bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study on Mechanical Properties and Cracking Behaviors of T-Shaped Flaw-Contained Rock-like Materials Under Cyclic Loading
Authors: Cui Lan , Liu Yi , Sheng Qian , Xiao Ping
Published: October 2021

Geotechnical hazards such as debris flows, rock falls in slopes, rock collapse, and rockburst in underground mining or caverns are tightly correlated to the mechanical behavior of natural rock mass stability. Strength and failure mode of the natural rock mass are governed by the presented fissures. In this paper, samples containing T-shaped fissures with different geometry were prepared by rock-like materials and tested under varying uniaxial cyclic loading compression. The effect of T-shaped fissures with different geometry and the strain rate and loading frequency on the strength of tested samples were studied, and the failure mode of the samples containing T-shaped cross fissures under different working conditions was observed. The results show that the function of the minor fissures was not completely negative, and the strength of T-shaped fissure samples containing a major fissure with different inclination angles presented a varying trend with the increasing included angle between the major and minor fissures. Moreover, the strength of the cracked samples increased with the increase of the strain rate and loading frequency, and the larger the included angles between the major and minor fissures, the more sensitive the T-shaped fissure sample was to the change of frequency, but without a noticeable linear correlation relationship between the strength of the sample and the included angles between the major and minor fissures. In addition, the existence of the minor fissures had a significant impact on the failure mode of the sample, and the failure mode of the samples containing T-shaped cross fissures of the same geometry under the uniaxial compression and the uniaxial cyclic load was equivalent.
Carbon Emissions Peak in the Road and Marine Transportation Sectors in View of Cost-Benefit Analysis: A Case of Guangdong Province in China
Authors: Zhao Yongming , Ding Hui , Lin Xiaofang , Li Li , Liao Wenyuan , Liu Yonghong
Published: October 2021

The road and marine transportation sectors have attracted a great deal of attention as one of the main sources of carbon emissions. In this study, a LEAP (long-range energy alternatives planning system) model is used to predict the energy demand and carbon emissions of the road and marine transportation sectors in Guangdong Province from 2016 to 2030. Based on the model results, if Guangdong Province does not adopt new control measures, in 2030, the energy demand and CO2 (carbon dioxide) emissions from the road and marine transportation sectors will have increased by 117 and 116%, respectively, compared to the levels in 2015. Conversely, under a low-carbon scenario, carbon emissions will peak by 2027 in Guangdong Province. Motor vehicle control measures generate the strongest reduction in energy consumption and CO2 emissions for the road and marine transportation sectors in Guangdong Province. Furthermore, the reduction of emissions resulting from these measures would increase over time. Public transportation development and the promotion of clean energy measures also play significant roles in reducing carbon emissions long-term. The contribution of road passenger transport to emission reduction is the largest, followed by marine freight transport and road freight transport. While the energy demand and carbon emissions peak at a similar time in the model, the peak time for CO2 occurs slightly earlier.
Indirect Effects of the Herbicide Glyphosate on Plant, Animal and Human Health Through its Effects on Microbial Communities
Authors: van Bruggen A. H. C. , Finckh M. R. , He M. , Ritsema C. J. , Harkes P. , Knuth D. , Geissen V.
Published: October 2021

The herbicide glyphosate interferes with the shikimate pathway in plants and in major groups of microorganisms impeding the production of aromatic amino acids. Glyphosate application on plants results in a slow death, accelerated by reduced resistance to root pathogens. Extensive glyphosate use has resulted in increasing residues in soil and waterways. Although direct glyphosate effects on animals are limited, major concerns have arisen about indirect harmful side effects. In this paper, we focus on indirect effects of sublethal concentrations of glyphosate on plant, animal and human health due to shifts in microbial community compositions in successive habitats. Research results of glyphosate effects on microbial communities in soil, rhizosphere and animal guts have been contradictory due to the different integration levels studied. Most glyphosate studies have tested short-term treatment effects on microbial biomass or general community composition at higher taxonomic levels in soil, rhizosphere or animal intestinal tracts, and found little effect. More detailed studies showed reductions in specific genera or species as well as biological processes after glyphosate application. Plant growth promoting rhizobacteria and beneficial intestinal bacteria often are negatively affected, while pathogenic bacteria and fungi are enhanced. Such shifts in microbial community composition have been implicated in enhanced susceptibility of plants to Fusarium and Rhizoctonia, of birds and mammals to toxic Clostridium and Salmonella species, and of bees to Serratia and Deformed Wing Virus. In animals and humans, glyphosate exposure and concentrations in urine have been associated with intestinal diseases and neurological as well as endocrine problems, but cause-effect relationships need to be determined in more detail. Nevertheless, outbreaks of several animal and plant diseases have been related to glyphosate accumulation in the environment. Long-term glyphosate effects have been underreported, and new standards will be needed for residues in plant and animal products and the environment.
MiR-320d Inhibits Progression of EGFR-Positive Colorectal Cancer by Targeting TUSC3
Authors: Yufeng Zhu , Ming Qi , Dandan Wu
Published: October 2021

Background: The mechanism of miR-320d in EGFR-positive colorectal cancer (CRC) has not been fully elucidated. The aim of the present study was to explore the molecular mechanism of miR-320d in CRC.

