bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurodynamic correlates for the cross-frequency coupled transcranial alternating current stimulation during working memory performance
Authors: Kim Seong-Eun , Kim Hyun-Seok , Kwak Youngchul , Ahn Min-Hee , Choi Kyung Mook , Min Byoung-Kyong
Published: October 2022

Transcranial current stimulation is a neuromodulation technique used to modulate brain oscillations and, in turn, to enhance human cognitive function in a non-invasive manner. This study investigated whether cross-frequency coupled transcranial alternating current stimulation (CFC-tACS) improved working memory performance. Participants in both the tACS-treated and sham groups were instructed to perform a modified Sternberg task, where a combination of letters and digits was presented. Theta-phase/high-gamma-amplitude CFC-tACS was administered over electrode F3 and its four surrounding return electrodes (Fp1, Fz, F7, and C3) for 20 min. To identify neurophysiological correlates for the tACS-mediated enhancement of working memory performance, we analyzed EEG alpha and theta power, cross-frequency coupling, functional connectivity, and nodal efficiency during the retention period of the working memory task. We observed significantly reduced reaction times in the tACS-treated group, with suppressed treatment-mediated differences in frontal alpha power and unidirectional Fz-delta-phase to Oz-high-gamma-amplitude modulation during the second half of the retention period when network analyses revealed tACS-mediated fronto-occipital dissociative neurodynamics between alpha suppression and delta/theta enhancement. These findings indicate that tACS modulated top-down control and functional connectivity across the fronto-occipital regions, resulting in improved working memory performance. Our observations are indicative of the feasibility of enhancing cognitive performance by the CFC-formed tACS.
A bioinspired configurable cochlea based on memristors
Authors: Cheng Lingli , Gao Lili , Zhang Xumeng , Wu Zuheng , Zhu Jiaxue , Yu Zhaoan , Yang Yue , Ding Yanting , Li Chao , Zhu Fangduo , Wu Guangjian , Zhou Keji , Wang Ming , Shi Tuo , Liu Qi
Published: October 2022

Cochleas are the basis for biology to process and recognize speech information, emulating which with electronic devices helps us construct high-efficient intelligent voice systems. Memristor provides novel physics for performing neuromorphic engineering beyond complementary metal-oxide-semiconductor technology. This work presents an artificial cochlea based on the shallen-key filter model configured with memristors, in which one filter emulates one channel. We first fabricate a memristor with the TiN/HfOx/TaOx/TiN structure to implement such a cochlea and demonstrate the non-volatile multilevel states through electrical operations. Then, we build the shallen-key filter circuit and experimentally demonstrate the frequency-selection function of cochlea’s five channels, whose central frequency is determined by the memristor’s resistance. To further demonstrate the feasibility of the cochlea for system applications, we use it to extract the speech signal features and then combine it with a convolutional neural network to recognize the Free Spoken Digit Dataset. The recognition accuracy reaches 92% with 64 channels, compatible with the traditional 64 Fourier transform transformation points of mel-frequency cepstral coefficients method with 95% recognition accuracy. This work provides a novel strategy for building cochleas, which has a great potential to conduct configurable, high-parallel, and high-efficient auditory systems for neuromorphic robots.
Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
Authors: Niu Yan , Chang Pan , Liu Tian , Shen Xi , Zhao Hui , Zhang Mingxia , Lei Shengping , Chen Baoying , Yu Jun
Published: October 2022

Obesity induced by a high-fat diet (HFD) is an important cause of impaired memory and cognitive function, but the underlying mechanisms are not clear. In the present study, we analyzed the levels of circRNAs in the hippocampus of C57BL/6J mice and evaluated the memory and cognition ability of C57BL/6J mice with HFD using Morris water maze and Y-maze approaches to explore the potential mechanisms linking circRNAs in obesity-associated cognitive impairment. Learning performance showed that HFD-induced obesity mice have impaired memory and cognition. The Arraystar analysis of the hippocampus displayed that HFD-induced obesity leads to the differential expression of circRNAs (DE-circRNAs) in mice. In total, 46 circular RNAs with elevated expression and 10 with decreased expression were identified. Among them, mmu_circRNA_004797 was identified to be significantly downregulated and the expression of mmu_circRNA_21040 was significantly upregulated in the HFD-fed mice, compared with control mice by PCR test. Bioinformatics analysis also showed that the upregulated circRNAs were related to the neuronal function and behavior, and material transport process, while downregulated circRNAs participated in the process of cell response to external stimuli, such as cellular response to nutrient levels. Furthermore, the KEGG pathway analysis showed that the upregulated circRNAs are mainly involved in Axon guidance, calcium signaling pathway, and ErbB signaling pathway. Only a single significant pathway, that is, “protein processing in endoplasmic reticulum”, was observed in the downregulated circRNAs. Finally, we examined the deficits of hippocampal synaptic plasticity and detected the expression of ER stress-related protein. The results showed that ER stress was activated in the hippocampus, and hippocampal synaptic plasticity deficits were displayed. Our results demonstrated that circRNAs were most likely implicated in the predisposition to obesity-associated cognitive impairment.
Antimicrobial activities and mechanism of sturgeon spermary protein extracts against Escherichia coli
Authors: Chen Ya-Nan , Li Hai-Lan , Huang Jia-Jun , Li Mei-Jin , Liao Tao , Zu Xiao-Yan
Published: October 2022

