bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Study on the Shear Behavior of Reinforced Highly Ductile Fiber-Reinforced Concrete Beams with Stirrups
Authors: Zhang Min , Deng Mingke , Yang Jiasheng , Zhang Yangxi
Published: August 2022

The aim of this study is to improve the shear behavior of reinforced concrete (RC) beams with stirrups by using highly ductile fiber-reinforced concrete (HDC), which is a fiber-reinforced cement-based composite material with tensile-strain-hardening properties. Twelve reinforced HDC (RHDC) beams and three RC beams with stirrups were tested under a concentrated load. The experimental parameters involved the shear span to effective depth ratio, stirrup ratio, and longitudinal reinforcement ratio. The results revealed that the mode of failure of RHDC beams, which exhibited better ductility than RC beams, included diagonal compression, shear compression, diagonal tension, and flexural shear failure. RHDC beams exhibited stable multiple crack propagation behavior and satisfactory integrity, thus showing that HDC effectively restricted the development of shear cracks and improved the damage resistance of beams. Compared with RC beams, the shear strength, displacement ductility factor, and deflection-clear span ratios corresponding to the peak load and ultimate deflection increased by up to 30.5%, 44.9%, 150.0%, and 148.0%, respectively. RHDC beams exhibited higher residual strength and deformation capacity than RC beams, thus indicating that HDC significantly improved the brittle shear failure mode. Specimens H-1 and H-2 exhibited the largest improvement in shear strength and displacement ductility factor, respectively, compared with RC beams. The shear strength of RHDC beams increased as the shear span to effective depth ratio decreased. For RHDC beams with the same shear span to effective depth ratio, the shear strength increased with the increase in the longitudinal reinforcement ratio and stirrup ratio under shear compression failure.
Factors That Influence the Quantification of the Embodied Carbon Emission of Prefabricated Buildings: A Systematic Review, Meta-Analysis and the Way Forward
Authors: Chen Yuan , Zhou Yuwei , Feng Weimin , Fang Yuan , Feng Anqi
Published: August 2022

Prefabricated buildings and off-site construction are increasingly adopted in modern construction. As one of the most concerning environmental impacts, the embodied carbon emission of prefabricated buildings has been extensively investigated in recent years. Due to the various influencing factors of carbon quantification, such as building characteristics, quantification boundary, emission sources, and quantification methods, no consensus has been reached so far. The impacts of the influencing factors on carbon quantification remain unclear. To fill this gap, this paper provides a systematic review and meta-analysis to comprehensively evaluate the recent research concerning the quantification of the embodied carbon emission of prefabricated buildings. In total, 43 peer-reviewed articles (96 building cases) were screened and analyzed. Twelve influencing factors of embodied carbon quantification have been identified and analyzed to give rise to a synthesized conclusion. The results of the meta-analysis indicated that the embodied carbon emission of prefabricated buildings varied significantly from 26.6 to 1644.4 kgCO2e/m2 in the reviewed literature. The results showed that some of the quantification factors could significantly influence the quantification results, such as the building structure forms, level of prefabrication, type of greenhouse gas considered, and data sources, while some factors have a lesser impact on carbon quantification results, such as the function of the building, quantification methods adopted, quantification tools/software used, and carbon inventory databases applied. The findings of this research provide readers with an in-depth and critical understanding of the quantification of the embodied carbon emission of prefabricated buildings. Research gaps and suggestions for future research are also provided based on the results of this work.
Study on the Relationship between Restoration Benefit and Visual Satisfaction of LONG-PLAN’s Indoor Vertical Greenery
Authors: Xiao Lei , Wu Ruoyu , Huang Juqing , Yang Xing , Xu Anjiang
Published: August 2022