Methods: The miRNA microarray analysis was conducted to identify differential expressed miRNAs. The expression of miR-320d was validated using quantitative real-time PCR. EGFR-positive CRC cells were transfected with miR-320d mimic and inhibitor, after which cell proliferation, migration, and invasion were assayed. The relationship between miR-320d and TUSC3 was confirmed using bioinformatics and dual-luciferase reporter gene assays. Proteins involved in signaling pathways and the epithelial–mesenchymal transition were detected with Western blot.

Results: We found that the miR-320d expression is associated with tumor size and distant metastasis in colorectal cancer. Overexpression of miR-320d in EGFR-positive HCT-116 and SW480 cells decreased not only the proliferation ability but also the invasion and migration ability. In addition, miR-320d had the ability to inhibit epithelial-to-mesenchymal transition. Luciferase assays revealed that miR-320d directly targets the 3′-UTR of TUSC3. TUSC3 was downregulated by miR-320d at both the protein and mRNA levels in EGFR-positive CRC cell lines.

Conclusion: Generally, our results demonstrated that miR-320d could inhibit the malignant phenotype of EGFR-positive CRC through targeting TUSC3. The miR-320d might be a potential therapeutic target for EGFR-positive CRC.
β2-Adrenergic Receptor Enhances the Alternatively Activated Macrophages and Promotes Biliary Injuries Caused by Helminth Infection
Authors: Koda Stephane , Zhang Beibei , Zhou Qian-Yang , Xu Na , Li Jing , Liu Ji-Xin , Liu Man , Lv Zi-Yan , Wang Jian-Ling , Shi Yanbiao , Gao Sijia , Yu Qian , Li Xiang-Yang , Xu Yin-Hai , Chen Jia-Xu , Tekengne B. Oneill Telakeng , Adzika Gabriel K. , Tang Ren-Xian , Sun Hong , Zheng Kui-Yang , Yan Chao
Published: October 2021

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that β2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, β2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow–derived macrophages revealed that macrophages from Adrb2−/− mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+. This study provides a better understanding of the mechanisms by which the β2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.
Exchange Protein Directly Activated by cAMP 2 Enhances Respiratory Syncytial Virus-Induced Pulmonary Disease in Mice
Authors: Ren Junping , Wu Wenzhe , Zhang Ke , Choi Eun-Jin , Wang Pingyuan , Ivanciuc Teodora , Peniche Alex , Qian Youwen , Garofalo Roberto P. , Zhou Jia , Bao Xiaoyong
Published: October 2021

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children. It is also a significant contributor to upper respiratory tract infections, therefore, a major cause for visits to the pediatrician. High morbidity and mortality are associated with high-risk populations including premature infants, the elderly, and the immunocompromised. However, no effective and specific treatment is available. Recently, we discovered that an exchange protein directly activated by cyclic AMP 2 (EPAC2) can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, EPAC2 promotes RSV replication and pro-inflammatory cytokine/chemokine induction. However, the overall role of EPAC2 in the pulmonary responses to RSV has not been investigated. Herein, we found that EPAC2-deficient mice (KO) or mice treated with an EPAC2-specific inhibitor showed a significant decrease in body weight loss, airway hyperresponsiveness, and pulmonary inflammation, compared with wild-type (WT) or vehicle-treated mice. Overall, this study demonstrates the critical contribution of the EPAC2-mediated pathway to airway diseases in experimental RSV infection, suggesting the possibility to target EPAC2 as a promising treatment modality for RSV.
First Evidence of Cryptic Species Diversity and Population Structuring of Selaroides leptolepis in the Tropical Western Pacific
Authors: Halasan Lorenzo C. , Geraldino Paul John L. , Lin Hsiu-Chin
Published: October 2021

The yellowstripe scad,Selaroides leptolepis(Carangidae), is an important fish commodity in the Tropical Western Pacific (TWP). It has a latitudinal Pacific range from south of Japan down to northern Australia, with the highest concentration in Southeast Asia. However, its TWP fishing grounds have long been a hotspot of unsustainable exploitations, thus threatening the remaining wild populations. Despite the species’ commercial significance, there is limited understanding of its genetic structure and diversity. Herein, the genetic structure ofS. leptolepiswas examined using mitochondrialCOIandCytBsequences. Both markers denoted significant genetic structuring based on high overall FSTvalues. Hierarchical analysis of molecular variance (AMOVA), maximum likelihood (ML) phylogenetic trees, and median-joining (MJ) haplotype networks strongly supported the occurrence of two allopatrically distributed lineages. These comprised of a widespread Asian lineage and an isolated Australian lineage. Within-lineage distances were low (K2P < 1%) whereas across-lineage distances were remarkably high (K2P > 6%), already comparable to that of interspecific carangid divergences. Haplotype sequence memberships, high genetic variations, and the geographic correlation suggested that the Australian lineage was a putative cryptic species. Historical demographic inferences also revealed that the species experienced rapid expansion commencing on the late Pleistocene, most likely during the end of the Last Glacial Maximum (∼20,000 years ago). The present study encouraged the application of lineage-specific management efforts, as the lineages are experiencing different evolutionary pressures. Overall, accurate knowledge of the species’ genetic distribution is fundamental in protecting its diversity and assuring stock sustainability.
A Nitric Oxide–Modulated Variable-Order Fractional Maxwell Viscoelastic Model of Cerebral Vascular Walls
Authors: Drapaca Corina S.
Published: October 2021