This study aimed to evaluate the antimicrobial activities and mechanism of sturgeon spermary protein extracts (SSPE) against Escherichia coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. Cell structural change was analyzed using scanning electron microscopy-energy dispersive X-ray spectrometry and transmission electron microscope. Moreover, pH, zeta potential, membrane potential, intracellular ATP concentrations and the interaction of SSPE with genomic DNA were analyzed. Results showed that molecular weight of SSPE is 13.4 kDa, the content of basic amino acids is the highest, in which arginine accounts for 73.2%. The MIC and MBC of SSPE for E. coli were 0.05 and 5 mg/mL, respectively. After SSPE treatment, cell membrane permeability changes, zeta potential decrease and genomic DNA lysis occurred in E. coli, which indicated it exerted bacteriostatic effects either independently or simultaneously by destroying the cell membrane and genomic DNA. These findings indicated that SSPE has potential to be a natural antiseptic.
Characterization of volatile thiols in Chinese liquor (Baijiu) by ultraperformance liquid chromatography–mass spectrometry and ultraperformance liquid chromatography–quadrupole-time-of-flight mass spectrometry
Authors: Yan Yan , Lu Jun , Nie Yao , Li Changwen , Chen Shuang , Xu Yan
Published: October 2022

Volatile thiols give a unique flavor to foods and they have been extensively studied due to their effects on sensory properties. The analytical assay of volatile thiols in food is hindered by the complexity of the matrix, and by both their high reactivity and their typically low concentrations. A new ultraperformance liquid chromatography (UPLC) strategy has been developed for the identification and quantification of volatile thiols in Chinese liquor (Baijiu). 4,4’-Dithiodipyridine reacted rapidly with eight known thiols to form derivatives, which provided a diagnostic fragment ion (m/z 143.5) for tandem mass spectrometry (MS/MS). To screen for new thiols, Baijiu samples were analyzed by means of UPLC–MS/MS screening for compounds exhibiting the diagnostic fragment ion (m/z X→143.5). New peaks with precursor ions of m/z 244, 200 and 214 were detected. Using UPLC with quadrupole-time-of-flight mass spectrometry (UPLC–Q-TOF–MS) and authentic standards, ethyl 2-mercaptoacetate, 1-butanethiol, and 1-pentanethiol were identified in Baijiu for the first time. Commercial Baijiu samples were analyzed with the new method and the distribution of 11 thiols was revealed in different Baijiu aroma-types. The aroma contribution of these thiols was evaluated by their odoractivity values (OAVs), with the result that 7 of 11 volatile thiols had OAVs > 1. In particular, methanethiol, 2-furfurylthiol, and 2-methyl-3-furanthiol had relatively high OAVs, indicating that they contribute significantly to the aroma profile of Baijiu.
Framing the futures of animal-free dairy: Using focus groups to explore early-adopter perceptions of the precision fermentation process
Authors: Broad Garrett M. , Zollman Thomas Oscar , Dillard Courtney , Bowman Daniel , Le Roy Brice
Published: October 2022

This paper reports on the findings from a series of virtual focus groups that explored consumer perceptions of animal-free dairy (AFD), an emerging type of animal product alternative produced using the tools of synthetic biology and precision fermentation. Focus group participants came from an international sample of potential “early adopters.” To stimulate conversation, participants were presented with a series of visual “moodboards” that framed key arguments both in favor of and in opposition to AFD. Three primary thematic clusters emerged from the discussion. The first focused on issues of “process, safety, and regulation,” centered on the general reaction of participants to the concept of AFD, their primary concerns, key questions, and the assurances they would need in order to support its advancement. The second focused on issues of “consumer preferences and priorities,” highlighted by the often complicated, and sometimes outright contradictory, stated consumer interests of the participants. The third focused on issues of “food technology and the future,” wherein participants expressed broader views on the role of food technology in society, generally speaking, and the potential futures of AFD, specifically. The general consensus among participants was a cautious openness to the idea of AFD. Outright opposition to the concept was rare, but so too was unabashed enthusiasm. Instead, respondents had a number of questions about the nature of the technological process, its overall safety and regulatory standards, its potential contributions to individual health and climate change mitigation, as well as its organoleptic qualities and price to consumers. Among the positive frames, claims about animal welfare were deemed the most pertinent and convincing. Among the negative frames, concerns about messing with nature and creating potential health risks to individuals were seen as the strongest arguments against AFD. The findings suggest that the key to AFD's future as a viable market option will depend in large part on the extent to which it can clearly demonstrate that it is preferable to conventional dairy or its plant-based competitors, particularly in the arena of taste, but also across considerations of health and safety, nutrition, environmental effects, and animal well-being.
Survival, response rates, and post-transplant outcomes in patients with Acute Myeloid Leukemia aged 60-75 treated with high intensity chemotherapy vs. lower intensity targeted therapy
Authors: Sahasrabudhe Kieran , Huang Ying , Rebechi Melanie , Elder Patrick , Mims Alice , Wall Sarah
Published: October 2022

