMérieux) were both 96.0%; MEs were both 0%; and VMEs were 19.4 and 12.9%, respectively. The new oxacillin agar reliably differentiatedmecA-positive andmecA-negative isolates (100% CA) without any ME or VME results. The 8 isolates with false susceptibility in the cefoxitin DD testing had cefoxitin and oxacillin MICs in the susceptible range. The isolates showed heterogeneous oxacillin resistance with resistant subpopulations at low frequencies. All had positive PBP2a results and were typed as sequence type 27/SCCmecV. The findings highlight the inability of cefoxitin DD and MIC tests for reliable detection of somemecA-positiveS. lugdunensisisolates.
Electron Transfer Coupled to Conformational Dynamics in Cell Respiration
Authors: Reidelbach Marco , Zimmer Christoph , Meunier Brigitte , Rich Peter R. , Sharma Vivek
Published: August 2021

Cellular respiration is a fundamental process required for energy production in many organisms. The terminal electron transfer complex in mitochondrial and many bacterial respiratory chains is cytochrome c oxidase (CcO). This converts the energy released in the cytochrome c/oxygen redox reaction into a transmembrane proton electrochemical gradient that is used subsequently to power ATP synthesis. Despite detailed knowledge of electron and proton transfer paths, a central question remains as to whether the coupling between electron and proton transfer in mammalian mitochondrial forms of CcO is mechanistically equivalent to its bacterial counterparts. Here, we focus on the conserved span between H376 and G384 of transmembrane helix (TMH) X of subunit I. This conformationally-dynamic section has been suggested to link the redox activity with the putative H pathway of proton transfer in mammalian CcO. The two helix X mutants, Val380Met (V380M) and Gly384Asp (G384D), generated in the genetically-tractable yeast CcO, resulted in a respiratory-deficient phenotype caused by the inhibition of intra-protein electron transfer and CcO turnover. Molecular aspects of these variants were studied by long timescale atomistic molecular dynamics simulations performed on wild-type and mutant bovine and yeast CcOs. We identified redox- and mutation-state dependent conformational changes in this span of TMH X of bovine and yeast CcOs which strongly suggests that this dynamic module plays a key role in optimizing intra-protein electron transfers.
Nocturnal Sleep Problems Mediate the Impact on Quality of Life of Early Morning Off in Parkinson's Disease
Authors: Zhang Yu , Zhang Zi en , Shi De , Zhao Yi , Huang Lihong , Zhao Yanxin , Wang Hui , Zhao Jing , Wang Feng , Zhao Chaorong , Gao Shan , Wei Wenshi , Huang Dongya , Liu Zhen guo
Published: August 2021

Background: Early morning off (EMO) refers to off-states in the morning in people diagnosed with Parkinson's disease (PwPD). This study determined the clinical manifestations of EMO and the association with nocturnal sleep problems and quality of life (QOL) in Chinese PwPD.

Methods: In this multicenter, observational, cross-sectional study, data concerning the clinical manifestations of EMO were collected from PwPD in Shanghai by questionnaire. The stepwise logistic regression was performed to analyze the potential risk factors, as well as whether EMO was an independent risk factor for functional dependency in daily life. The mediation analyses were conducted to evaluate whether nocturnal sleep problems might mediate the association between EMO and the QOL.

Results: Among the 454 subjects evaluated, EMO occurred in 39.43% of PwPD across all disease stages. The prevalence of EMO increased as the Hoehn and Yahr stage increased and was observed in 35.60% of patients in stages 1–2.5 and 48.85% of patients in stages 3–5. EMO was associated with non-motor symptoms (NMSs). The predominant NMSs associated with EMO were nocturnal sleep problems (98.90%), mood/cognition impairment (93.90%), decreased attention/memory (91.60%), gastrointestinal symptoms (91.60%), and urinary urgency (90.50%). The QOL of PwPD with EMO was significantly reduced (P < 0.001). Moreover, nocturnal sleep problems might partially mediate this relationship (indirect effect: β = 13.458, 95% boot CI: 6.436, 22.042).

Conclusion: PwPD have EMO throughout all stages of the disease. Patients with EMO have severe motor symptoms and NMSs. EMO decreases the QOL in PwPD and this relationship is partially mediated by nocturnal sleep problems. In light of these findings, it is suggested that recognition and appropriate treatment of EMO and nocturnal sleep problems could improve the management of PwPD.
Tenecteplase Thrombolysis in Posterior Circulation Stroke
Authors: Alemseged Fana , Campbell Bruce C. V.
Published: August 2021