It is well known that the mechanical behavior of arterial walls plays an important role in the pathogenesis of vascular diseases. Most studies existing in the literature focus on the mechanical interactions between the blood flow and wall’s deformations. However, in the brain, the smaller vessels experience not only oscillatory forces due to the pulsatile blood flow but also structural and morphological changes controlled by the surrounding brain cells. In this study, the mechanical deformation of the cerebral arterial wall caused by the pulsatile blood flow and the dynamics of the neuronal nitric oxide (NO) is investigated. NO is a small diffusive gaseous molecule produced by the endothelial cells and neurons, which is involved in the regulation of cerebral blood flow and pressure. The cerebral vessel is assumed to be a hollow axial symmetric cylinder whose wall thickness is much smaller than the cylinder’s radius and longitudinal length is much less than the propagating wavelength. The wall is an isotropic, homogeneous linear viscoelastic material described by an NO-modulated variable-order fractional Maxwell model. A fractional telegraph equation is obtained for the axial component of the displacement. Patterns of wall’s deformation are investigated through numerical simulations. The results suggest that a significantly decreased inactivation of the neuronal NO may cause a reduction in the shear stress at the blood-vessel interface, which could lead to a decrease in the production of shear-induced endothelial NO and neurovascular disease.
Long-Term Retinal Neurovascular and Choroidal Changes After Panretinal Photocoagulation in Diabetic Retinopathy
Authors: Huang Tian , Li Xiaoli , Xie Jie , Zhang Liang , Zhang Guanrong , Zhang Aiping , Chen Xiangting , Cui Ying , Meng Qianli
Published: October 2021

Purpose: To evaluate the long-term retinal microvascular, neural, and choroidal changes in the patients with severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP).

Methods: Forty-five eyes of 28 patients with treatment-naive severe NPDR and PDR were included and followed for 12 months after PRP. Microvascular and neural changes in the macular and peripapillary areas were assessed by using optical coherence tomography angiography. Subfoveal choroidal thickness (SFCT) was measured by using optical coherence tomography. A Linear mixed-effects model was used to highlight the differences for the variables after adjusting for sex, age, and axial length.

Results: Compared to baseline, there were no statistical differences in the best corrected visual acuity (BCVA), macular and peripapillary vessel density (VD), and SFCT following PRP. Macular thickness significantly increased at 1 and 3–6 months after PRP (p < 0.05), while the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness significantly increased at 1 month postoperatively (p < 0.01). Global loss volume and focal loss volume significantly decreased at the same time point (p < 0.05).

Conclusion: The unchanged BCVA, VD, the thickness of RNFL and GCC, and SFCT during the 12-month follow-up period suggest that PRP may prevent the retinal neurovascular and choroidal damage.
Frequency-Dependent Effects on Coordination and Prefrontal Hemodynamics During Finger Force Production Tasks
Authors: Xu Dayuan , Shin Narae , Lee Sungjun , Park Jaebum
Published: October 2021

Behavioral stability partially depends on the variability of net outcomes by means of the co-varied adjustment of individual elements such as multi-finger forces. The properties of cyclic actions affect stability and variability of the performance as well as the activation of the prefrontal cortex that is an origin of subcortical structure for the coordinative actions. Little research has been done on the issue of the relationship between stability and neuronal response. The purpose of the study was to investigate the changes in the neural response, particularly at the prefrontal cortex, to the frequencies of isometric cyclic finger force production. The main experimental task was to produce finger forces while matching the produced force to sine-wave templates as accurately as possible. Also, the hemodynamics responses of the prefrontal cortex, including oxy-hemoglobin concentration (ΔHbO) and the functional connectivity, were measured using functional near-infrared spectroscopy. The frequency conditions comprised 0.1, 1, and 2 Hz. The uncontrolled manifold (UCM) approach was applied to compute synergy indices in time-series. The relative phase (RP), the coefficient of variation (CV) of the peak and trough force values were computed as the indices of performance accuracy. The statistical parametric mapping (SPM) was implemented to compare the synergy indices of three frequency conditions in time-series. A less accurate performance in the high-frequency condition was caused not by the RP, but mainly by the inconsistent peak force values (CV; p < 0.01, ηp2 = 0.90). The SPM analysis revealed that the synergy indices were larger in the low-frequency than in high-frequency conditions. Further, the ΔHbO remained unchanged under all frequency conditions, while the functional connectivity decreased with an increase in the frequency of cyclic force production. The current results suggested that the concurrent activation of the prefrontal region mainly depends on the frequency of cyclic force production, which was associated with the strength of stability indices and performance errors. The current study is the first work to uncover the effect of frequency on the multi-finger synergies as to the hemodynamic response in the prefrontal cortex, which possibly provides a clue of the neural mechanism of synergy formation and its changes.
Thalamostriatal System Controls the Acquisition, Performance, and Flexibility of Learning Behavior
Authors: Kato Shigeki , Nishizawa Kayo , Kobayashi Kazuto
Published: October 2021

