bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Dewaterability of Waste Activated Sludge by Fe(II)-Activated Potassium Periodate Oxidation
Authors: Xiao Hong , Liu Qing , Wang Yingjun , Zhu Ying , Fang Dexin , Wu Ganxue , Zeng Zhenxing , Peng Hong
Published: November 2022

Fe(II)-activated potassium periodate (KIO4) oxidation was used to improve the dewaterability of waste-activated sludge for the first time. Compared with those of raw sludge, the capillary suction time (CST), specific resistance filtration (SRF), and water content of filter cake (WC) of sludge treated using the Fe(II)/KIO4 process under the optimal conditions (i.e., the initial pH = 6.8, KIO4 dose = 1.4 mmol/g volatile suspended solids, Fe(II)/KIO4 molar ratio = 1.2) decreased by 64.34%, 84.13%, and 6.69%, respectively. For conditioned sludge flocs, the Zeta potential and particle size were increased, and hydrophilic proteins in extracellular polymeric substances (EPS) were partly degraded, accompanied by the transformation of tightly bound EPS into soluble EPS and the conversion of dense sludge flocs into loose and porous ones. During Fe(II)/KIO4 oxidation, Fe(IV) and the accompanying •OH were determined as the predominant reactive species and the underlying mechanism of sludge EPS degradation was proposed. This work provides a prospective method for conditioning the sludge dewaterability.
China’s Accession to the WTO as a Shock to Residents’ Health—A Difference-in-Difference Approach
Authors: Sun Yiping , Wu Chengjun , Zhu Xiaoming , Bian Pingguan
Published: November 2022

The impact of regional trade shocks on population health has been a topic of interest in health economics in recent years. Unfortunately, there are few studies directly discussing the impact of regional trade shocks caused by China’s WTO accession on the health of Chinese residents, which is essential to explore the connection between a country´s opening to international trade and the health of its residents. Taking China’s accession to the WTO as a quasi-natural experiment, based on the micro individual samples of the China Health and Nutrition Survey (CHNS) from 1993 to 2011, this paper, for the first time, studies the impact of regional tariff uncertainty caused by China’s accession to the WTO on the health of Chinese residents and its mechanisms by adopting the Difference-in-Difference (DID) model. The study finds that compared with the areas initially facing low tariff uncertainty, the areas with high initial tariff uncertainty have a greater negative impact on the health of residents after China acceded to WTO, which means that the trade shock caused damage to the health of residents. After a series of tests on the effectiveness and robustness of DID, this conclusion is still valid. The impact of the trade shock on residents’ health varies with the type of residence, gender, and geographical location, and there is a nonlinear relationship. Further mechanism tests show that the trade shock has worsened the health status of residents through rural migration channels, working hours channels, and pollution emission channels. This study provides micro evidence for objectively evaluating the health effects of trade shock and has important implication for considering the health loss of Chinese residents in the process of trade liberalization.
High Serum Levels of IL-6 Are Associated with Suicide Attempt but Not with High Lethality Suicide Attempts: A Preliminary Case–Control Study
Authors: Castillo-Avila Rosa Giannina , Genis-Mendoza Alma Delia , Juárez-Rojop Isela Esther , López-Narváez María Lilia , Dionisio-García Diana María , Nolasco-Rosales Germán Alberto , Ramos-Méndez Miguel Ángel , Hernández-Díaz Yazmín , Tovilla-Zárate Carlos Alfonso , González-Castro Thelma Beatriz , Nicolini Humberto
Published: November 2022

Suicide attempts are an emerging health problem around the world. Increased levels of IL-6 have been associated with suicidal behavior. Therefore, the aims of this study were to evaluate the serum levels of IL-6 in individuals with suicide attempts and a comparison group and to associate the IL-6 levels with the lethality of the suicide attempt. Additionally, we associated the rs2228145 polymorphism of the IL6R gene with suicide attempts or with the IL-6 serum levels. Suicide attempts and their lethality were evaluated using the Columbia Suicide Severity Rating Scale. The serum concentrations of IL-6 were measured by the ELISA technique in individuals with suicide attempts and then compared to a control group. The rs2228145 polymorphism of the IL6R gene was analyzed by real-time polymerase chain reaction. We found elevated serum levels of IL-6 in the suicide attempt group when compared to the control group (F = 10.37, p = 0.002). However, we found no differences of the IL-6 levels between high and low lethality. The IL6R gene polymorphism rs2479409 was not associated with suicide attempts. Our data suggest that IL-6 serum is increased in individuals with suicide attempts.
The Potential Impact of COVID-19 on Health-Related Quality of Life in Children and Adolescents: A Systematic Review
Authors: Ahn Si Nae
Published: November 2022