One in five ischaemic strokes affects the posterior circulation. Basilar artery occlusion is a type of posterior circulation stroke associated with a high risk of disability and mortality. Despite its proven efficacy in ischaemic stroke more generally, alteplase only achieves rapid reperfusion in ~4% of basilar artery occlusion patients. Tenecteplase is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, which can be administered by intravenous bolus. The single-bolus administration of tenecteplase vs. an hour-long alteplase infusion is a major practical advantage, particularly in “drip and ship” patients with basilar artery occlusion who are being transported between hospitals. Other practical advantages include its reduced cost compared to alteplase. The EXTEND-IA TNK trial demonstrated that tenecteplase led to higher reperfusion rates prior to endovascular therapy (22 vs. 10%, non-inferiority p = 0.002, superiority p = 0.03) and improved functional outcomes (ordinal analysis of the modified Rankin Scale, common odds ratio 1.7, 95% CI 1.0–2.8, p = 0.04) compared with alteplase in large-vessel occlusion ischaemic strokes. We recently demonstrated in observational data that tenecteplase was associated with increased reperfusion rates compared to alteplase prior to endovascular therapy in basilar artery occlusion [26% (n = 5/19) of patients thrombolysed with TNK vs. 7% (n = 6/91) thrombolysed with alteplase (RR 4.0 95% CI 1.3–12; p = 0.02)]. Although randomized controlled trials are needed to confirm these results, tenecteplase can be considered as an alternative to alteplase in patients with basilar artery occlusion, particularly in “drip and ship” patients.
Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease
Authors: Aquino Camila Henriques de
Published: August 2021

Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative disorders, respectively. Both are proteinopathies with inexorable courses and no approved disease-modifying therapies. A substantial effort has been made to identify interventions that could slow down the progression of AD and PD; to date, with no success. The advances in biomarker research improved the identification of individuals at risk for these disorders before symptom onset, recognizing the pre-clinical stage, in which there is abnormal protein accumulation but no clinical symptoms of the disease, and the prodromal stage, in which mild symptoms are present but the clinical diagnostic criteria for disease cannot be fulfilled. The ability to detect pre-clinical and prodromal stages of these diseases has encouraged clinical trials for disease-modification at earlier phases, seeking to slow or prevent phenoconversion into clinical disease. Clinical trials at these stages have several challenges, such as the identification of the eligible population, the appropriate choice of biomarkers, the definition of clinical endpoints, the duration of follow-up, and the statistical analysis. This article aims to discuss some of the methodological challenges in the design of trials for pre-clinical and prodromal phases of AD and PD, to critically review the recent studies, and to discuss methodological approaches to mitigate these challenges in trial design.
Advances in Neural Recording and Stimulation Integrated Circuits
Authors: Li Juzhe , Liu Xu , Mao Wei , Chen Tao , Yu Hao
Published: August 2021

In the past few decades, driven by the increasing demands in the biomedical field aiming to cure neurological diseases and improve the quality of daily lives of the patients, researchers began to take advantage of the semiconductor technology to develop miniaturized and power-efficient chips for implantable applications. The emergence of the integrated circuits for neural prosthesis improves the treatment process of epilepsy, hearing loss, retinal damage, and other neurological diseases, which brings benefits to many patients. However, considering the safety and accuracy in the neural prosthesis process, there are many research directions. In the process of chip design, designers need to carefully analyze various parameters, and investigate different design techniques. This article presents the advances in neural recording and stimulation integrated circuits, including (1) a brief introduction of the basics of neural prosthesis circuits and the repair process in the bionic neural link, (2) a systematic introduction of the basic architecture and the latest technology of neural recording and stimulation integrated circuits, (3) a summary of the key issues of neural recording and stimulation integrated circuits, and (4) a discussion about the considerations of neural recording and stimulation circuit architecture selection and a discussion of future trends. The overview would help the designers to understand the latest performances in many aspects and to meet the design requirements better.
From the Wild to the Cup: Tracking Footprints of the Tea Species in Time and Space
Authors: Wambulwa Moses C. , Meegahakumbura Muditha K. , Kamunya Samson , Wachira Francis N.
Published: August 2021

Tea is one of the world's most popular beverages, known for its cultural significance and numerous health benefits. A clear understanding of the origin and history of domestication of the tea species is a fundamental pre-requisite for effective germplasm conservation and improvement. Though there is a general consensus about the center of origin of the tea plant, the evolutionary origin and expansion history of the species remain shrouded in controversy, with studies often reporting conflicting findings. This mini review provides a concise summary of the current state of knowledge regarding the origin, domestication, and dissemination of the species around the world. We note that tea was domesticated around 3000 B.C. either from non-tea wild relatives (probably Camellia grandibracteata and/or C. leptophylla) or intra-specifically from the wild Camellia sinensis var. assamica trees, and that the genetic origins of the various tea varieties may need further inquiry. Moreover, we found that lineage divergence within the tea family was apparently largely driven by a combination of orogenic, climatic, and human-related forces, a fact that could have important implications for conservation of the contemporary tea germplasm. Finally, we demonstrate the robustness of an integrative approach involving linguistics, historical records, and genetics to identify the center of origin of the tea species, and to infer its history of expansion. Throughout the review, we identify areas of debate, and highlight potential research gaps, which lay a foundation for future explorations of the topic.
Radiomics Study for Predicting the Expression of PD-L1 and Tumor Mutation Burden in Non-Small Cell Lung Cancer Based on CT Images and Clinicopathological Features
Authors: Wen Qiang , Yang Zhe , Dai Honghai , Feng Alei , Li Qiang
Published: August 2021

Background

The present study compared the predictive performance of pretreatment computed tomography (CT)-based radiomics signatures and clinicopathological and CT morphological factors for ligand programmed death-ligand 1 (PD-L1) expression level and tumor mutation burden (TMB) status and further explored predictive models in patients with advanced-stage non-small cell lung cancer (NSCLC).