The dorsal striatum (DS) is a key structure of the basal ganglia circuitry, which regulates various types of learning processes and flexible switching of behavior. Intralaminar thalamic nuclei (ILNs) provide the main source of thalamostriatal inputs to the DS and constitute multiple nuclear groups, each of which innervates specific subdivisions of the striatum. Although the anatomical and electrophysiological properties of thalamostriatal neurons have been previously characterized, the behavioral and physiological functions of these neurons remain unclarified. Two representative thalamostriatal cell groups in the parafascicular nucleus (PF) and the central lateral nucleus (CL) are located in the caudal and rostral regions of the ILNs in rodents. Recently, the behavioral roles of these thalamostriatal cell groups have been investigated by the use of genetic and pharmacological manipulation techniques. In the current review, we summarize behavioral studies on thalamostriatal neurons, showing the key roles of these neurons in different learning processes, such as the acquisition, performance, and flexibility of behavior.
Gum Arabic Edible Coating Reduces Postharvest Decay and Alleviates Nutritional Quality Deterioration of Ponkan Fruit During Cold Storage
Authors: Huang Qiang , Wan Chunpeng , Zhang Yajie , Chen Chuying , Chen Jinyin
Published: October 2021

The storability recession during storage limits the postharvest storage life of Ponkan (Citrus reticulata Blanco cv. Ponkan) fruit and its nutritional value, which potentially lead to huge losses. To develop an effective technique to reduce Ponkan fruit postharvest decay and to maintain the nutritional quality, the preservation effect of 9, 12, and 15% postharvest gum arabic (GA) coatings on Ponkan fruit was investigated. The 12 and 15% GA coatings effectively reduced fruit decay as well as weight loss, retained higher total soluble solids (TSS) content, suppressed titratable acidity (TA) degradation, and postponed the rise in ripening index (RI). Moreover, the 12% GA-coated fruit exhibited a lower respiration rate, electrical conductivity, and malondialdehyde (MDA) accumulation than the uncoated (control) fruit. The 12% GA coating treatment decreased the loss of ascorbic acid (AsA), total phenols, and total flavonoids and maintained higher amounts of non-enzymatic antioxidants. Furthermore, the 12% GA coating treatment increased antioxidant enzymes' activities as well as delayed the reduction of total antioxidant capacity (TAC). These results suggest that, with the cold storage increasing time, the 12% GA-coated fruit exhibited better postharvest storability and higher nutritional quality than the control fruit. The GA coating treatment could be used as a commercial wax to improve postharvest storability, extend its storage life, and maintain the nutritional value of Ponkan fruit up to 120 days of cold storage.
Non-destructive Detection of Insect Foreign Bodies in Finishing Tea Product Based on Terahertz Spectrum and Image
Authors: Sun Xudong , Li Jiajun , Shen Yun , Li Wenping
Published: October 2021

Non-destructive testing of low-density and organic foreign bodies is the main challenge for food safety control. Terahertz time-domain spectroscopy (THz-TDS) and imaging technologies were applied to explore the feasibility of detection for insect foreign bodies in the finishing tea products. THz-TDS of tea leaves and foreign bodies of insects demonstrated significant differences in terms of time domain and frequency signals in the range of 0.3–1.0 THz. These signals were corrected by the use of adaptive iteratively reweighted penalized least squares (AirPLS), asymmetric least squares (AsLS), and baseline estimation and de-noising using sparsity (BEADS) for reducing baseline drift and enhancing effective spectral information. The K-nearest neighbor (KNN) and partial least squares discrimination analysis (PLS-DA) models showed the best performance after AirPLS correction with the prediction accuracy of 98 and 100%, respectively. In addition, the locations and outlines of insect bodies could be clearly presented via the THz-TDS image. These results suggested that THz-TDS spectroscopy and imaging provide an alternative tool for the detection of insect foreign bodies in finishing tea products.
Gut Microbiota for Esophageal Cancer: Role in Carcinogenesis and Clinical Implications
Authors: Zhou Jianfeng , Sun Shangwei , Luan Siyuan , Xiao Xin , Yang Yushang , Mao Chengyi , Chen Longqi , Zeng Xiaoxi , Zhang Yonggang , Yuan Yong
Published: October 2021