This was a systematic review of studies examining the effect of COVID-19 on the health-related quality of life (HRQoL) of children and adolescents. The review was conducted by examining the current literature and analyzing up-to-date evidence. The studies were extracted from three major databases (CINAHL Complete, MEDLINE, and Web of Science) and analyzed. Studies on children and adolescents whose HRQoL has been affected by COVID-19 were included based on the eligibility criteria. Ultimately, eight studies met these criteria. The evidence of the selected studies was analyzed; the research design, age categories, respondents, evaluation tools, gender differences, and variability before and during COVID-19 were systematically reviewed. This review found differences in these groups regarding oral symptoms, functional limitations, emotional well-being, and social well-being. Furthermore, this review highlighted the relative paucity of studies that comprehensively investigate the latest evidence of changes in the HRQoL of children and adolescents due to COVID-19 in preparation for the post-COVID era.
Supply–Demand Evaluation of Green Stormwater Infrastructure (GSI) Based on the Model of Coupling Coordination
Authors: Wang Mo , Chen Furong , Zhang Dongqing , Rao Qiuyi , Li Jianjun , Tan Soon Keat
Published: November 2022

The rational spatial allocation of Green Stormwater Infrastructure (GSI), which is an alternative land development approach for managing stormwater close to the source, exerts a crucial effect on coordinating urban development and hydrological sustainability. The balance between the supply and demand of urban facilities has been an influential standard for determining the rationality of this allocation. However, at this stage, research on evaluating planning from the perspective of supply–demand in GSI is still limited. This study proposed an evaluation method for assessing supply–demand levels in GSIs in Guangzhou, China, using the coupling coordination model consisting of Coupling Degree (CD) and Coupling Coordination Degree (CCD). Furthermore, the spatial distributions of supply–demand balance and resource mismatch were identified. The results indicated that the supply and demand levels of GSI exhibited significant spatial differences in distribution, with most streets being in short supply. The GSI exhibited a high CD value of 0.575 and a poor CCD value of 0.328, implying a significant imbalance in facility allocation. A lot of newly planned facilities failed to effectively cover the streets in need of improvement, so it became essential to adjust the planning scheme. The findings of this study can facilitate the decision-makers in assessing the supply–demand levels in GSI and provide a reference of facility allocation for the sustainable construction of Sponge City.
Feasibility of an Upper Limb Strength Training Program in Persons with Spinal Cord Injury during Primary Rehabilitation—An Uncontrolled Interventional Study
Authors: Perret Claudio , De Jaegher Jolien , Velstra Inge-Marie
Published: November 2022

Data concerning the outcomes of standardized strength-training programs in people with acute spinal cord injury (SCI) are scarce. The present study evaluated the feasibility and effects of a clinic-internal strength-training concept in people with paraplegia during the course of primary rehabilitation. For this purpose, participants followed a 10–12 week standardized supervised strength-training program (30 training sessions) during primary rehabilitation. At the beginning, 5–6 weeks and 10–12 weeks later, maximal strength based on indirect one-repetition maximum (1RM) measurements for two specific exercises (triceps press; horizontal rowing pull) was determined. Twelve out of 17 participants successfully completed the study. Maximal weights for 1RM significantly increased over the 10–12 week training program for the triceps press (+30%; p = 0.018) and the horizontal rowing pull (+41%; p = 0.008). Training compliance was 95%. Reasons for study exclusion were urgent surgery (n = 2), cardio-respiratory complications (n = 1), shoulder pain (n = 1) and a training compliance of less than 50% (n = 1). In conclusion, a supervised and standardized strength-training program during primary rehabilitation of people with paraplegia is feasible and leads to significant increases in maximal strength. Although study participants showed a high training compliance, factors such as medical complications may impede the proper implementation of a strength-training concept into daily clinical practice.
The Guarantee Mechanism of China’s Environmental Protection Strategy from the Perspective of Global Environmental Governance—Focusing on the Punishment of Environmental Pollution Crime in China
Authors: An Ran , Sang Tian
Published: November 2022

Effective global environmental governance is the only viable way to solve the human environmental crisis. For a long time, China has been an active promoter and contributor to the global environmental governance system. In recent years, China has enhanced the penalty intensity of environmental crimes, the environmental pollution crimes in particular, and received good results in order to better realize the construction of ecological civilization and better fulfill the emission reduction targets of international environmental treaties. The deterioration of China’s environmental crisis in the past and the lack of deterrent effect of China’s environmental laws are closely related to the ineffective punishment of environmental crimes. In order to better promote environmental protection careers, China’s environmental crimes still need to be continuously optimized in terms of adding charges, legislative models and restorative justice.
The Effect of Iron Content on the Ammonia Selective Catalytic Reduction Reaction (NH3-SCR) Catalytic Performance of FeOx/SAPO-34
Authors: Li Zhaoyang , Chen Geng , Shao Zhenghua , Zhang Haonan , Guo Xiujuan
Published: November 2022

Iron-based catalysts are regarded as promising candidates for the ammonia selective catalytic reduction reaction (NH3-SCR) which show good catalytic activity at medium and high temperatures, whereas SAPO-34 molecular sieves have a micro-pore structure and are ideal catalyst carriers. In this paper, four FeOx/SAPO-34 molecular sieve catalysts with different iron contents (Fe = 1%, 2%, 3%, 4%) were prepared using an impregnation method. The effect of iron content on the surface properties and catalytic activity was investigated by a series of characterization techniques including XRD, SEM, BET, XPS, H2-TPR and NH3-TPD. Iron species in the FeOx/SAPO-34 catalysts exist in the form of isolated iron ions or well-dispersed small crystals and iron oxide species clusters. With the addition of iron content, the integrity of CHA (chabazite) zeolite structure remained, but the crystallinity was affected. The FeOx/SAPO-34 catalyst with 3% Fe loading showed a relatively flat surface with no large-diameter particles and strong oxidation-reduction ability. Meanwhile, more acidic sites are exposed, which accelerated the process of catalytic reaction. Thus, the FeOx/SAPO-34 catalyst with 3% Fe showed the best NO conversion performance among the four catalysts prepared and maintained more than 90% NO conversion efficiency in a wide temperature range from 310 °C to 450 °C.
Relationship between Physical Fitness and Academic Performance in University Students
Authors: Redondo-Flórez Laura , Ramos-Campo Domingo Jesús , Clemente-Suárez Vicente Javier
Published: November 2022