Methods

A total of 120 patients with advanced-stage NSCLC were enrolled in this retrospective study and randomly assigned to a training dataset or validation dataset. Here, 462 radiomics features were extracted from region-of-interest (ROI) segmentation based on pretreatment CT images. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to select radiomics features and develop combined models with clinical and morphological factors for PD-L1 expression and TMB status prediction. Ten-fold cross-validation was used to evaluate the accuracy, and the predictive performance of these models was assessed using receiver operating characteristic (ROC) and area under the curve (AUC) analyses.

Results

The PD-L1-positive expression level correlated with differentiation degree (p = 0.005), tumor shape (p = 0.006), and vascular convergence (p = 0.007). Stage (p = 0.023), differentiation degree (p = 0.017), and vacuole sign (p = 0.016) were associated with TMB status. Radiomics signatures showed good performance for predicting PD-L1 and TMB with AUCs of 0.730 and 0.759, respectively. Predictive models that combined radiomics signatures with clinical and morphological factors dramatically improved the predictive efficacy for PD-L1 (AUC = 0.839) and TMB (p = 0.818). The results were verified in the validation datasets.

Conclusions

Quantitative CT-based radiomics features have potential value in the classification of PD-L1 expression levels and TMB status. The combined model further improved the predictive performance and provided sufficient information for the guiding of immunotherapy in clinical practice, and it deserves further analysis.
Development of a Quantitative Diagnostic Criterion for Gastric Linitis Plastica: Findings From a Large Single-Institutional Study
Authors: Han Yang , Xuan Yi , Liu Xiaowen , Zhu Hui , Zhang Meng , Xu Dazhi , Wang Yanong , Cai Hong
Published: August 2021

Gastric linitis plastica (GLP) is a descriptive term but lacks a quantitative definition. Several relatively quantitative criteria had been proposed, such as tumor involving a limit of one-third or two-thirds of the gastric surface. However, these criteria needed doctors to subjectively judge tumor infiltration area, which made diagnosis difficult to be objective and reproducible. This study aimed to propose a quantitative diagnostic criterion for distinguishing GLP. We performed a retrospective cohort study of 2,907 patients with Borrmann III and IV gastric cancer (GC) who underwent gastrectomy between 2011 and 2018 in our center. The Kaplan–Meier curves showed that patients with an observed tumor size more than 8 cm had obviously lower overall survival (OS) and disease-free survival (DFS) rates than those with a size less than 8 cm(p < 0.001; p < 0.001). However, there was no significantly different prognosis of patients with tumor sizes between more than 8 cm and more than 10 cm (p = 0.248; p = 0.534). Moreover, patients with tumor sizes greater than 8 cm more presented with advanced stage and had extremely poor 3-year OS and DFS (31.4%; 29.3%), with a stronger propensity toward peritoneal metastasis. Therefore, we considered patients’ observed tumor size more than 8 cm as a critical value for distinguishing the prognosis of Borrmann III and IV GC. Furthermore, we proposed an observed tumor size more than 8 cm as a quantitative diagnostic criterion for GLP on the premise of satisfying the originally descriptive and pathological definition regardless of Borrmann type.
Safety and Efficacy of Laparoscopic Versus Open Gastrectomy in Patients With Advanced Gastric Cancer Following Neoadjuvant Chemotherapy: A Meta-Analysis
Authors: Liao Xu-Liang , Liang Xian-Wen , Pang Hua-Yang , Yang Kun , Chen Xin-Zu , Chen Xiao-Long , Liu Kai , Zhao Lin-Yong , Zhang Wei-Han , Hu Jian-Kun
Published: August 2021

Background

Given the expanding clinical applications of laparoscopic surgery and neoadjuvant chemotherapy in advanced gastric cancer treatment, there is an emerging need to summarize the few evidences that evaluated the safety and efficacy of laparoscopic versus open gastrectomy in patients with advanced gastric cancer (AGC) following neoadjuvant chemotherapy (NAC).

Methods

From January 1 to 2, 2021, we searched Ovid Embase, PubMed, Cochrane central register Trials (Ovid), and web of science to find relevant studies published in English, and two authors independently performed literature screening, quality assessment of the included studies, data extraction, and data analysis. This study was registered with PROSPERO (CRD42021228845).

Results

The initial search retrieved 1567 articles, and 6 studies were finally included in the meta-analysis review, which comprised 2 randomized control trials and 4 observational studies involving 288 laparoscopic gastrectomy (LG) and 416 open gastrectomy (OG) AGC patients treated with NAC. For intraoperative conditions, R0 resection rate, blood transfusion, intraoperative blood loss, number of lymph nodes dissected, proximal margin, and distal margin were comparable between LG group and open OG group. For postoperative short-term clinical outcomes, LG has significantly less postoperative complications (OR = 0.65, 95%CI: 0.42–1.00, p = 0.05) and shorter postoperative time to first aerofluxus (WMD = -0.57d, 95%CI: -0.89–0.25, p = 0.0004) than OG, and anastomotic leakage, pulmonary infection, pleural effusion, surgical site infection, thrombosis, intestinal obstruction, peritoneal effusion or abscess formation, postoperative time to first defecation, postoperative time to first liquid diet, and postoperative length of stay were comparable between the two groups. For postoperative survival outcomes, there were no significant differences in disease-free survival (DFS) and overall survival (OS) between the two groups.