Esophageal cancer (EC) is a common malignant tumor of the upper digestive tract. The microbiota in the digestive tract epithelium comprises a large number of microorganisms that adapt to the immune defense and interact with the host to form symbiotic networks, which affect many physiological processes such as metabolism, tissue development, and immune response. Reports indicate that there are microbial compositional changes in patients with EC, which provides an important opportunity to advance clinical applications based on findings on the gut microbiota. For example, microbiota detection can be used as a biomarker for screening and prognosis, and microorganism levels can be adjusted to treat cancer and decrease the adverse effects of treatment. This review aims to provide an outline of the gut microbiota in esophageal neoplasia, including the mechanisms involved in microbiota-related carcinogenesis and the prospect of utilizing the microbiota as EC biomarkers and treatment targets. These findings have important implications for translating the use of gut microbiota in clinical applications.
Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges
Authors: Zhang Wanru , An Yaping , Qin Xiali , Wu Xuemei , Wang Xinyu , Hou Huiqin , Song Xueli , Liu Tianyu , Wang Bangmao , Huang Xuan , Cao Hailong
Published: October 2021

Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.
ARV-825 Demonstrates Antitumor Activity in Gastric Cancer via MYC-Targets and G2M-Checkpoint Signaling Pathways
Authors: Liao Xinmei , Qian Xiaoqing , Zhang Zimu , Tao Yanfang , Li Zhiheng , Zhang Qian , Liang Hui , Li Xiaolu , Xie Yi , Zhuo Ran , Chen Yanling , Jiang You , Cao Haibo , Niu Jiaqi , Xue Cuili , Ni Jian , Pan Jian , Cui Daxiang
Published: October 2021

Objective

Suppression of bromodomain and extra terminal (BET) proteins has a bright prospect to treat MYC-driven tumors. Bromodomain containing 4 (BRD4) is one of the BET proteins. ARV-825, consisting of a BRD4 inhibitor conjugated with a cereblon ligand using proteolysis-targeting chimera (PROTAC) technology, was proven to decrease the tumor growth effectively and continuously. Nevertheless, the efficacy and mechanisms of ARV-825 in gastric cancer are still poorly understood.

Methods

Cell counting kit 8 assay, lentivirus infection, Western blotting analysis, Annexin V/propidium iodide (PI) staining, RNA sequencing, a xenograft model, and immunohistochemistry were used to assess the efficacy of ARV-825 in cell level and animal model.

Results

The messenger RNA (mRNA) expression of BRD4 in gastric cancer raised significantly than those in normal tissues, which suggested poor outcome of patients with gastric cancer. ARV-825 displayed higher anticancer efficiency in gastric cancer cells than OTX015 and JQ1. ARV-825 could inhibit cell growth, inducing cell cycle block and apoptosis in vitro. ARV-825 induced degradation of BRD4, BRD2, BRD3, c-MYC, and polo-like kinase 1 (PLK1) proteins in four gastric cancer cell lines. In addition, cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP) was elevated. Knockdown or overexpression CRBN could increase or decrease, respectively, the ARV-825 IC50 of gastric cancer cells. ARV-825 reduced MYC and PLK1 expression in gastric cancer cells. ARV-825 treatment significantly reduced tumor growth without toxic side effects and downregulated the expression of BRD4 in vivo.

Conclusions

High mRNA expression of BRD4 in gastric cancer indicated poor prognosis. ARV-825, a BRD4 inhibitor, could effectively suppress the growth and elevate the apoptosis of gastric cancer cells via transcription downregulation of c-MYC and PLK1. These results implied that ARV-825 could be a good therapeutic strategy to treat gastric cancer.
Initial Incomplete Thermal Ablation Is Associated With a High Risk of Tumor Progression in Patients With Hepatocellular Carcinoma
Authors: Tan Jie , Tang Tian , Zhao Wei , Zhang Zi-Shu , Xiao Yu-Dong
Published: October 2021

Purpose

To investigate whether incomplete thermal ablation is associated with a high risk of tumor progression in patients with hepatocellular carcinoma (HCC), and to compare the efficacy of repeated thermal ablation and transarterial chemoembolization (TACE) for residual tumor after incomplete ablation.

Methods

This retrospective study included 284 patients with unresectable HCC who underwent thermal ablation from June 2014 to September 2020. The response of the initially attempted ablation was classified into complete (n=236) and incomplete (n=48). The progression-free survival (PFS) and overall survival (OS) were compared between patients with complete and incomplete responses, before and after a one-to-one propensity score-matching (PSM), and between patients in whom repeated ablation or TACE was performed after a first attempt incomplete ablation.

Results

After PSM of the 284 patients, 46 pairs of patients were matched. The PFS was significantly higher in the complete response group than in the incomplete response group (P<0.001). No difference in OS was noted between two groups (P=0.181). After a first attempt incomplete ablation, 29 and 19 patients underwent repeated ablation and TACE, respectively. There were no significant differences in PFS (P=0.424) and OS (P=0.178) between patients who underwent repeated ablation and TACE. In multivariate Cox regression analysis, incomplete response (P<0.001) and Child-Pugh class B (P=0.017) were independent risk factors for tumor progression, while higher AFP level (P=0.011) and Child-Pugh class B (P=0.026) were independent risk factors for poor OS.