The United States Food and Drug Administration has approved several oral, targeted therapies for the treatment of Acute Myeloid Leukemia (AML) in recent years. These agents are approved in patients with relapsed/refractory disease or as frontline therapy in patients who are ineligible for intensive chemotherapy based on age, performance status, or comorbidities. They are also being increasingly utilized frontline in patients of all ages and fitness levels through clinical trials and off label prescribing, but comparative treatment outcomes associated with intensive versus targeted therapy have not been extensively studied. We conducted a single center, retrospective analysis to address the impact of treatment intensity on survival in patients with AML aged 60-75 at diagnosis. This study included 127 patients, 73 of whom received high intensity chemotherapy at any point during treatment (any HiC) and 54 of whom received only low intensity targeted therapy (LITT only). Overall survival (OS) from treatment initiation did not differ significantly between the any HiC and LITT only groups (hazard ratio (HR) for death, 0.67; 95% CI, 0.41 to 1.09; P=0.11). The only three variables that were independently associated with superior OS were lower European Leukemia Net (ELN) risk classification, TP53 unmutated status, and receipt of transplant. Our data suggest that baseline genomic features and receipt of transplant are more important than treatment intensity in predicting survival in this patient population. They also highlight the vital role of transplant in older patients with AML regardless of treatment intensity utilized for remission induction. Larger studies are needed to further address this question, including prospective randomized trials.
Prognostic value of mesorectal package area in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy: A retrospective cohort study
Authors: Guan Bingjie , Huang Xinmin , Xia Huang , Guan Guoxian , Xu Benhua
Published: October 2022

Background

The aim of this study is to explore the most effective inflammation, magnetic resonance imaging (MRI), and nutrition markers for survival and pathology complete response (pCR) in patients with locally advanced rectal cancer (LARC).

Methods

A total of 278 patients with LARC undergoing neoadjuvant chemoradiotherapy (NCRT) and radical surgery from 2016 to 2019 were included. The X-tile method was used to select the optimal cutoff points for the mesorectal package area (MPA), advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) scores. Cox regression analysis was used to identify risk factors of disease-free survival (DFS). To discover pCR risk factors, logistic regression analysis was employed. A predictive nomogram for DFS was constructed.

Results

According to the least absolute shrinkage and selection operator analysis, the MPA was the only significant predictor for the DFS in patients with LARC. Kaplan-Meier (K-M) analysis demonstrated that groups with higher MPA, PNI, SII, NLR, MLR, and ALI score had improved DFS (all P < 0.05). Receiver operating characteristic (ROC) analysis revealed that the MPA and PNI could accurately predict the pCR in patients with LARC after NCRT. The MPA score and NLR score were found to be independent predictors of DFS after NCRT using Cox regression analysis. Logistical regression analysis demonstrated that the MPA score, PNI score, and pre-NCRT cN stage were all independent predictors of pCR in patients with LARC after NCRT. Recursive partitioning analysis and time-independent ROC curve analysis demonstrated that MPA score was the most important predictor of pCR and prognosis in patients with LARC after NCRT.

Conclusions

MPA was identified as the most effective marker for MRI, and the prognostic value was further confirmed by time–ROC analysis. More intense adjuvant treatment could be considered for lower–MPA score patients with LARC after NCRT. Obesity in the pelvis encourages the understanding of the prognosis prediction of patients with LARC after NCRT.
Comparative analysis of extracellular vesicle isolation methods from human AML bone marrow cells and AML cell lines
Authors: Lang Jonas B. , Buck Michèle C. , Rivière Jennifer , Stambouli Oumaima , Sachenbacher Ken , Choudhary Purva , Dietz Hendrik , Giebel Bernd , Bassermann Florian , Oostendorp Robert A. J. , Götze Katharina S. , Hecker Judith S.
Published: October 2022