Conclusion

The available evidences indicated that LG is an effective and feasible technology for the treatment of AGC patients treated with NAC, and LG patients have much less postoperative complications and faster bowel function recovery than OG patients.

Systematic Review Registration

PROSPERO database (identifier, CRD42021228845).
Tryptophan and Its Metabolites in Lung Cancer: Basic Functions and Clinical Significance
Authors: Li Chenwei , Zhao Hui
Published: August 2021

Lung cancer is the most lethal malignancy worldwide. Recently, it has been recognized that metabolic reprogramming is a complex and multifaceted factor, contributing to the process of lung cancer. Tryptophan (Try) is an essential amino acid, and Try and its metabolites can regulate the progression of lung cancer. Here, we review the pleiotropic functions of the Try metabolic pathway, its metabolites, and key enzymes in the pathogenic process of lung cancer, including modulating the tumor environment, promoting immune suppression, and drug resistance. We summarize the recent advance in therapeutic drugs targeting the Try metabolism and kynurenine pathway and their clinical trials.
ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2
Authors: Zhuang Qiu-Shi , Sun Xin-Bao , Chong Qing-Yun , Banerjee Arindam , Zhang Min , Wu Zheng-Sheng , Zhu Tao , Pandey Vijay , Lobie Peter E.
Published: August 2021

ARTEMIN (ARTN), one of the glial-cell derived neurotrophic factor family of ligands, has been reported to be associated with a number of human malignancies. In this study, the enhanced expression of ARTN in colorectal carcinoma (CRC) was observed; the expression of ARTN positively correlated with lymph node metastases and advanced tumor stages and predicted poor prognosis. Forced expression of ARTN in CRC cells enhanced oncogenic behavior, mesenchymal phenotype, stem cell-like properties and tumor growth and metastasis in a xenograft model. These functions were conversely inhibited by depletion of endogenous ARTN. Forced expression of ARTN reduced the sensitivity of CRC cells to 5-FU treatment; and 5-FU resistant CRC cells harbored enhanced expression of ARTN. The oncogenic functions of ARTN were demonstrated to be mediated by p44/42 MAP kinase dependent expression of CDH2 (CADHERIN 2, also known as N-CADHERIN). Inhibition of p44/42 MAP kinase activity or siRNA mediated depletion of endogenous CDH2 reduced the enhanced oncogenicity and chemoresistance consequent to forced expression of ARTN induced cell functions; and forced expression of CDH2 rescued the reduced mesenchymal properties and resistance to 5-FU after ARTN depletion. In conclusion, ARTN may be of prognostic and theranostic utility in CRC.
Case Report: Dilated Cardiomyopathy in a Newborn, a Potential Association With SARS-COV-2
Authors: Azeka Estela , Arshad Adam , Martins Cristiane , Dominguez Anna Claudia , Siqueira Adailson , Loss Andre Silveira , Jatene Marcelo , Miura Nana
Published: August 2021

Objective: The objective of this study was to describe the clinical course of a newborn who developed dilated cardiomyopathy (DCM) after COVID-19 infection.

Methods: We retrospectively assessed the clinical notes of a pediatric patient with decompensated heart failure and who was previously positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results: A 23-day-old newborn presented with diarrhea, hypoactivity, tachypnea, and lethargy. The infant progressed to develop respiratory failure and required orotracheal intubation due to apnea. A nasopharyngeal swab tested positive for SARS-COV-2. An echocardiogram (ECHO) demonstrated severe left ventricular dysfunction. The patient was discharged after 18 days with furosemide and angiotensin-converting enzyme inhibitors. During the follow-up period, the infant had two episodes of decompensated heart failure, with evidence of DCM. Investigations for known causes of secondary DCM were negative. The infant was promptly referred for heart transplantation.

Conclusion: Although rare, we have observed a case of DCM in a newborn following COVID-19 disease. DCM may be a complication following COVID-19 disease in newborns.
Case Report: Mitral Valve Involvement and First-Degree Atrial-Ventricular Block in Two Patients With Multisystem Inflammatory Syndrome in Children
Authors: Di Filippo Paola , Raso Massimiliano , Cacciatore Marta , Patacchiola Roberta , Renda Giulia , Rossi Nadia , Chiarelli Francesco
Published: August 2021