Conclusion

Although patients with incomplete ablation are associated with tumor progression compared with those with complete ablation, their OS is not affected by incomplete ablation. When patients present with residual tumors, TACE may be an alternative if repeated ablation is infeasible.
BuqiTongluo Granule for Ischemic Stroke, Stable Angina Pectoris, Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis Syndrome: Rationale and Novel Basket Design
Authors: Liu Weidi , Zhou Li , Feng Luda , Zhang Dandan , Zhang Chi , Gao Ying ,   behalf of the BOSS Group
Published: October 2021

Background: BuqiTongluo (BQTL) granules are herbal phenotypic drugs for Qi deficiency and blood stasis (QDBS) syndrome. Its discovery relied primarily on knowledge of observable phenotypic changes associated with diseases. Although BQTL granules have been widely advocated by Chinese Medicine (CM) practitioners, its use lacks empirical support.

Aim of the study: In this basket trial, the efficacy of BQTL granules in multiple diseases that have the QDBS syndrome in common will be compared with placebo.

Materials and Methods: The BuqiTongluo granule for Qi deficiency and blood stasis syndrome (BOSS) study is a basket herbal trial (ClinicalTrials.gov, NCT04408261). It will be a double-blinded, randomized, placebo-controlled, parallel, multicenter, clinical trial. In total, 432 patients (1:1:1 ischemic stroke, stable angina pectoris, and diabetic peripheral neuropathy), who meet the operationalized diagnostic criteria for QDBS syndrome, have been recruited and randomized in a ratio of 1:1 to receive 6 weeks’ treatment with BQTL granules or placebo. The primary outcome is the change in the QDBS syndrome score at week 6 from baseline. Secondary outcomes include objective outcome measures for the three diseases and adverse events. Omics will help to understand these responses by molecular events.

Conclusion: QDBS syndrome is a common phenotypic marker that was hypothesized to predict whether patients with multiple diseases would respond to this targeted therapy. No previous basket trial has assessed the potential efficacy of an herbal intervention for multiple diseases. The unique promise of the trial is its ability to exploit a disease phenotype to discover novel treatments for three diseases for which the root cause is unknown, complex, or multifactorial, and for which scientific understanding is insufficient to provide valid molecular targets.
Dissecting the Roles of the Autonomic Nervous System and Physical Activity on Circadian Heart Rate Fluctuations in Mice
Authors: Barazi Nour , Polidovitch Nazari , Debi Ryan , Yakobov Simona , Lakin Robert , Backx Peter H.
Published: October 2021

Heart rate (HR) and blood pressure as well as adverse cardiovascular events show clear circadian patterns, which are linked to interdependent daily variations in physical activity and cardiac autonomic nerve system (ANS) activity. We set out to assess the relative contributions of the ANS (alone) and physical activity to circadian HR fluctuations. To do so, we measured HR (beats per minute, bpm) in mice that were either immobilized using isoflurane anesthesia or free-moving. Nonlinear fits of HR data to sine functions revealed that anesthetized mice display brisk circadian HR fluctuations with amplitudes of 47.1±7.4bpm with the highest HRs in middle of the dark (active) period (ZT 18: 589±46bpm) and lowest HRs in the middle of the light (rest) period (ZT 6: 497±54bpm). The circadian HR fluctuations were reduced by ~70% following blockade of cardiac parasympathetic nervous activity (PNA) with atropine while declining by <15% following cardiac sympathetic nerve activity (SNA) blockade with propranolol. Small HR fluctuation amplitudes (11.6±5.9bpm) remained after complete cardiac ANS blockade. Remarkably, circadian HR fluctuation amplitudes in freely moving, telemetrized mice were only ~32% larger than in anesthetized mice. However, after gaining access to running wheels for 1week, circadian HR fluctuations increase to 102.9±12.1bpm and this is linked directly to increased O2 consumption during running. We conclude that, independent of physical activity, the ANS is a major determinant of circadian HR variations with PNA playing a dominant role compared to SNA. The effects of physical activity to the daily HR variations are remarkably small unless mice get access to running wheels.
The Disturbing Effect of Neuromuscular Fatigue on Postural Control Is Accentuated in the Premenstrual Phase in Female Athletes
Authors: Kacem Maissa , Borji Rihab , Sahli Sonia , Rebai Haithem
Published: October 2021