Cellular crosstalk between hematopoietic stem/progenitor cells and the bone marrow (BM) niche is vital for the development and maintenance of myeloid malignancies. These compartments can communicate via bidirectional transfer of extracellular vesicles (EVs). EV trafficking in acute myeloid leukemia (AML) plays a crucial role in shaping the BM microenvironment into a leukemia-permissive niche. Although several EV isolation methods have been developed, it remains a major challenge to define the most accurate and reliable procedure. Here, we tested the efficacy and functional assay compatibility of four different EV isolation methods in leukemia-derived EVs: (1) membrane affinity-based: exoEasy Kit alone and (2) in combination with Amicon filtration; (3) precipitation: ExoQuick-TC; and (4) ultracentrifugation (UC). Western blot analysis of EV fractions showed the highest enrichment of EV marker expression (e.g., CD63, HSP70, and TSG101) by precipitation with removal of overabundant soluble proteins [e.g., bovine serum albumin (BSA)], which were not discarded using UC. Besides the presence of damaged EVs after UC, intact EVs were successfully isolated with all methods as evidenced by highly maintained spherical- and cup-shaped vesicles in transmission electron microscopy. Nanoparticle tracking analysis of EV particle size and concentration revealed significant differences in EV isolation efficacy, with exoEasy Kit providing the highest EV yield recovery. Of note, functional assays with exoEasy Kit-isolated EVs showed significant toxicity towards treated target cells [e.g., mesenchymal stromal cells (MSCs)], which was abrogated when combining exoEasy Kit with Amicon filtration. Additionally, MSC treated with green fluorescent protein (GFP)-tagged exoEasy Kit-isolated EVs did not show any EV uptake, while EV isolation by precipitation demonstrated efficient EV internalization. Taken together, the choice of EV isolation procedure significantly impacts the yield and potential functionality of leukemia-derived EVs. The cheapest method (UC) resulted in contaminated and destructed EV fractions, while the isolation method with the highest EV yield (exoEasy Kit) appeared to be incompatible with functional assays. We identified two methods (precipitation-based ExoQuick-TC and membrane affinity-based exoEasy Kit combined with Amicon filtration) yielding pure and intact EVs, also suitable for application in functional assays. This study highlights the importance of selecting the right EV isolation method depending on the desired experimental design.
Sequential pulmonary resections by uniportal video-assisted thoracic surgery for bilateral multiple pulmonary nodules
Authors: Xu Guangwen , Wang Gaoxiang , Mei Xinyu , Wu Mingsheng , Li Tian , Xie Mingran
Published: October 2022

Objective

The aim of this study was to evaluate the effect of sequential pulmonary resections by uniportal video-assisted thoracoscopic surgery (VATS) for bilateral multiple pulmonary nodules (BMPNs).

Methods

A single-center, prospective, nonrandomized study was performed on patients who underwent one-stage or two-stage operations by uniportal VATS. The clinical, pathological and perioperative data were summarized and analyzed from January 2021 to December 2021.

Results

A total of 80 patients were included during the study period. Sequential pulmonary resection by uniportal VATS was underwent in 40 patients. There were no perioperative deaths and serious complications, 2 patients had postoperative pneumonia, 3 patients had transient atrial fibrillation, 1 patient had persistent severe air leakage, 1 patient occurred hemoptysis. The one-stage group had less operative time, surgical blood loss, pleural drainage, chest tube duration and postoperative admission duration(P<0.05). The results of pathological examination of pulmonary nodules revealed adenocarcinoma in situ (n=12), minimally invasive adenocarcinoma (n=24), invasive adenocarcinoma (n=42), squamous carcinoma (n=1),and benign nodules (n=10). The pathological diagnosis included multiple primary lung cancers (30/40, 75%), single primary lung cancer (6/40, 15%). The most advanced pathologic stage of the primary lung cancer was classified as IA (n=19), IB (n=5), II (n=3), and IIIA (n=2).

Conclusion

For patients with excellent pulmonary function, sequential pulmonary resection by uniportal VATS is a safe and feasible for BMPNs. Strict control of surgical indications, reasonable preoperative planning, accurate intraoperative operation, and standardized perioperative management can effectively reduce complications and maximize benefits for suitable patients.
Association of metabolic syndrome and the risk of bladder cancer: A prospective cohort study
Authors: Fang Shuo , Liu Yuchen , Dai Huiru , Gao Tianshun , Zeng Leli , Sun Rui , Zheng Zilong , Yuan Jinqiu , Xia Bin , Pan Yihang
Published: October 2022

Background

Metabolic syndrome (MetS) and its components have been shown as risk factors for several solid cancers. However, current epidemiological evidence about the relevance of MetS and bladder cancer risk was limited.

Methods

We conducted a prospective cohort study of 476,986 participants with undiagnosed bladder cancer based on the UK Biobank. MetS was defined as the presence of at least three of the five selected indicators: hypertension, central obesity, raised triglyceride, reduced HDL-cholesterol, and raised fasting plasma glucose. Bladder cancer has been identified through contact with the British Cancer Registry (median follow-up time: 6.6 years). We assessed hazard ratio (HR) and 95% confidence interval (CI) through Cox proportional hazard regression after adjusting for demographic and lifestyle factors. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method.

Results

During a follow-up of 3,112,566 person-years, 487 cases of bladder cancer were ascertained. MetS (HR = 1.32, 95% CI = 1.08–1.61), central obesity (HR = 1.39, 95% CI = 1.15–1.68), dyslipidemia for HDL cholesterol (HR = 1.31, 95% CI = 1.04–1.66), and hyperglycemia (HR = 1.44, 95% CI = 1.16–1.79) were associated with elevated risk of bladder cancer. Bladder cancer risk increased with the number of MetS components. In stratified analyses, MetS showed similar effects in bladder cancer independently with sex, age, cigarette and alcohol use, physical activity, and dietary factors. Higher waist circumference, BMI, fasting blood glucose, and glycosylated hemoglobin were independently associated with increased risk of bladder cancer, with no evidence against non-linearity.