COVID-19 seems to be less frequent and severe in children compared to adults. Despite the very few symptoms usually found in children, great attention was recorded when in April 2020 a hyperinflammatory process in children with fever and multiorgan involvement after a paucisymptomatic COVID infection was reported. The United States Centers for Disease Control and the World Health Organization recognized and defined this syndrome as “Multisystem Inflammatory Syndrome in Children (MIS-C).” We describe two cases of MIS-C presenting with fever, cutaneous rash, and a mild cardiac involvement expressed with a transient mitral valve involvement and a first-degree atrioventricular block. Acute treatment was managed with intravenous immunoglobulin, oral aspirin, and intravenous corticosteroids reaching consequent good outcome. Clinical characteristics, treatment management, follow-up, and long-term evolution of children with MIS-C are still poorly defined. Further research is needed to better understand the pathogenesis of this newly described condition, to validate a high-level recommended therapy and a specific therapy tapering timings.
Agmatine Alleviates Epileptic Seizures and Hippocampal Neuronal Damage by Inhibiting Gasdermin D-Mediated Pyroptosis
Authors: Li Xueying , Lin Jiahe , Hua Yingjie , Gong Jiaoni , Ding Siqi , Du Yanru , Wang Xinshi , Zheng Rongyuan , Xu Huiqin
Published: August 2021

Background: Epilepsy is a common neurological disease, and neuroinflammation is one of the main contributors to epileptogenesis. Pyroptosis is a type of pro-inflammatory cell death that is related to epilepsy. Agmatine, has anti-inflammatory properties and exerts neuroprotective effects against seizures. Our study investigated the effect of agmatine on the core pyroptosis protein GSDMD in the context of epilepsy.

Methods: A chronic epilepsy model and BV2 microglial cellular inflammation model were established by pentylenetetrazole (PTZ)-induced kindling or lipopolysaccharide (LPS) stimulation. H&E and Nissl staining were used to evaluate hippocampal neuronal damage. The expression of pyroptosis and inflammasome factors was examined by western blotting, quantitative real-time PCR, immunofluorescence and enzyme-linked immunosorbent assay (ELISA).

Results: Agmatine disrupted the kindling acquisition process, which decreased seizure scores and the incidence of full kindling and blocked hippocampal neuronal damage. In addition, agmatine increased BV2 microglial cell survival in vitro and alleviated seizures in vivo by suppressing the levels of PTZ-induced pyroptosis. Finally, the expression of TLR4, MYD88, phospho-IκBα, phospho-NF-κB and the NLRP3 inflammasome was significantly upregulated in LPS-induced BV2 microglial cells, while agmatine suppressed the expression of these proteins.

Conclusions: Our results indicate that agmatine affects epileptogenesis and exerts neuroprotective effects by inhibiting neuroinflammation, GSDMD activation, and pyroptosis. The inhibitory effect of agmatine on pyroptosis was mediated by the suppression of the TLR4/MYD88/NF-κB/NLRP3 inflammasome pathway. Therefore, agmatine may be a potential treatment option for epilepsy.
Macleayins A From Macleaya Promotes Cell Apoptosis Through Wnt/β-Catenin Signaling Pathway and Inhibits Proliferation, Migration, and Invasion in Cervical Cancer HeLa Cells
Authors: Sai Chunmei , Qin Wei , Meng Junyu , Gao Li-Na , Huang Lufen , Zhang Zhen , Wang Huannan , Chen Haixia , Yan Chaohua
Published: August 2021

Macleayins A (MA), a novel compound, was isolated from Macleaya cordata (Willd.) R. Br. and Macleaya microcarpa (Maxim.) Fedde. The plant species are the member of Papaveraceae family and have been used traditionally for diverse therapeutic purposes. According to the reported studies, the chemical constituents, as well as crude extracts of these plants, could attenuate the proliferation of several cancer cell lines, such as HL-60, A549, HepG2, and MCF-7. The current study aimed to investigate the anticervical cancer activity of MA and its related molecular mechanism. Isolation of MA was carried out using various column chromatographic methods, and its structure was elucidated with 1H NMR. The cytotoxicity of MA was determined against HeLa cell lines via CCK-8 assay. The cell proliferation, apoptosis, cell cycle, migration, and invasion were measured by EdU labeling, Annexin-V APC/7-AAD double staining, PI staining, and transwell assay, respectively. The protein expression levels of c-Myc, β-catenin, cyclin D1, and MMP-7 in the cells were evaluated by western blotting. The Wnt/β-catenin signaling cascade activation was verified using the Dual-Glo® Luciferase assay. We found that MA inhibited the growth of HeLa cells at 72 h (IC50 = 26.88 µM) via inducing apoptotic process, reduced the proliferation rate by 29.89%, and decreased the cells migration and invasion as compared to the untreated group. It arrested the cell cycle at the G1 phase and its treatment inhibited the expression of related proteins c-Myc, β-catenin, cyclin D1, and MMP-7 in the Wnt/β-catenin signaling cascade. Further, the Wnt/β-catenin signaling cascade activation in MA-treated HeLa cells was attenuated in a dose-dependent manner. These findings demonstrate the anticancer effects of MA on a mechanistic level, thus providing a basis for MA to become a potential candidate drug for resistance of cervical carcinoma.
Efficacy and Safety of Chinese Patent Medicine Combined With Oseltamivir in Treatment of Children With Influenza: A meta-Analysis
Authors: Duan Nai-fan , Liu Bin , Li Xiao-na , Xiong Yi-bai , Zhang Yan , Zhang Chi , LI Li , Lu Cheng , Lyu Jueni
Published: August 2021

Background: Recently, Chinese patent medicines (CPMs) have been widely used to treat children with influenza in China, with curative effects. Therefore, the efficacy and safety of such treatment require further evaluation. The present meta-analysis integrated data from several independent studies to determine overall treatment trends in children with influenza.