Several studies involving students have been developed with the objective to analyse the influence of different factors on academic performance. Nevertheless, all these studies were focused on stress and sympathetic modulation response instead of contemplating other physiological parameters that may affect academic performance. The aim of the present study was to analyse body composition, cardiovascular, sleep habits and physical activity factors related to the academic performance of university students. Two hundred and sixty-one students with bachelor’s degrees in physical activity and sports science participated in the present study (age: 22.49 ± 3.84 years; weight: 73.94 ± 11.4 kg; height: 176.28 ± 7.68 cm; 87.7% males). Participants were divided into two groups according to their academic performance: low academic performance group (LAPG) and high academic performance group (HAPG). Body composition, blood pressure, physical activity and sleep habits were measured, and maximum oxygen uptake was estimated by the Cooper’s 12 min run test. The results show that students with a high academic performance presented a higher VO2 max than the LAPG (LAPG = 40.32 ± 6.07; HAPG = 47.91 ± 6.89 mL/kg/min; p < 0.001), as well as lower diastolic blood pressure (LAPG = 72.44 ± 14.27; HAPG = 67.48 ± 13.50 mmHg; p < 0.01) and insomnia levels caused by breathing problems (LAPG = 0.37 ± 0.8; HAPG = 0.13 ± 0.42 a.u.; p = 0.046). Therefore, we found a relevant association between academic performance and VO2 max, diastolic blood pressure, and insomnia caused by breathing problems. These results highlight the importance of applying different programmes that may improve these factors, especially those related to physical activity and sleep habits in order to improve academic achievement.
Preliminary Study on the Distribution, Source, and Ecological Risk of Typical Microplastics in Karst Groundwater in Guizhou Province, China
Authors: An Xianjin , Li Wei , Lan Jiacheng , Adnan Muhammad
Published: November 2022

Karst groundwater is one of the important drinking water sources in karst areas, and it has an important role in maintaining the regional ecosystem and human health. The study of microplastics (MPs) in karst groundwater has rarely been reported, and the occurrence and migration behavior of MPs under the unique environmental conditions of karst is unclear. This study selected cave groundwater and common MPs in karst areas to explore the occurrence characteristics of MPs in groundwater to clarify the factors affecting the distribution and migration of MPs. The results showed that the abundance of MPs in karst groundwater was between 2.33 and 9.50 items·L−1, with an average abundance of 4.50 items·L−1. The microplastic size, type, color, and chemical composition were primarily 1~5 mm, film and fiber, color and transparent, and PS and PE, respectively. The risk characterization ratio (RCR) index results indicated that 80% of the samples were at a low ecological risk level, whereas 60% of the sampling points after concentrated rainfall in June were a medium ecological risk. The study showed that rainfall events significantly changed the abundance and migration of MPs in karst groundwater. The Pearson analysis showed a positive correlation between microplastic distribution and suspended particles (SP), total organic carbon (TOC), and water velocity (WV) in water. The study indicated that strong soil erosion in karst areas may also be one of the main sources of MPs in karst groundwater, and that karst groundwater microplastic pollution is an environmental problem that should not be ignored.
Conciseness, Financial Disclosure, and Market Reaction: A Textual Analysis of Annual Reports in Listed Chinese Companies
Authors: Alduais Fahd , Ali Almasria Nashat , Samara Abeer , Masadeh Ali
Published: November 2022

The purpose of this study was to examine the relationship between the conciseness and complexity of financial disclosures and market reactions, using the annual reports of Chinese-listed B-share companies over the period 2006–2018. We employed a set of statistical methods that were derived from other fields, such as computational and event studies, in order to derive the English annual reports of Chinese-listed companies, as well as to obtain other key financial indicators from the CSMAR database. Markets react significantly to increased report length, which means that managers that present poor returns with manipulated financial reports could be hiding poor returns. Additionally, the findings of this study are robust to additional tests that use alternative proxies. Furthermore, the results of this paper reinforce the hypothesis that the readability of financial reports affects financial market response. The results indicate that more complex financial reports are correlated with lower current returns, and negatively affect the expectations of future returns. For the purposes of avoiding the effects of the coronavirus pandemic on the results, we utilized data up to 2018. In light of this circumstance, we recommend that future research be conducted that compares results from before and after the coronavirus pandemic. The findings of our study have important implications for regulators, managers, and investors. Investors should obtain relevant information through annual reports; therefore, the importance of style is less relevant. Managers should be encouraged to write their annual reports more concisely. This study concluded that these reports are significant outputs of firms, and are widely read by investors. The study also provides empirical evidence of market reactions that are associated with readability and earnings, as well as with surprise earnings; thus, the complexity of annual reports provided by a variety of investors, using computational and event analysis, should be reduced.
Construction of a COVID-19 Pandemic Situation Knowledge Graph Considering Spatial Relationships: A Case Study of Guangzhou, China
Authors: Yang Xiaorui , Li Weihong , Chen Yebin , Guo Yunjian
Published: November 2022