Conclusion

MetS might be an independent risk factor for bladder cancer. Our findings highlighted the importance of individualized management of MetS components for preventing bladder cancer.
Parents' intention for their children to receive COVID-19 vaccine: Implications for vaccination program in Macao
Authors: Choi Un I , Pang Yimin , Zheng Yu , Tang Pou Kuan , Hu Hao , Ung Carolina Oi Lam
Published: October 2022

Introduction

The decision about vaccinating children is subject to their parents' decision. To inform strategies that support full vaccination coverage, it is important to understand the parents' vaccination attitude and tendency to act. This study aims to investigate the intention and the factors affecting parents' decision-making about vaccinating their children.

Methods

A cross-sectional, self-administered online questionnaire was completed by parents of children aged 3–12 yeas in Macao between 7 March and 17 April 2022. The survey tool was informed by the Theory of Planned Behavior (TPB) which composes of the variable “intention” and three TPB constructs (Attitude, Subjective Norm, andPerceived Behavioral Control). Respondents rated their level of agreement on the construct statements using a 5-point Likert scale. Multiple linear regression analysis was used to determine if the TPB constructs were predictors of parents' intention.

Results

A total of 1,217 parents completed the questionnaire. The majority of participants were mothers (83.2%), aged 31–40 years (62.7%), having two or more children (74.1%), had at least one dose of COVID-19 vaccine (84.4%) and considered themselves knowledgeable about the vaccine (62.1%), all of which were significantly associated with the intention to vaccinate their children (allp< 0.05). Their intention varied from negative (19.1%), neutral (38.4%) to positive (42.5%). Respondents were mostly concerned about the serious side effects that the COVID-19 vaccine (mean = 3.96 ± 1.23), highly acknowledged the expectation by the school (mean = 3.94 ± 1.15) and the community (mean = 3.90 ± 1.19) of children vaccination, and rated highly the ease of making necessary arrangement (mean = 3.93 ± 1.25). In the multiple linear regression model which explained 63.5% of the variance in the intention-to-vaccinate their children, onlyAttitude(B = 0.52,p< 0.001) andSubjective Norm(B = 0.39,p< 0.001) were identified as strong predictors. The major reasons for not having intention were safety concerns (n= 646/699, 92.4%). Participants' most trusted local information sources were doctors (n= 682), government (n= 426) and healthcare professional organizations (n= 416).

Conclusions

Vaccinating children with COVID-19 vaccine is a complex decision-making for parents. A key to a successful COVID-19 vaccination program is effective communication about the safety profile and the usage experiences warranting the integration of reliable information sources across different healthcare sectors.
Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review
Authors: Fischler Pascal Valentin , Soyka Michael , Seifritz Erich , Mutschler Jochen
Published: October 2022

Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene. Although all four are effective in maintaining abstinence or reduction of alcohol consumption, only a small percentage of patients receive pharmacological treatment. In addition, many other medications have been investigated for their therapeutic potential in the treatment of alcohol use disorder. In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropin-releasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will require greater understanding provided by many more preclinical and clinical studies.
The proteolysis targeting chimera GMB-475 combined with dasatinib for the treatment of chronic myeloid leukemia with BCR::ABL1 mutants
Authors: Ye Wu , Wu Xia , Wang Xiaojia , Wei Xiaoyu , Tang Yuqian , Ouyang Xianfeng , Gong Yuping
Published: October 2022

Patients with chronic myeloid leukemia (CML) show resistance to tyrosine kinase inhibitors (TKIs) targeting ABL1 due to the emergence of BCR::ABL1 mutants, especially compound mutants during the treatment, which brings great challenges to clinical practice. Combination therapy is an effective strategy for drug resistance. GMB-475, a proteolysis targeting chimera (PROTAC) targeting the myristoyl pocket of ABL1 in an allosteric manner, degrades the BCR::ABL1 through the ubiquitin–proteasome pathway. In this study, we combined GMB-475 with orthosteric TKIs targeting ABL1 to overcome resistance. We constructed Ba/F3 cells carrying BCR::ABL1 mutants by gene cloning technology and compared the effects of combination therapy with those of monotherapy on the biological characteristics and signaling pathways in CML cells. We found that the effects of ABL1 inhibitors, including imatinib, dasatinib, ponatinib, and ABL001, on growth inhibition and promoting apoptosis of Ba/F3 cells with BCR::ABL1 mutants, especially compound mutants, were weakened. GMB-475 combined with TKIs, especially dasatinib, synergistically inhibited growth, promoted apoptosis, and blocked the cell cycle of Ba/F3 cells carrying BCR::ABL1 mutants and synergistically blocked multiple molecules in the JAK-STAT pathway. In conclusion, dasatinib enhanced the antitumor effect of GMB-475; that is, the combination of PROTAC targeting ABL1 in an allosteric manner and orthosteric TKIs, especially dasatinib, provides a novel idea for the treatment of CML patients with BCR::ABL1 mutants in clinical practice.
Roles and mechanisms of garlic and its extracts on atherosclerosis: A review
Authors: Li Min , Yun Wingyan , Wang Guibin , Li Anqi , Gao Jing , He Qingyong
Published: October 2022