This study explored the fatigue effect on postural control (PC) across menstrual cycle phases (MCPs) in female athletes. Isometric maximal voluntary contraction (IMVC), the center of pressure sway area (CoParea), CoP length in the medio-lateral (CoPLX) and antero-posterior (CoPLY) directions, and Y-balance test (YBT) were assessed before and after a fatiguing exercise during the follicular phase (FP), mid-luteal phase (LP), and premenstrual phase (PMP). Baseline normalized reach distances (NRDs) for the YBT were lower (p = 0.00) in the PMP compared to others MCPs, but the IMVC, CoParea, CoPLX, and CoPLY remained unchanged. After exercise, the IMVC and the NRD decrease was higher at PMP compared to FP (p = 0.00) and LP (p = 0.00). The CoParea, CoPLX, and CoPLY increase was higher in the PMP compared to FP (p = 0.00) and LP (p = 0.00). It was concluded that there is an accentuated PC impairment after exercise observed at PMP.
Next Generation dsRNA-Based Insect Control: Success So Far and Challenges
Authors: Nitnavare Rahul B. , Bhattacharya Joorie , Singh Satnam , Kour Amardeep , Hawkesford Malcolm J. , Arora Naveen
Published: October 2021

RNA interference (RNAi) is a method of gene silencing where dsRNA is digested into small interfering RNA (siRNA) in the presence of enzymes. These siRNAs then target homologous mRNA sequences aided by the RNA-induced silencing complex (RISC). The mechanism of dsRNA uptake has been well studied and established across many living organisms including insects. In insects, RNAi is a novel and potential tool to develop future pest management means targeting various classes of insects including dipterans, coleopterans, hemipterans, lepidopterans, hymenopterans and isopterans. However, the extent of RNAi in individual class varies due to underlying mechanisms. The present review focuses on three major insect classes viz hemipterans, lepidopterans and coleopterans and the rationale behind this lies in the fact that studies pertaining to RNAi has been extensively performed in these groups. Additionally, these classes harbour major agriculturally important pest species which require due attention. Interestingly, all the three classes exhibit varying levels of RNAi efficiencies with the coleopterans exhibiting maximum response, while hemipterans are relatively inefficient. Lepidopterans on the other hand, show minimum response to RNAi. This has been attributed to many facts and few important being endosomal escape, high activity dsRNA-specific nucleases, and highly alkaline gut environment which renders the dsRNA unstable. Various methods have been established to ensure safe delivery of dsRNA into the biological system of the insect. The most common method for dsRNA administration is supplementing the diet of insects via spraying onto leaves and other commonly eaten parts of the plant. This method is environment-friendly and superior to the hazardous effects of pesticides. Another method involves submergence of root systems in dsRNA solutions and subsequent uptake by the phloem. Additionally, more recent techniques are nanoparticle- and Agrobacterium-mediated delivery systems. However, due to the novelty of these biotechnological methods and recalcitrant nature of certain crops, further optimization is required. This review emphasizes on RNAi developments in agriculturally important insect species and the major hurdles for efficient RNAi in these groups. The review also discusses in detail the development of new techniques to enhance RNAi efficiency using liposomes and nanoparticles, transplastomics, microbial-mediated delivery and chemical methods.
The Relation Between Television Viewing Time and Reading Achievement in Elementary School Children: A Test of Substitution and Inhibition Hypotheses
Authors: Supper Wilfried , Guay Frédéric , Talbot Denis
Published: October 2021

Research has focused on the relations between television (TV) viewing time and children’s reading achievement. Two hypotheses have been proposed to explain this relation. The substitution hypothesis proposes that TV viewing distracts students from activities that are important for their learning. The inhibition hypothesis proposes that watching television inhibits important affective/cognitive skills. In this study, we test both hypotheses by estimating the relation between TV viewing time and reading achievement. We use the frequency of students’ leisure reading and the frequency of interactions between students and their parents as potential mediators to test the substitution hypothesis, whereas for the inhibition one, we use students’ intrinsic motivation to read and their level of inattention. Data come from the Québec Longitudinal Study of Child Development (QLSCD). Designed by the Institut de la statistique du Québec, QLSCD covers a wide range of themes. The QLSCD is representative of children in Québec and contains 2223 participants who were followed from 0 to 21 years old. The four structural models tested are built as follows: the TV viewing time at 6 years old predicts the four mediating variables at 8 years old, which in turn predicts reading achievement at 10 years old. In addition, we have tested models’ gender invariance. Results indicate that TV viewing time is not directly or indirectly associated with reading achievement. Specifically, it is not associated with the mediating variables of child-parent interactions, intrinsic motivation, and inattention. However, the frequency of leisure reading is negatively associated with the time spent watching TV. This association is very small (−0.07) and has no indirect effect on reading achievement. Finally, results do not vary according to the gender of the participants. Our results are in line with those of previous studies in the field and cast some doubts on the potential negative effects of TV viewing time on reading achievement.
Does Creativity Influence Visual Perception? - An Event-Related Potential Study With Younger and Older Adults
Authors: Csizmadia Petra , Czigler István , Nagy Boglárka , Gaál Zsófia Anna
Published: October 2021