Methods: The following databases were searched for randomized controlled trials (RCTs) published from their inception to December 12, 2020: CNKI, Wanfang, SinoMed, PubMed, Cochrane library, and Embase. Two researchers independently extracted the data, assessed the methodological quality of the studies, and conducted a meta-analysis of the results using Review Manager 5.2. The results were assessed using forest plots, and publication bias was evaluated using a funnel plot.

Results: A total of 21 RCTs involving 2960 cases were included. Compared to oseltamivir alone, CPMs combined with oseltamivir reduced the duration of symptoms, including that of fever (mean difference [MD] = −0.64, 95% confidence interval [CI]: −0.86 to −0.41, P < 0.00001), cough (MD = −0.82, 95% CI: −1.02 to −0.62, P < 0.00001), nasal obstruction (MD = −0.88, 95% CI: −1.15 to −0.61, P < 0.00001), and sore throat (MD = −0.92, 95% CI: −1.26 to −0.57, P < 0.00001). Combined therapy also reduced the time of viral shedding (MD = −0.53, 95% CI: −0.70 to −0.36, P < 0.00001) and the occurrence of adverse drug reactions (ADRs) (RR=0.53, 95% CI: 0.34 to 0.83, P = 0.005).

Conclusions: CPMs combined with oseltamivir reduced the duration of symptoms, shortened the time of viral shedding, and reduced the number of ADRs. However, these results should be considered with caution because there was marked heterogeneity and publication bias in the research data. More rigorous RCTs should be designed to verify the effect of CPMs in children with influenza.
Greater than the Sum: Applying Daily-Dose Equivalents to Antipsychotic Prescription Claims to Study Real-World Effects
Authors: Hayes Kaleen N. , Gomes Tara , Tadrous Mina
Published: August 2021

Traditional methods to standardize exposures in pharmacoepidemiologic studies, like defined daily-doses, may be inadequate to capture drug class effects when there are many in-class medications, formulations, and administration routes. Antipsychotic medications are one example of a drug class with these complexities. Direct dose conversion methods are pharmacologically-based but often overlooked, potentially for lack of real-world guidance and examples of their implementation. The purpose of this article is to describe a method to implement dose conversion, using an example study that quantifies antipsychotic use among a cohort of older adults with dementia. We identified 45,442 older adults (aged ≥66 years) with dementia initiating antipsychotic therapy between January 1, 2009 and December 31, 2012 in Ontario, Canada using linked administrative healthcare databases. We developed and applied a data cleaning and dose conversion algorithm to quantify antipsychotic exposure in chlorpromazine dose equivalents at initiation, month 6, and month 12 of therapy. Results were stratified by route of administration. At initiation, 14% of patients received multiple antipsychotic prescriptions simultaneously. Patients initiating regular injectable and multiple administration routes received the highest median chlorpromazine equivalent daily-doses. Data cleaning changed 3, 16, 36, and 42% of total equivalent daily-doses in patients initiating oral, regular injectable, long-acting injectable, and multiple administration routes, respectively. Dose conversion of prescription claims data was a feasible method to quantify and present antipsychotic drug exposures. Dose conversion methods can be considered for drug effects studies of antipsychotic therapies and other medication classes with complex use.
Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells
Authors: Chen Chao-Jung , Chiu Mu-Lin , Hung Chien-Hui , Liang Wen-Miin , Ho Mao-Wang , Lin Ting-Hsu , Liu Xiang , Tsang Hsinyi , Liao Chiu-Chu , Huang Shao-Mei , Wu Yi-Fang , Wu Yang-Chang , Li Te-Mao , Tsai Fuu-Jen , Lin Ying-Ju
Published: August 2021

Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5′-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5′-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5′-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5′-LTR transcriptional activity. We found that X. strumarium inhibits the 5′-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5′-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5′-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection.
Diabetes and Heart Failure: Multi-Omics Approaches
Authors: Tayanloo-Beik Akram , Roudsari Peyvand Parhizkar , Rezaei-Tavirani Mostafa , Biglar Mahmood , Tabatabaei-Malazy Ozra , Arjmand Babak , Larijani Bagher
Published: August 2021