The prevention and treatment of cardiovascular diseases (CVDs) have achieved initial results, but the number of CVDs patients will increase rapidly in the next 10 years. Atherosclerosis (AS) is a significant risk factor for CVDs. The impact of lifestyle and daily diet varies considerably between different countries and continents and has been shown to affect the development of various diseases such as diabetes and CVDs. Primary and secondary prevention using alternative supplements and methods to avoid or reduce the use of traditional pharmacological drugs have also become popular. One of the reasons for this is that pharmacological drugs with lipid-lowering, and blood pressure-lowering effects cause many side effects that may negatively impact the quality of life. Patients are now emphasizing reliance on lifestyle changes to reduce cardiovascular risks. Garlic is a medicinal and edible plant that has been used for a long time. In order to reveal garlic application in the prevention and treatment of AS, reviewing the latest domestic and international studies through searching databases. The result shows that the antiatherogenic role of garlic is eximious. And the mechanisms are mainly related to hypolipidemic, antioxidant, antithrombotic, inhibiting angiogenesis, protecting endothelial cells, anti-inflammatory, anti-apoptotic, inhibiting vascular smooth muscle proliferation, and regulating gut microbiota. The main signaling pathways involve AMPK/TLRs, Keap1/Nrf2, PI3K/AKT, PPARγ/LXRα, GEF-H1/RhoA/Rac, etc. The antiatherogenic actions and molecular mechanism of garlic were reviewed in this study to obtain a robust evidence basis for the clinical application and mechanistic study and provide a theoretical basis for further utilization of garlic.
A-Kinase Anchor Protein 1 deficiency causes mitochondrial dysfunction in mouse model of hyperoxia induced acute lung injury
Authors: Soundararajan Ramani , Hernández-Cuervo Helena , Stearns Timothy M , Griswold Anthony J , Patil Sahebgowda Sidramagowda , Fukumoto Jutaro , Narala Venkata Ramireddy , Galam Lakshmi , Lockey Richard , Kolliputi Narasaiah
Published: October 2022

Background: Critically ill patients on supplemental oxygen therapy eventually develop acute lung injury (ALI). Reactive oxygen species (ROS) produced during ALI perturbs the mitochondrial dynamics resulting in cellular damage. Genetic deletion of the mitochondrial A-kinase anchoring protein 1 (Akap1) in mice resulted in mitochondrial damage, Endoplasmic reticulum (ER) stress, increased expression of mitophagy proteins and pro-inflammatory cytokines, exacerbating hyperoxia-induced Acute Lung Injury (HALI).

Objective: Despite a strong causal link between mitochondrial dysfunction and HALI, the mechanisms governing the disease progression at the transcriptome level is unknown.

Methods: In this study, RNA sequencing (RNA-seq) analysis was carried out using the lungs of Akap1 knockout (Akap1−/−) mice exposed to normoxia or 48 h of hyperoxia followed by quantitative real time PCR and Ingenuity pathway analysis (IPA). Western blot analysis assessed mitochondrial dysfunction, OXPHOS complex (I-V), apoptosis and antioxidant proteins. Mitochondrial enzymatic assays was used to measure the aconitase, fumarase, citrate synthase activities in isolated mitochondria from Akap1−/− vs. Wt mice exposed to hyperoxia.

Results: Transcriptome analysis of Akap1−/− exposed to hyperoxia reveals increases in transcripts encoding electron transport chain (ETC) and tricarboxylic acid cycle (TCA) proteins. Ingenuity pathway analysis (IPA) shows enrichment of mitochondrial dysfunction and oxidative phosphorylation in Akap1−/− mice. Loss of AKAP1, coupled with oxidant injury, significantly decreases the activities of TCA enzymes. Mechanistically, a significant loss of dynamin-related protein 1 (Drp1) phosphorylation at the protein kinase A (PKA) site Serine 637 (Ser637), decreases in Akt phosphorylation at Serine 437 (Ser47) and increase in the expression of pro-apoptotic protein Bax indicate mitochondrial dysfunction. Heme oxygenase-1 (HO-1) levels significantly increased in CD68 positive alveolar macrophages in Akap1−/− lungs, suggesting a strong antioxidant response to hyperoxia.