We do not know enough about the cognitive background of creativity despite its significance. Using an active oddball paradigm with unambiguous and ambiguous portrait paintings as the standard stimuli, our aim was to examine whether: creativity in the figural domain influences the perception of visual stimuli; any stages of visual processing; or if healthy aging has an effect on these processes. We investigated event related potentials (ERPs) and applied ERP decoding analyses in four groups: younger less creative; younger creative; older less creative; and older creative adults. The early visual processing did not differ between creativity groups. In the later ERP stages the amplitude for the creative compared with the less creative groups was larger between 300 and 500 ms. The stimuli types were clearly distinguishable: within the 300–500 ms range the amplitude was larger for ambiguous rather than unambiguous paintings, but this difference in the traditional ERP analysis was only observable in the younger, not elderly groups, who also had this difference when using decoding analysis. Our results could not prove that visual creativity influences the early stage of perception, but showed creativity had an effect on stimulus processing in the 300–500 ms range, in indexing differences in top-down control, and having more flexible cognitive control in the younger creative group.
EFL Teachers' Optimism and Commitment and Their Contribution to Students' Academic Success
Authors: Lu Di
Published: October 2021

The present review study determines to scrutinize EFL teachers' optimism and commitment and their contribution to students' academic success. Academic optimism, as a new construct, is evolving from the examination of the positive psychology (PP), societal principal, and communal school assets that affect the attainment and success of all learners. In addition, within the past decades, commitment has received a great level of consideration, principally in the domain of structural research. The straightforward perseverance of this review is to extend the concept of academic optimism to individuals, that is, to hypothesize theoretical optimism and approve the efficacy of this paradigm at the instructor level in relation to students' academic success. According to the literature review, the definitions of these constructs, namely teachers' optimism and commitment, and students' academic success, as well as empirical studies in this domain are presented. As a conclusion, this study, to some extent, promotes the educators' mindfulness about their commitment. In this respect, pedagogical implications for teachers, school principals, teacher-trainers, and future researchers are presented, and new guidelines for further research are determined.
Psychiatric Comorbidity and Economic Hardship as Risk Factors for Intentional Self-Harm in Gambling Disorder—A Nationwide Register Study
Authors: Karlsson Anna , Hedén Olivia , Hansson Helena , Sandgren Jenny , Håkansson Anders
Published: October 2021

Background: There is an increased risk of suicidality in gambling disorder (GD) and economic hardship is common in the population. Economic hardship itself is a risk factor for suicidality. This study aims to explore the risk of intentional self-harm in GD utilizing social welfare payment (SWP) as a proxy for economic hardship and exploring how economic hardship, gender, criminality, socioeconomic-, and psychiatric risk factors might contribute to intentional self-harm in GD.

Methods: This is a nationwide register-based study of 848 individuals diagnosed with GD in the Swedish healthcare system during the years of 2011–2014 with an average follow up of 4.9 years. Pearson's Chi-square analyses were carried out for comparisons regarding psychiatric comorbidity and intentional self-harm with regards to gender and SWPs. Univariable and multivariable Cox regression were utilized to analyse risk factors for intentional self-harm.

Results: A large part of the study population received SWPs (45.5% with an insignificant overrepresentation of women) and psychiatric disorders were more common in these individuals (p < 0.001). Conviction for crime in general (p < 0.001) as well as intentional self-harm (p = 0.025) were also more common amongst recipients of SWPs. Criminal conviction in general was abundant (26.5%). In the stepwise multivariable regression, substance-related diagnoses as well as anxiety, depressive, and personality disorders remained risk factors for intentional self-harm and no significant results were found with regards to gender, criminal history, or SWPs.

Conclusions: Social welfare payment was common among GD patients and intentional self-harm was more common amongst recipients than GD patients as a whole. Social welfare payments were however not a significant risk factor for intentional self-harm. However, attention to suicidality and self-injurious behavior should be paid from social services controlling SWPs due to the large prevalence of intentional self-harm in this group. In accordance with previous studies, comorbid psychiatric disorders such as anxiety, depression, substance use, and personality disorders increased the risk of intentional self-harm.
Antianhedonic Effect of Repeated Ketamine Infusions in Patients With Treatment Resistant Depression
Authors: Wilkowska Alina , Wiglusz Mariusz Stanisław , Gałuszko-Wegielnik Maria , Włodarczyk Adam , Cubała Wiesław Jerzy
Published: October 2021

Anhedonia constitutes one of the main symptoms of depressive episode. It correlates with suicidality and significantly effects the quality of patient's lives. Available treatments are not sufficient against this group of symptoms. Ketamine is a novel, rapid acting strategy for treatment resistant depression. Here we report the change in symptoms of anhedonia measured by Snaith-Hamilton Pleasure Scale as an effect of eight ketamine infusions as an add-on treatment in 42 patients with treatment resistant depression. We also determined the effect of this change on the severity of depressive symptoms measured by Inventory for Depression Symptomatology-Self Report 30-Item (IDS-SR 30). We have observed statistically significant decrease in the level of anhedonia during ketamine treatment. After adjusting for potential confounders we have found that significant reduction in Snaith-Hamilton Pleasure Scale (SHAPS) after each infusion and 1 week post treatment was observed only among patients who did not use benzodiazepines. The reduction in symptoms of anhedonia mediates the antidepressive effect of ketamine. The results need replication in a larger randomized placebo controlled trial.