The outbreak of COVID-19 (coronavirus disease 2019) has generated a large amount of spatiotemporal data. Using a knowledge graph can help to analyze the transmission relationship between cases and locate the transmission path of the pandemic, but researchers have paid little attention to the spatial relationships between geographical entities related to the pandemic. Therefore, we propose a method for constructing a pandemic situation knowledge graph of COVID-19 that considers spatial relationships. First, we created an ontology design of the pandemic data in which spatial relationships are considered. We then constructed a non-spatial relationships extraction model based on BERT and a spatial relationships extraction model based on spatial analysis theory. Second, taking the pandemic and geographic data of Guangzhou as an example, we modeled a pandemic corpus. We extracted entities and relationships based on this model, and we constructed a pandemic situation knowledge graph that considers spatial relationships. Finally, we verified the feasibility of using this method as a visualization exploratory tool in the analysis of spatial characteristics, pandemic development situation, case sources, and case relationships analysis of pandemic-related areas.
A Shape-Preserving Simplification Method for Urban Building Models
Authors: Xiang Hanyu , Huang Xianfeng , Lan Feng , Yang Chong , Gao Yunlong , Wu Wenyu , Zhang Fan
Published: November 2022

With the expansion of model scale and the improvement of model accuracy, the real-time rendering and displaying of 3D mesh models remain infeasible. To relieve such pressure, mesh simplification methods have been proposed to reduce the structural complexity while preserving the appearance. This work introduces a shape-preserving simplification method for urban building models. Compared to traditional simplification methods that only consider preserving local geometric features, we also consider the overall shapes of building models to avoid collapse with an increased simplification rate. The proposed method works in four steps. First, we filter mesh models to yield planar structures while preserving sharp features. Second, we detect the shapes of planar regions. Third, we simplify the planar and non-planar regions constrained by the overall shapes and local geometric features. Finally, we remap the texture. Experiments show the effectiveness of this method by evaluating it on various building models and comparing its performance with the original QEM algorithms. Furthermore, we maintain better spatial consistency in building models with different levels of detail (LOD) than traditional methods.
An Evaluation of Urban Renewal Based on Inclusive Development Theory: The Case of Wuhan, China
Authors: Liu Wei , Yang Jie , Gong Yue , Cheng Qi
Published: November 2022

After decades of development, China’s urban renewal is facing the problems of inequality and intolerance, neglecting vulnerable groups and triggering gentrification. These problems are rarely quantified and draw limited public concerns. To promote an inclusive urban development, we proposed a framework for the inclusive evaluation of urban renewal spaces, thus increasing the understanding of inclusive urban renewal. An evaluation method based on the theory of inclusive development was proposed, and it includes two steps. First, the evaluation index system of inclusive development at the community scale was created, including 24 indicators from five aspects: cognitive well-being, vulnerable groups, affordable public service facilities, economic agency, and environmental factors. Second, a combination of the CRITIC-TOPSIS method and k-means algorithm was used to grade and classify the inclusive development of the community. In this study, multisource data were used to measure the inclusiveness of communities in the core area of Wuhan’s inner city. The results show that the renewed communities are more inclusive than the unrenewed communities; however, even in the more inclusive and renewed communities, a lack of protection for vulnerable groups and a certain level of gentrification still exists.
TREML2 Gene Expression and Its Missense Variant rs3747742 Associate with White Matter Hyperintensity Volume and Alzheimer’s Disease-Related Brain Atrophy in the General Population
Authors: Kühn Annemarie Luise , Frenzel Stefan , Teumer Alexander , Wittfeld Katharina , Garvert Linda , Weihs Antoine , Homuth Georg , Prokisch Holger , Bülow Robin , Nauck Matthias , Völker Uwe , Völzke Henry , Grabe Hans Jörgen , Van der Auwera Sandra
Published: November 2022

Although the common pathology of Alzheimer’s disease (AD) and white matter hyperintensities (WMH) is disputed, the gene TREML2 has been implicated in both conditions: its whole-blood gene expression was associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E (APOE) ε4 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany). AD was assessed using a continuous pre-symptomatic MRI-based score evaluating a participant’s AD-related brain atrophy. In our study, increased whole-blood TREML2 gene expression was significantly associated with reduced WMH volume but not with the AD score. Conversely, rs3747742-C was significantly associated with a reduced AD score but not with WMH volume. The APOE status did not influence the associations. In sum, TREML2 robustly associated with WMH volume and AD-related brain atrophy on different molecular levels. Our results thus underpin TREML2’s role in neurodegeneration, might point to its involvement in AD and WMH via different biological mechanisms, and highlight TREML2 as a worthwhile target for disentangling the two pathologies.
Triplin: Functional Probing of Its Structure and the Dynamics of the Voltage-Gating Process
Authors: Colombini Marco , Barnes Kevin , Chang Kai-Ti , Younis Muhsin H. , Aguilella Vicente M.
Published: November 2022