Conclusion: Overall these results suggest that AKAP1 overexpression and modulation of Drp1 phosphorylation at Ser637 is an important therapeutic strategy for acute lung injury.
Correcting the light extinction effect of fly ash particles on the measurement of NO by TDLAS
Authors: Guo Songjie , Yang Yan , Shao Guodong , Li Zhenghui , Ren Wei , Mo Juehui , Lu Zhimin , Yao Shunchun
Published: October 2022

The measurement of nitric oxide (NO) concentration in power plant flue gas by tunable diode laser absorption spectroscopy (TDLAS) is susceptible to fly ash particles. The presence of fly ash particles causes laser intensity fluctuations and leads to the second harmonic (2f) signal amplitude changes. In this manuscript, we analyzed the influence of particles on the 2f signal and corrected the measurement error of NO concentration by the wavelength modulation-second harmonic (WMS-2f) technique. Specifically, the 2f signal error caused by quartz sand and fly ash particles were measured, and the exponential function representing the peak-to-peak error of the 2f signal was obtained by fitting. Finally, the peak-to-peak value of the 2f signal and the NO concentration were corrected according to the exponential function. After correction, the NO concentration error under the fly ash influence (the particle size in the range of 10–200 μm and the mass concentration is less than 18.26 g/m3) was no more than 2%. This correction method effectively improves the measurement accuracy of NO concentration by the WMS-2f technique in the fly ash environment.
Electromagnetic field computation of multilayer vacuum chambers with physics-informed neural networks
Authors: Fujita Kazuhiro
Published: October 2022

The electromagnetic interaction of a charged particle beam with multilayer vacuum chambers is of particular interest in accelerator physics. This paper presents a deep learning-based approach for calculating electromagnetic fields generated by the beam in infinitely long multilayer vacuum chambers with arbitrary cross section. The presented approach is based on physics-informed neural networks and the surface impedance boundary condition of a multilayer structure derived from the transmission line theory. Deep neural networks (DNNs) are utilized to approximate the solution of partial differential equations (PDEs) describing the physics of electromagnetic fields self-generated by a charged particle beam traveling in a particle accelerator. A residual network is constructed from the output of DNNs, the PDEs and boundary conditions are embedded into the loss function and differential operators are calculated using the automatic differentiation. As a result, the presented approach is regarded to be mesh-free. The approach is applied to circular and elliptical vacuum chambers with a three-layer structure. It is verified in comparison with the recently proposed boundary element method. The effects of chamber geometries and multilayer structure on the beam coupling impedance are demonstrated.
Characterization of amorphous carbon films from 5 nm to 200 nm on single-side polished a-plane sapphire substrates by spectroscopic ellipsometry
Authors: Li Ziqing , Cui Changcai , Zhou Xiaolong , Bian Subiao , Arteaga Oriol , Xu Xipeng
Published: October 2022

In this work, a series of amorphous carbon films were deposited on a-plane sapphire substrates by magnetron sputtering with deposition time from 15 min to 8 h, in order to investigate the thickness and optical properties in the process of growth in a non-destructive way. They were characterized by using Mueller matrix spectroscopic ellipsometry together with topography profilometry and Raman spectroscopy. Two models of a Bruggeman effective medium approximation model and a single Cody-Lorentz oscillator model have been proposed to fit films thickness and optical constants from Ultraviolet (UV) to visible (210 nm–800 nm), and Transmission Electron Microscope (TEM) has been used to verify the proposed model for thickness fitting results. The optical constants of the amorphous carbon film have been determined by fitting together all measurements in samples deposited for 2 h or more, with the film thickness being the only sample-independent parameter. The results show that the thickness from 5 nm to 200 nm can be characterized in a nondestructive way although there is a relatively large thickness error compared with the Transmission Electron Microscope results for thin films (d < 20 nm) when the deposition time is less than 2 h because of the nonuniform deposition in the beginning. The relative error between the TEM and Spectroscopic Ellipsometry results can be reduced to 1% after 4 h sample. That means spectroscopic ellipsometry can still provide an indicator for the trend of thickness growth.
Grazing rest during spring regreening period promotes the ecological restoration of degraded alpine meadow vegetation through enhanced plant photosynthesis and respiration
Authors: Liu Ying
Published: October 2022

Grazing rest during the spring regreening period is the most economical and feasible measure for the ecological restoration of degraded alpine meadows and has been widely popularized and applied in China. The aim of the present study was to undertake a comparative analysis of the effects of grazing rest on the ecological restoration of degraded alpine meadows by plant photosynthesis and respiration. Coverage, height, ground biomass, belowground biomass of degraded alpine meadow vegetation, net photosynthetic rate, stomatal conductance, transpiration rate, intercellular CO2 concentration, chlorophyll fluorescence parameters, relative chlorophyll content, respiration rate, metabolite content, leaf relative water content, and related mineral element content of the dominant grass Elymus nutans Griseb. were measured in degraded alpine grassland with different grazing rest years. The results show that grazing rest during the spring regreening period promoted the ecological restoration of degraded alpine meadows by enhancing the photosynthesis and respiration of the dominant grass E. nutans Griseb. Grazing rest enhanced photosynthesis in dominant grass by increasing metabolites related to the Calvin cycle, chlorophyll content, leaf relative water content, and related mineral element content. Grazing at rest enhanced the respiration of dominant grass by increasing metabolites related to the TCA cycle, leaf relative water content, and related mineral element content. This positive effect gradually became stable with increasing years of grazing rest. Our results provide a fundamental basis for the popularization and application of grazing rest during the spring regreening period on degraded Tibetan Plateau grasslands.
Functional characterization of a cell wall invertase inhibitor StInvInh1 revealed its involvement in potato microtuber size in vitro
Authors: Liu Cheng , Hu Shuting , Liu Shuyi , Shi Weiling , Xie Debin , Chen Qi , Sun Hui , Song Linjing , Li Ziyu , Jiang Rui , Lv Dianqiu , Wang Jichun , Liu Xun
Published: October 2022