Diabetes and heart failure, as important global issues, cause substantial expenses to countries and medical systems because of the morbidity and mortality rates. Most people with diabetes suffer from type 2 diabetes, which has an amplifying effect on the prevalence and severity of many health problems such as stroke, neuropathy, retinopathy, kidney injuries, and cardiovascular disease. Type 2 diabetes is one of the cornerstones of heart failure, another health epidemic, with 44% prevalence. Therefore, finding and targeting specific molecular and cellular pathways involved in the pathophysiology of each disease, either in diagnosis or treatment, will be beneficial. For diabetic cardiomyopathy, there are several mechanisms through which clinical heart failure is developed; oxidative stress with mediation of reactive oxygen species (ROS), reduced myocardial perfusion due to endothelial dysfunction, autonomic dysfunction, and metabolic changes, such as impaired glucose levels caused by insulin resistance, are the four main mechanisms. In the field of oxidative stress, advanced glycation end products (AGEs), protein kinase C (PKC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the key mediators that new omics-driven methods can target. Besides, diabetes can affect myocardial function by impairing calcium (Ca) homeostasis, the mechanism in which reduced protein phosphatase 1 (PP1), sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a), and phosphorylated SERCA2a expressions are the main effectors. This article reviewed the recent omics-driven discoveries in the diagnosis and treatment of type 2 diabetes and heart failure with focus on the common molecular mechanisms.
Intestinal Barrier Dysfunction Exacerbates Neuroinflammation via the TLR4 Pathway in Mice With Heart Failure
Authors: Huo Jun-Yu , Jiang Wan-Ying , Yin Ting , Xu Hai , Lyu Yi-Ting , Chen Yuan-Yuan , Chen Meng , Geng Jie , Jiang Zhi-Xin , Shan Qi-Jun
Published: August 2021

Aims

The present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms.

Methods

Male wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF.

Results

Eight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors.

Conclusion

HF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.
Chloroplast Phylogenomic Analyses Resolve Multiple Origins of the Kengyilia Species (Poaceae: Triticeae) via Independent Polyploidization Events
Authors: Chen Shiyong , Yan Hao , Sha Lina , Chen Ning , Zhang Haiqin , Zhou Yonghong , Fan Xing
Published: August 2021

Kengyiliais a group of allohexaploid species that arose from two hybridization events followed by genome doubling of three ancestral diploid species with different genomes St, Y, and P in the Triticeae. Estimating the phylogenetic relationship in resolution of the maternal lineages has been difficult, owing to the extremely low rate of sequence divergence. Here, phylogenetic reconstructions based on the plastome sequences were used to explore the role of maternal progenitors in the establishment ofKengyiliapolyploid species. The plastome sequences of 11Kengyiliaspecies were analyzed together with 12 tetraploid species (PP, StP, and StY) and 33 diploid taxa representing 20 basic genomes in the Triticeae. Phylogenomic analysis and genetic divergence patterns suggested that (1)Kengyiliais closely related toRoegneria,Pseudoroegneria,Agropyron,Lophopyrum,Thinopyrum, andDasypyrum; (2) both the StY genomeRoegneriatetraploids and the PP genomeAgropyrontetraploids served as the maternal donors during the speciation ofKengyiliaspecies; (3) the differentKengyiliaspecies derived their StY genome from differentRoegneriaspecies. Multiple origins of speciesviaindependent polyploidization events have occurred in the genusKengyilia, resulting in a maternal haplotype polymorphism. This helps explain the rich diversity and wide adaptation of polyploid species in the genusKengyilia.
Genome-Wide Identification of TCP Transcription Factors Family in Sweet Potato Reveals Significant Roles of miR319-Targeted TCPs in Leaf Anatomical Morphology
Authors: Ren Lei , Wu Haixia , Zhang Tingting , Ge Xinyu , Wang Tianlong , Zhou Wuyu , Zhang Lei , Ma Daifu , Wang Aimin
Published: August 2021

Plant-specific TCP transcription factors play vital roles in the controlling of growth, development, and the stress response processes. Extensive researches have been carried out in numerous species, however, there hasn’t been any information available about TCP genes in sweet potato (Ipomoea batatas L.). In this study, a genome-wide analysis of TCP genes was carried out to explore the evolution and function in sweet potato. Altogether, 18 IbTCPs were identified and cloned. The expression profiles of the IbTCPs differed dramatically in different organs or different stages of leaf development. Furthermore, four CIN-clade IbTCP genes contained miR319-binding sites. Blocking IbmiR319 significantly increased the expression level of IbTCP11/17 and resulted in a decreased photosynthetic rate due to the change in leaf submicroscopic structure, indicating the significance of IbmiR319-targeted IbTCPs in leaf anatomical morphology. A systematic analyzation on the characterization of the IbTCPs together with the primary functions in leaf anatomical morphology were conducted to afford a basis for further study of the IbmiR319/IbTCP module in association with leaf anatomical morphology in sweet potato.
Reserve Accumulation Is Prioritized Over Growth Following Single or Combined Injuries in Three Common North American Urban Tree Species
Authors: Ramirez Jorge Andres , Vitali Valentina , Martínez-Vilalta Jordi , Handa I. Tanya , Messier Christian
Published: August 2021