Gram-negative bacteria have a large variety of channel-forming proteins in their outer membrane, generally referred to as porins. Some display weak voltage dependence. A similar trimeric channel former, named Triplin, displays very steep voltage dependence, rivaling that responsible for the electrical excitability of mammals, and high inter-subunit cooperativity. We report detailed insights into the molecular basis for these very unusual properties explored at the single-molecule level. By using chemical modification to reduce the charge on the voltage sensors, they were shown to be positively charged structures. Trypsin cleavage of the sensor eliminates voltage gating by cleaving the sensor. From asymmetrical addition of these reagents, the positively charged voltage sensors translocate across the membrane and are, thus, responsible energetically for the steep voltage dependence. A mechanism underlying the cooperativity was also identified. Theoretical calculations indicate that the charge on the voltage sensor can explain the rectification of the current flowing through the open pores if it is located near the pore mouth in the open state. All results support the hypothesis that one of the three subunits is oriented in a direction opposite to that of the other two. These properties make Triplin perhaps the most complex pore-forming molecular machine described to date.
Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver
Authors: Assalin Heloisa B. , De Almeida Kelly Cristiane Gabriel , Guadagnini Dioze , Santos Andrey , Teixeira Caio J. , Bordin Silvana , Rocha Guilherme Z. , Saad Mario J. A.
Published: November 2022

Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFβ downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.
Comparison of the Chemical Components, Efficacy and Mechanisms of Action of Chrysanthemum morifolium Flower and Its Wild Relative Chrysanthemum indicum Flower against Liver-Fire Hyperactivity Syndrome of Hypertension via Integrative Analyses
Authors: Wang Yue , Li Yangyu , Guo Wei , Yang Xiao , Qu Jiameng , Gao Mang , Chen Shuting , Dong Jiangru , Li Qing , Wang Tiejie
Published: November 2022

To clarify the differences in the clinical application scope of Chrysanthemum morifolium flower (CMF) and Chrysanthemum indicum flower (CIF), two herbs of similar origin, an integrated strategy of network pharmacology, molecular pharmacology, and metabolomics was employed, with a view to investigating the commonalities and dissimilarities in chemical components, efficacy and mechanisms of action. Initial HPLC-Q-TOF-MS analysis revealed that CMF and CIF had different flavonoid constituents. The biological processes underlying the therapeutic effects of CMF and CIF on liver-fire hyperactivity syndrome of hypertension (LFHSH) were predicted to be related to inflammatory response, fatty acid production, and other pathways based on network pharmacology analysis. ELISA, molecular docking, Western blot, and metabolomics techniques showed similar effects of CMF and CIF in lowering blood pressure, resistance to tissue, organ and functional damage, and dyslipidemia. However, distinct effects were found in the regulation of inflammatory response, PI3K-Akt and NF-κB signaling pathways, lipid anabolism, renin-angiotensin system, and metabolic abnormalities. The comparable efficacies of CMF and CIF, despite having distinct mechanisms of action, may be attributed to the integration and counteraction of their different regulating capabilities on the above anti-LFHSH mechanisms. This study offers a vital platform for assessment of differential and precise applications of herbs of close origin with similar but slightly different medicinal properties, and provides a research strategy for bridging Chinese medicine and modern precision medicine.
Constitutively Active Androgen Receptor in Hepatocellular Carcinoma
Authors: Montgomery Emma J. , Xing Enming , Campbell Moray J. , Li Pui-Kai , Blachly James S. , Tsung Allan , Coss Christopher C.
Published: November 2022

Hepatocellular carcinoma (HCC) is the predominant type of liver cancer and a leading cause of cancer-related death globally. It is also a sexually dimorphic disease with a male predominance both in HCC and in its precursors, non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The role of the androgen receptor (AR) in HCC has been well documented; however, AR-targeted therapies have failed to demonstrate efficacy in HCC. Building upon understandings of AR in prostate cancer (PCa), this review examines the role of AR in HCC, non-androgen-mediated mechanisms of induced AR expression, the existence of AR splice variants (AR-SV) in HCC and concludes by surveying current AR-targeted therapeutic approaches in PCa that show potential for efficacy in HCC in light of AR-SV expression.
Reproductive Outbreaks of Sogatella furcifera Mediated by Overexpression of the Nuclear Receptor USP under Pressure from Triflumezopyrim
Authors: Zhang Yuming , Ruan Yanwei , Gong Changwei , Zhang Shuirong , Zhang Jingyue , He Yunfeng , Wang Qiulin , Liu Dan , Pu Jian , Liu Xuemei , Jiang Chunxian , Wang Xuegui
Published: November 2022