This study investigates the psychological restorative benefits of indoor vertical greenery and its relationship with visual satisfaction. Taking the Solar Decathlon China 2018 champion project “LONG-PLAN” as the experimental field, we conducted a questionnaire survey to evaluate the effect of indoor vertical greenery on creating a restorative environment. Then we further studied the relationship between the restorative environmental factors and visual satisfaction of indoor vertical greenery. The results show that: (1) Indoor vertical greenery has a positive impact on the subjective restoration of respondents (the average value of PRS = 4.150). (2) The three factors of “being away,” “fascination and compatibility,” and the “extent” of environmental restoration have a significant positive correlation with the visual satisfaction of indoor vertical greenery (the correlation coefficient values are 0.403, 0.627, and 0.425, respectively, p < 0.01). (3) In the stepwise regression analysis of the three factors and the visual satisfaction of indoor vertical greenery, only “fascination and compatibility” show a significant positive correlation (the regression coefficient = 0.753, p < 0.01). (4) The visual satisfaction of indoor vertical greenery has a significantly positive impact on environmental recovery (the regression coefficient = 0.459, p < 0.01). The study shows that indoor vertical greenery improves visual satisfaction and contributes to a restorative environment. In addition, the study provides further evidence of the mutual facilitation between restorative benefits and visual satisfaction.
Ablative Radiotherapy as a Strategy to Overcome TKI Resistance in EGFR-Mutated NSCLC
Authors: Novak Jennifer , Salgia Ravi , West Howard , Villalona-Calero Miguel A , Sampath Sagus , Williams Terence , Villaflor Victoria , Massarelli Erminia , Pathak Ranjan , Koczywas Marianna , Chau Brittney , Amini Arya
Published: August 2022

Tyrosine kinase inhibitor (TKI) therapy is the recommended first-line treatment for metastatic non-small-cell lung cancer (NSCLC) positive for epidermal growth factor receptor (EGFR) gene mutation. However, most individuals treated with TKI therapy for EGFR-mutant NSCLC will develop tumor resistance to TKI therapy. Therapeutic strategies to overcome TKI resistance are the topic of several ongoing clinical trials. One potential strategy, which has been explored in numerous trials, is the treatment of progressive sites of disease with stereotactic body radiation treatment (SBRT) or stereotactic radiosurgery (SRS). We sought to review the literature pertaining to the use of local ablative radiation therapy in the setting of acquired resistance to TKI therapy and to discuss stereotactic radiation therapy as a strategy to overcome TKI resistance.
Work Placement and Job Satisfaction in Long-Term Childhood Cancer Survivors: The Impact of Late Effects
Authors: Dionisi-Vici Margherita , Godono Alessandro , Castiglione Anna , Gatti Filippo , Fortunati Nicoletta , Clari Marco , Conti Alessio , Zucchetti Giulia , Biasin Eleonora , Varetto Antonella , Pira Enrico , Fagioli Franca , Brignardello Enrico , Felicetti Francesco
Published: August 2022

Late effects of cancer and its treatments during childhood or adolescence can impact work placement and increase the risk of unemployment. The aim of this study is to describe the work placement and the perceived job and economic satisfaction of long-term childhood cancer survivors (CCS). Jobs have been categorized according to the International Standard Classification of Occupations version 08 (ISCO-08), and satisfaction has been evaluated through the Satisfaction Profile (SAT-P). Out of 240 CCS (female = 98) included: 53 were students, 46 were unemployed and 141 were employed. Within unemployed survivors, 89.13% were affected by late effects (n = 41). The presence of at least one severe late effect was significantly associated with the probability of unemployment (OR 3.21; 95% CI 1.13–9.12, p < 0.050), and having any late effect was inversely related to the level of satisfaction of the financial situation of unemployed CCS (b −35.47; 95% CI −59.19, −11.74, p = 0.004). Our results showed that being a survivor with severe comorbidities has a significantly negative impact on occupation and worsens the perception of satisfaction of economic situations. Routinary follow-up care of CCS should include the surveillance of socioeconomic development and provide interventions, helping them to reach jobs suitable for their health.
Simplified Selection Criteria for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer
Authors: Son Joo-Hyuk , Lee Jimin , Yum Sun-Hyung , Kim Jeeyeon , Kong Tae-Wook , Chang Suk-Joon , Ryu Hee-Sug
Published: August 2022