Cell wall invertase (CWI) is as an essential coordinator in carbohydrate partitioning and sink strength determination, thereby playing key roles in plant development. Emerging evidence revealed that the subtle regulation of CWI activity considerably depends on the post-translational mechanism by their inhibitors (INHs). In our previous research, two putative INHs (StInvInh1 and StInvInh3) were expected as targets of CWI in potato (Solanum tubersum), a model species of tuberous plants. Here, transcript analysis revealed that StInvInh1 showed an overall higher expression than StInhInh3 in all tested organs. Then, StInvInh1 was further selected to study. In accordance with this, the activity of StInvInh1 promoter increased with the development of leaves in plantlets but decreased with the development of microtubers in vitro and mainly appeared in vascular bundle. The recombinant protein StInvInh1 displayed inhibitory activities on the extracted CWI in vitro and StInvInh1 interacted with a CWI StcwINV2 in vivo by bimolecular fluorescence complementation. Furthermore, silencing StInvInh1 in potato dramatically increased the CWI activity without changing activities of vacuolar and cytoplasmic invertase, indicating that StInvInh1 functions as a typical INH of CWI. Releasing CWI activity in StInvInh1 RNA interference transgenic potato led to improvements in potato microtuber size in coordination with higher accumulations of dry matter in vitro. Taken together, these findings demonstrate that StInvInh1 encodes an INH of CWI and regulates the microtuber development process through fine-tuning apoplastic sucrose metabolism, which may provide new insights into tuber development.
The effects of social capital on entrepreneurial resilience of SME from China: A moderated mediation model of entrepreneurial passion and Confucian traditional golden-mean thinking
Authors: Shan Tingting , Tian Xiaoya
Published: October 2022

Small and medium-sized startups play a crucial role in a country's sustainable development. SMEs are at an early development stage, which means weaker institutional norms and successful paradigms, tending to suffer from exceptionally high failure rates because of many constraints, including a lack of resources and credit to access the core information. The higher the environmental uncertainty, the more likely that new start-ups rely on all kinds of social links for acquiring resources. As a critical ability to withstand and overcome obstacles, entrepreneurial resilience is an essential personal characteristic to ensure the sustainability of new ventures. The purpose of this study is to investigate the internal mechanism through which SME entrepreneurs' social capital affects entrepreneurial resilience. To reveal the internal mechanism, we propose a moderated and mediation model. Using survey data from SEM entrepreneurs in China, hierarchical regression analysis and bootstrapping model are adapted to test and verify mediation and moderation effects. The results show that social capital indeed positively influences entrepreneurial resilience directly and partly through the mediating effect of harmonious entrepreneurial passion and obsessive entrepreneurial passion. Moreover, findings suggest golden-mean thinking negatively moderates the relationship between obsessive entrepreneurial passion and entrepreneurial resilience yet positively moderates the relationship between social capital and entrepreneurial resilience. Based on these findings, we conclude that entrepreneurial resilience may be achieved more effectively through the complex internal process of social capital, entrepreneurial passion, and golden-mean thinking. Finally, the study proposes the theoretical and practical implications and suggestions for follow-up research.
Social isolation in adults with cancer: An evolutionary concept analysis
Authors: Liang Yanjing , Hao Guihua , Wu Mei , Hou Lili
Published: October 2022

Background

In extant literature, the concept of social isolation has been explored primarily in the context of older adults. However, people with cancer may also experience social isolation, and there is a need for increased clarity regarding this phenomenon in this population.

Objective

To conceptualize social isolation in adult cancer care.

Methods

PubMed, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure, Wanfang Data, and the Chinese Biomedical Literature Database were systematically searched using the key terms “cancer,” “social isolation,” “social alienation,” and “social exclusion” for studies (from the earliest date available to June 2022). The main disciplines involved were psychology, nursing, medicine, and public health. Rodgers’ evolutionary concept analysis was employed to clarify the antecedents, attributes, and consequences of social isolation in adults with cancer.

Results

A total of 60 eligible articles were reviewed entirely and the main findings were categorized into antecedents, attributes, and consequences. The antecedents of social isolation were classified into six categories: cancer-related physiological changes, cognitive beliefs, psychological wellbeing, unsatisfactory social supports or relationships, restrictions associated with receiving treatments, and social-level barriers. Attributes were characterized according to behavior or social avoidance and negative affective experiences, while consequences were attributed to low therapeutic compliance, poor health conditions and mental health problems, and low quality of life. White’s heuristic model is a potential theoretical context applicable to social isolation in adults with cancer.

Conclusion

This concept analysis provides a basis for developing multidimensional assessment tools and measures to alleviate social isolation in adults with cancer, a complex and varied phenomenon. However, while this review contributes to the current knowledge on social isolation in people with cancer, studies should further investigate the relationships among attributes associated with social isolation.