Long-term pesticide-driven selection pressure is one of the main causes of insect outbreaks. In this study, we found that low doses of triflumezopyrim could increase the fecundity of white-backed planthoppers (Sogatella furcifera). By continuously screening 20 generations with a low dose of triflumezopyrim, a triflumezopyrim-resistant strain (Tri-strain, resistance ratio = 20.9-fold) was obtained. The average oviposition quantity and longevity of the Tri-strain (208.77 eggs and 21.31 days, respectively) were significantly higher than those of the susceptible strain (Sus-strain) (164.62 eggs and 17.85 days, respectively). To better understand the mechanism underlying the effects on reproduction, we detected the expression levels of several reproduction-related transcription factors in both the Tri- and Sus-strains. Ultraspiracle (USP) was significantly overexpressed in the Tri-strain. Knockdown of USP by RNAi severely inhibited the moulting process of S. furcifera and disrupted the development of female adult ovaries. Among the potential downstream target genes of USP, Kr-h1 (0.19-fold), Cht8 (0.56-fold) and GPCR A22 (0.31-fold) showed downregulated expression after USP-RNAi. In contrast, the expression of EcR (2.55-fold), which forms heterodimers with USP, was significantly upregulated. Furthermore, RNAi was performed on Kr-h1 in the Tri-strain, and the results show that larval moulting and the development of female adult ovaries were inhibited, consistent with the USP-RNAi results in S. furcifera. These results suggest that the transcription factors USP and Kr-h1 play important roles in the reproductive development of S. furcifera, and overexpression of USP and Kr-h1 in the Tri-resistant strain may result in reproductive outbreaks of pests.
Molecular Management of High-Grade Serous Ovarian Carcinoma
Authors: Punzón-Jiménez Paula , Lago Victor , Domingo Santiago , Simón Carlos , Mas Aymara
Published: November 2022

High-grade serous ovarian carcinoma (HGSOC) represents the most common form of epithelial ovarian carcinoma. The absence of specific symptoms leads to late-stage diagnosis, making HGSOC one of the gynecological cancers with the worst prognosis. The cellular origin of HGSOC and the role of reproductive hormones, genetic traits (such as alterations in P53 and DNA-repair mechanisms), chromosomal instability, or dysregulation of crucial signaling pathways have been considered when evaluating prognosis and response to therapy in HGSOC patients. However, the detection of HGSOC is still based on traditional methods such as carbohydrate antigen 125 (CA125) detection and ultrasound, and the combined use of these methods has yet to support significant reductions in overall mortality rates. The current paradigm for HGSOC management has moved towards early diagnosis via the non-invasive detection of molecular markers through liquid biopsies. This review presents an integrated view of the relevant cellular and molecular aspects involved in the etiopathogenesis of HGSOC and brings together studies that consider new horizons for the possible early detection of this gynecological cancer.
New Angucycline Glycosides from a Marine-Derived Bacterium Streptomyces ardesiacus
Authors: Anh Cao Van , Kwon Joo-Hee , Kang Jong Soon , Lee Hwa-Sun , Heo Chang-Su , Shin Hee Jae
Published: November 2022

Chemical investigation of the ethyl acetate extract from the culture broth of the marine-derived actinobacterium Streptomyces ardesiacus 156VN-095 led to the isolation of three hitherto undescribed angucycline glycosides, including urdamycins W and X (1 and 2) and grincamycin U (9), as well as their seven known congeners. The structures of the new compounds were elucidated by means of spectroscopic methods (HRESIMS, 1D and 2 D NMR) and comparison of their experimental data with literature values. Compounds 1–3 and 9 were evaluated for their anti-Gram-positive bacterial effect and cytotoxicity against six cancer cell lines. Compound 1 displayed significant cytotoxicity against all the tested cell lines with GI50 values of 0.019–0.104 µM. Collectively, these findings highlight the potential of angucycline glycosides as leading structures for the development of new anti-cancer drugs.
Molecular Mechanism and Application of Somatic Cell Cloning in Mammals—Past, Present and Future
Authors: Samiec Marcin
Published: November 2022

Thus far, nearly 25 mammalian species have been cloned by intra- or interspecies somatic cell nuclear transfer (SCNT) [...]
Microbiota-Derived Extracellular Vesicles Detected in Human Blood from Healthy Donors
Authors: Schaack Béatrice , Hindré Thomas , Quansah Nyamekye , Hannani Dalil , Mercier Corinne , Laurin David
Published: November 2022

The microbiota constitutes an important part of the holobiont in which extracellular vesicles (EVs) are key players in health, especially regarding inter- and intra-kingdom communications. Analysis of EVs from the red blood cell concentrates of healthy donors revealed variable amounts of OmpA and LPS in 12 of the 14 analyzed samples, providing indirect experimental evidence of the presence of microbiota EVs in human circulating blood in the absence of barrier disruption. To investigate the role of these microbiota EVs, we tracked the fusion of fluorescent Escherichia coli EVs with blood mononuclear cells and showed that, in the circulating blood, these EVs interacted almost exclusively with monocytes. This study demonstrates that bacterial EVs constitute critical elements of the host–microbiota cellular communication. The analysis of bacterial EVs should thus be systematically included in any characterization of human EVs.
Two Subgroups within the GH43_36 α-l-Arabinofuranosidase Subfamily Hydrolyze Arabinosyl from Either Mono-or Disubstituted Xylosyl Units in Wheat Arabinoxylan
Authors: Leschonski Kai P. , Kaasgaard Svend G. , Spodsberg Nikolaj , Krogh Kristian B. R. M. , Kabel Mirjam A.
Published: November 2022