(1) Background: Multiple confounding factors influence the indications for secondary cytoreductive surgery (SCS) in patients with ovarian cancer (OC). We aimed to identify the factors associated with patients most likely to benefit from SCS. (2) Methods: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer from 2003 to 2021. The potential factors influencing treatment outcomes and survival between patients who received chemotherapy alone and those who received SCS after recurrence were evaluated. (3) Results: Recurrent OC was identified in 262 patients, with a median age of 53 (20–80) years. Of these patients, 87.4% had an initial stage III/IV disease. Eighty-nine (34%) patients received SCS. The median survival was 41.0 (95% confidence interval [CI], 37.4–44.5) months and 88.0 (95% CI, 64.2–111.7) months in the chemotherapy and surgery groups, respectively. A multivariate analysis showed limited regional carcinomatosis (single region or up to three regions with limited carcinomatosis) (p = 0.045) as the only significant factor for predicting no residual disease after SCS. In platinum-sensitive recurrent patients with limited regional recurrence, the complete resection rate was 87.6%. (4) Conclusions: SCS had a significant impact on survival in the selected patient population. Limited regional recurrence (single region or up to three regions with limited carcinomatosis) may be a simple criterion for SCS in platinum-sensitive recurrent OC patients.
Effects of Green Tea Catechins on Prostate Cancer Chemoprevention: The Role of the Gut Microbiome
Authors: Kumar Nagi B. , Hogue Stephanie , Pow-Sang Julio , Poch Michael , Manley Brandon J. , Li Roger , Dhillon Jasreman , Yu Alice , Byrd Doratha A.
Published: August 2022

Accumulating evidence supports green tea catechins (GTCs) in chemoprevention for prostate cancer (PCa), a leading cause of cancer morbidity and mortality among men. GTCs include (−)-epigallocatechin-3-gallate, which may modulate the molecular pathways implicated in prostate carcinogenesis. Prior studies of GTCs suggested that they are bioavailable, safe, and effective for modulating clinical and biological markers implicated in prostate carcinogenesis. GTCs may be of particular benefit to those with low-grade PCas typically managed with careful monitoring via active surveillance (AS). Though AS is recommended, it has limitations including potential under-grading, variations in eligibility, and anxiety reported by men while on AS. Secondary chemoprevention of low-grade PCas using GTCs may help address these limitations. When administrated orally, the gut microbiome enzymatically transforms GTC structure, altering its bioavailability, bioactivity, and toxicity. In addition to xenobiotic metabolism, the gut microbiome has multiple other physiological effects potentially involved in PCa progression, including regulating inflammation, hormones, and other known/unknown pathways. Therefore, it is important to consider not only the independent roles of GTCs and the gut microbiome in the context of PCa chemoprevention, but how gut microbes may relate to individual responses to GTCs, which, in turn, can enhance clinical decision-making.
Stereotactic Radiosurgery for Lung Cancer with a Risk-Adapted Strategy Using the Volumetric Modulated Arc Therapy Technique: A Single Arm Phase II Study
Authors: Yamamoto Takaya , Katagiri Yu , Tsukita Yoko , Matsushita Haruo , Umezawa Rei , Katsuta Yoshiyuki , Kadoya Noriyuki , Takahashi Noriyoshi , Suzuki Yu , Takeda Kazuya , Kishida Keita , Omata So , Miyauchi Eisaku , Saito Ryota , Jingu Keiichi
Published: August 2022

Purpose: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. Materials and Methods: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1–5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. Results: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3–22.2%), 20.1% (95% CI: 6.0–40.2%), 59.2% (95% CI: 34.4–77.3%), and 78.2% (95% CI: 51.4–91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. Conclusions: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity.
Current Imaging Diagnosis of Hepatocellular Carcinoma
Authors: Chartampilas Evangelos , Rafailidis Vasileios , Georgopoulou Vivian , Kalarakis Georgios , Hatzidakis Adam , Prassopoulos Panos
Published: August 2022