Trees that grow in urban areas are confronted with a wide variety of stresses that undermine their long-term survival. These include mechanical damage to the crown, root reduction and stem injury, all of which remove significant parts of plant tissues. The single or combined effects of these stresses generate a complex array of growth and ecophysiological responses that are hard to predict. Here we evaluated the effects of different individual and combined damage on the dynamics of non-structural carbohydrates (NSC, low weight sugars plus starch) concentration and new tissue growth (diameter increment) in young trees. We hypothesized that (i) tissue damage will induce larger reductions in diameter growth than in NSC concentrations and (ii) combinations of stress treatments that minimally alter the “functional equilibrium” (e.g., similar reductions of leaf and root area) would have the least impact on NSC concentrations (although not on growth) helping to maintain tree health and integrity. To test these hypotheses, we set up a manipulative field experiment with 10-year-old trees of common urban species (Celtis occidentalis, Fraxinus pennsylvanica, and Tilia cordata). These trees were treated with a complete array of mechanical damage combinations at different levels of intensity (i.e., three levels of defoliation and root reduction, and two levels of stem damage). We found that tree growth declined in relation to the total amount of stress inflicted on the trees, i.e., when the combined highest level of stress was applied, but NSC concentrations were either not affected or, in some cases, increased with an increasing level of stress. We did not find a consistent response in concentration of reserves in relation to the combined stress treatments. Therefore, trees appear to reach a new “functional equilibrium” that allows them to adjust their levels of carbohydrate reserves, especially in stems and roots, to meet their metabolic demand under stressful situations. Our results provide a unique insight into the carbon economy of trees facing multiple urban stress conditions in order to better predict long-term tree performance and vitality.
Novel Effector RHIFs Identified From Acidovorax avenae Strains N1141 and K1 Play Different Roles in Host and Non-host Plants
Authors: Nakamura Minami , Kondo Machiko , Suzuki Aika , Hirai Hiroyuki , Che Fang-Sik
Published: August 2021

Plant pathogenic bacteria inject effectors into plant cells using type III secretion systems (T3SS) to evade plant immune systems and facilitate infection. In contrast, plants have evolved defense systems called effector-triggered immunity (ETI) that can detect such effectors during co-evolution with pathogens. The rice-avirulent strain N1141 of the bacterial pathogen Acidovorax avenae causes rice ETI, including hypersensitive response (HR) cell death in a T3SS-dependent manner, suggesting that strain N1141 expresses an ETI-inducing effector. By screening 6,200 transposon-tagged N1141 mutants based on their ability to induce HR cell death, we identified 17 mutants lacking this ability. Sequence analysis and T3SS-mediated intracellular transport showed that a protein called rice HR cell death inducing factor (RHIF) is a candidate effector protein that causes HR cell death in rice. RHIF-disrupted N1141 lacks the ability to induce HR cell death, whereas RHIF expression in this mutant complemented this ability. In contrast, RHIF from rice-virulent strain K1 functions as an ETI inducer in the non-host plant finger millet. Furthermore, inoculation of rice and finger millet with either RHIF-deficient N1141 or K1 strains showed that a deficiency of RHIF genes in both strains results in decreased infectivity toward each the host plants. Collectively, novel effector RHIFs identified from A. avenae strains N1141 and K1 function in establishing infection in host plants and in ETI induction in non-host plants.
Financial and Mental Health Concerns of Impoverished Urban-Dwelling Bangladeshi People During COVID-19
Authors: Islam Md. Saiful , Rahman Md. Estiar , Banik Rajon , Emran Md. Galib Ishraq , Saiara Noshin , Hossain Sahadat , Hasan M. Tasdik , Sikder Md. Tajuddin , Smith Lee , Potenza Marc N.
Published: August 2021

Background: The COVID-19 pandemic has impacted the physical, mental and financial health of many individuals. Individuals living in impoverished crowded settings may be particularly vulnerable to COVID-19-related stressors. How substantially marginalized groups like impoverished urban-dwelling individuals have been impacted during this pandemic is poorly understood. The present study aimed to investigate the associated factors of financial concerns and symptoms of depression and posttraumatic stress disorder (PTSD) during the COVID-19 pandemic among impoverished urban-dwelling individuals residing in Dhaka, Bangladesh.

Methods: A cross-sectional survey was conducted between August and September 2020 using face-to-face interviews in six disadvantaged neighborhoods (“slums”) in Dhaka. Individuals were interviewed using a semi-structured questionnaire consisting of questions assessing socio-demographics, lifestyle, financial well-being relating to the COVID-19 pandemic, depression, and PTSD.

Results: Four-hundred-and-thirty-five individuals (male = 54.7%; mean age = 45.0 ± 12.0 years; age range = 18–85 years) participated. Most (96.3%) reported that their household income decreased due to the COVID-19 pandemic. Factors associated with decreased household incomes included female gender, primary education, joblessness, food scarcity and depression. Depression symptoms were linked to female gender, joblessness, divorce, living in a joint family, excessive sleep and smoking. Low incomes, excessive sleep, joblessness and food scarcity were positively associated with PTSD symptoms. In contrast, less sleep appeared protective against PTSD.

Conclusions: Public health initiatives, in particular mental health services that target stress and biocentric approaches that consider how humans interact with multiple facets of nature, should be introduced to mitigate against potential financial and psychological effects of the pandemic on impoverished urban-dwelling individuals in Bangladesh.