Fungal arabinofuranosidases (ABFs) catalyze the hydrolysis of arabinosyl substituents (Ara) and are key in the interplay with other glycosyl hydrolases to saccharify arabinoxylans (AXs). Most characterized ABFs belong to GH51 and GH62 and are known to hydrolyze the linkage of α-(1→2)-Ara and α-(1→3)-Ara in monosubstituted xylosyl residues (Xyl) (ABF-m2,3). Nevertheless, in AX a substantial number of Xyls have two Aras (i.e., disubstituted), which are unaffected by ABFs from GH51 and GH62. To date, only two fungal enzymes have been identified (in GH43_36) that specifically release the α-(1→3)-Ara from disubstituted Xyls (ABF-d3). In our research, phylogenetic analysis of available GH43_36 sequences revealed two major clades (GH43_36a and GH43_36b) with an expected substrate specificity difference. The characterized fungal ABF-d3 enzymes aligned with GH43_36a, including the GH43_36 from Humicola insolens (HiABF43_36a). Hereto, the first fungal GH43_36b (from Talaromyces pinophilus) was cloned, purified, and characterized (TpABF43_36b). Surprisingly, TpABF43_36b was found to be active as ABF-m2,3, albeit with a relatively low rate compared to other ABFs tested, and showed minor xylanase activity. Novel specificities were also discovered for the HiABF43_36a, as it also released α-(1→2)-Ara from a disubstitution on the non-reducing end of an arabinoxylooligosaccharide (AXOS), and it was active to a lesser extent as an ABF-m2,3 towards AXOS when the Ara was on the second xylosyl from the non-reducing end. In essence, this work adds new insights into the biorefinery of agricultural residues.
Alternate-Day Fasting Ameliorates Newly Established Sjögren’s Syndrome-like Sialadenitis in Non-Obese Diabetic Mice
Authors: Li Dongfang , Onodera Shoko , Deng Shu , Alnujaydi Bashaer , Yu Qing , Zhou Jing
Published: November 2022

Intermittent fasting confers protections to various diseases including autoimmune disorders, but the specific effects of intermittent fasting on Sjögren’s syndrome (SS) remains inconclusive. The present study was undertaken to determine the specific impact of alternate-day fasting (ADF) on newly established SS-like sialadenitis using non-obese diabetic (NOD) mice. Female NOD mice were deprived of food every other day from 10 to 13 weeks of age, the early stage of established SS, and then analyzed for the disease characteristics. Mice in the ADF group had higher salivary flow rate and attenuated submandibular gland (SMG) inflammation, compared to the control mice fed with standard chow ad libitum. The improvements were accompanied with a decrease in the total leukocytes, T and B lymphocytes and activated CD4 and CD8 T cells, and a down-regulation of pro-inflammatory cytokines IFN-γ and IL-17, chemokine receptor CXCR3 and its ligands CXCL9 and CXCL11 in the SMGs. ADF also led to elevated mRNA levels of water channel protein aquaporin 5 and tight junction protein claudin-1, two factors crucial for normal salivary secretion in the SMGs. In addition, ADF reduced the proportion of IFN-γ- and IL-17- expressing CD4 T cells and diminished mRNA levels of IFN-γ, TNF-α, and IL-17 in the total submandibular draining lymph node cells. Taken together, ADF is effective in ameliorating newly established SS-associated salivary gland exocrinopathy in NOD mice.
Targeting Inflammation and Regeneration: Scaffolds, Extracellular Vesicles, and Nanotechnologies as Cell-Free Dual-Target Therapeutic Strategies
Authors: Peshkova Maria , Kosheleva Nastasia , Shpichka Anastasia , Radenska-Lopovok Stefka , Telyshev Dmitry , Lychagin Alexey , Li Fangzhou , Timashev Peter , Liang Xing-Jie
Published: November 2022

Osteoarthritis (OA) affects over 250 million people worldwide and despite various existing treatment strategies still has no cure. It is a multifactorial disease characterized by cartilage loss and low-grade synovial inflammation. Focusing on these two targets together could be the key to developing currently missing disease-modifying OA drugs (DMOADs). This review aims to discuss the latest cell-free techniques applied in cartilage tissue regeneration, since they can provide a more controllable approach to inflammation management than the cell-based ones. Scaffolds, extracellular vesicles, and nanocarriers can be used to suppress inflammation, but they can also act as immunomodulatory agents. This is consistent with the latest tissue engineering paradigm, postulating a moderate, controllable inflammatory reaction to be beneficial for tissue remodeling and successful regeneration.
PAC1, VPAC1, and VPAC2 Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
Authors: Tasma Zoe , Siow Andrew , Harris Paul W. R. , Brimble Margaret A. , O’Carroll Simon J. , Hay Debbie L. , Walker Christopher S.
Published: November 2022

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide expressed in the trigeminal ganglia (TG). The TG conducts nociceptive signals in the head and may play roles in migraine. PACAP infusion provokes headaches in healthy individuals and migraine-like attacks in patients; however, it is not clear whether targeting this system could be therapeutically efficacious. To effectively target the PACAP system, an understanding of PACAP receptor distribution is required. Therefore, this study aimed to characterize commercially available antibodies and use these to detect PACAP-responsive receptors in the TG. Antibodies were initially validated in receptor transfected cell models and then used to explore receptor expression in rat and human TG. Antibodies were identified that could detect PACAP-responsive receptors, including the first antibody to differentiate between the PAC1n and PAC1s receptor splice variants. PAC1, VPAC1, and VPAC2 receptor-like immunoreactivity were observed in subpopulations of both neuronal and glial-like cells in the TG. In this study, PAC1, VPAC1, and VPAC2 receptors were detected in the TG, suggesting they are all potential targets to treat migraine. These antibodies may be useful tools to help elucidate PACAP-responsive receptor expression in tissues. However, most antibodies exhibited limitations, requiring the use of multiple methodologies and the careful inclusion of controls.
Effect of Goreisan, a Japanese Traditional Medicine, on Cortical Spreading Depolarization in Mice
Authors: Iba Chisato , Unekawa Miyuki , Izawa Yoshikane , Nakahara Jin , Takizawa Tsubasa
Published: November 2022

Goreisan, a traditional Japanese Kampo medicine, is often used to treat headaches, including migraines; however, the underlying mechanisms remain unknown. Therefore, we investigated whether chronic treatment with Goreisan affects cortical spreading depolarization (CSD) in migraines. CSD susceptibility was assessed in male and female C57BL/6 mice by comparing CSD threshold, propagation velocity, and CSD frequency between animals treated with Goreisan for approximately 3 weeks and the corresponding controls with a potassium-induced CSD model. No significant differences were observed in CSD susceptibility between mice that were chronically treated with Goreisan and the control mice. Additionally, no significant differences were observed in other physiological parameters, including body weight, blood gases, and blood pressure. CSD susceptibility was not affected by chronic treatment with Goreisan, which suggests that the drug treats headaches via mechanisms that do not involve CSD modulation.
Terconazole, an Azole Antifungal Drug, Increases Cytotoxicity in Antimitotic Drug-Treated Resistant Cancer Cells with Substrate-Specific P-gp Inhibitory Activity
Authors: Lee Ji Sun , Oh Yunmoon , Park Jae Hyeon , Kyung So Young , Kim Hyung Sik , Yoon Sungpil
Published: November 2022

Azole antifungal drugs have been shown to enhance the cytotoxicity of antimitotic drugs in P-glycoprotein (P-gp)-overexpressing-resistant cancer cells. Herein, we examined two azole antifungal drugs, terconazole (TCZ) and butoconazole (BTZ), previously unexplored in resistant cancers. We found that both TCZ and BTZ increased cytotoxicity in vincristine (VIC)-treated P-gp-overexpressing drug-resistant KBV20C cancer cells. Following detailed analysis, low-dose VIC + TCZ exerted higher cytotoxicity than co-treatment with VIC + BTZ. Furthermore, we found that VIC + TCZ could increase apoptosis and induce G2 arrest. Additionally, low-dose TCZ could be combined with various antimitotic drugs to increase their cytotoxicity in P-gp-overexpressing antimitotic drug-resistant cancer cells. Moreover, TCZ exhibited P-gp inhibitory activity, suggesting that the inhibitory activity of P-gp plays a role in sensitization afforded by VIC + TCZ co-treatment. We also evaluated the cytotoxicity of 12 azole antifungal drugs at low doses in drug-resistant cancer cells. VIC + TCZ, VIC + itraconazole, and VIC + posaconazole exhibited the strongest cytotoxicity in P-gp-overexpressing KBV20C and MCF-7/ADR-resistant cancer cells. These drugs exerted robust P-gp inhibitory activity, accompanied by calcein-AM substrate efflux. Given that azole antifungal drugs have long been used in clinics, our results, which reposition azole antifungal drugs for treating P-gp-overexpressing-resistant cancer, could be employed to treat patients with drug-resistant cancer rapidly.
Fabrication of Multilayered Biofunctional Material with an Enamel-like Structure
Authors: Zhang Yu Yuan , Li Quan Li , Wong Hai Ming
Published: November 2022

The oral cavity is an environment with diverse bacteria; thus, antibacterial materials are crucial for treating and preventing dental diseases. There is a high demand for materials with an enamel-like architecture because of the high failure rate of dental restorations, due to the physical differences between dental materials and enamel. However, recreating the distinctive apatite composition and hierarchical architecture of enamel is challenging. The aim of this study was to synthesize a novel material with an enamel-like structure and antibacterial ability. We established a non-cell biomimetic method of evaporation-based bottom-up self-assembly combined with a layer-by-layer technique and introduced an antibacterial agent (graphene oxide) to fabricate a biofunctional material with an enamel-like architecture and antibacterial ability. Specifically, enamel-like graphene oxide-hydroxyapatite crystals, formed on a customized mineralization template, were assembled into an enamel-like prismatic structure with a highly organized orientation preferentially along the c-axis through evaporation-based bottom-up self-assembly. With the aid of layer-by-layer absorption, we then fabricated a bulk macroscopic multilayered biofunctional material with a hierarchical enamel-like architecture. This enamel-inspired biomaterial could effectively resolve the problem in dental restoration and brings new prospects for the synthesis of other enamel-inspired biomaterials.