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer related death worldwide. Radiology has traditionally played a central role in HCC management, ranging from screening of high-risk patients to non-invasive diagnosis, as well as the evaluation of treatment response and post-treatment follow-up. From liver ultrasonography with or without contrast to dynamic multiple phased CT and dynamic MRI with diffusion protocols, great progress has been achieved in the last decade. Throughout the last few years, pathological, biological, genetic, and immune-chemical analyses have revealed several tumoral subtypes with diverse biological behavior, highlighting the need for the re-evaluation of established radiological methods. Considering these changes, novel methods that provide functional and quantitative parameters in addition to morphological information are increasingly incorporated into modern diagnostic protocols for HCC. In this way, differential diagnosis became even more challenging throughout the last few years. Use of liver specific contrast agents, as well as CT/MRI perfusion techniques, seem to not only allow earlier detection and more accurate characterization of HCC lesions, but also make it possible to predict response to treatment and survival. Nevertheless, several limitations and technical considerations still exist. This review will describe and discuss all these imaging modalities and their advances in the imaging of HCC lesions in cirrhotic and non-cirrhotic livers. Sensitivity and specificity rates, method limitations, and technical considerations will be discussed.
How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needle Biopsy? A Study of Paired Core-Needle Biopsies and Surgical Specimens in Early Breast Cancer
Authors: Saghir Hani , Veerla Srinivas , Malmberg Martin , Rydén Lisa , Ehinger Anna , Saal Lao H. , Vallon-Christersson Johan , Borg Åke , Hegardt Cecilia , Larsson Christer , Haidar Alaa , Hedenfalk Ingrid , Loman Niklas , Kimbung Siker
Published: August 2022

In early breast cancer, a preoperative core-needle biopsy (CNB) is vital to confirm the malignancy of suspected lesions and for assessing the expression of treatment predictive and prognostic biomarkers in the tumor to choose the optimal treatments, emphasizing the importance of obtaining reliable results when biomarker status is assessed on a CNB specimen. This study aims to determine the concordance between biomarker status assessed as part of clinical workup on a CNB compared to a medically untreated surgical specimen. Paired CNB and surgical specimens from 259 patients that were part of the SCAN-B cohort were studied. The concordance between immunohistochemical (IHC) and gene expression (GEX) based biomarker status was investigated. Biomarkers of interest included estrogen receptor (ER; specifically, the alpha variant), progesterone receptor (PgR), Ki67, HER2, and tumor molecular subtype. In general, moderate to very good correlation in biomarker status between the paired CNB and surgical specimens was observed for both IHC assessment (83–99% agreement, kappa range 0.474–0.917) and GEX assessment (70–97% agreement, kappa range 0.552–0.800), respectively. However, using IHC, 52% of cases with low Ki67 status in the CNB shifted to high Ki67 status in the surgical specimen (McNemar’s p = 0.011). Similarly, when using GEX, a significant shift from negative to positive ER (47%) and from low to high Ki67 (16%) was observed between the CNB and surgical specimen (McNemar’s p = 0.027 and p = 0.002 respectively). When comparing biomarker status between different techniques (IHC vs. GEX) performed on either CNBs or surgical specimens, the agreement in ER, PgR, and HER2 status was generally over 80% in both CNBs and surgical specimens (kappa range 0.395–0.708), but Ki67 and tumor molecular subtype showed lower concordance levels between IHC and GEX (48–62% agreement, kappa range 0.152–0.398). These results suggest that both the techniques used for collecting tissue samples and analyzing biomarker status have the potential to affect the results of biomarker assessment, potentially also impacting treatment decisions and patient survival outcomes.
Levulinic Acid Is a Key Strategic Chemical from Biomass
Authors: Victor Amudhavalli , Sharma Pankaj , Pulidindi Indra Neel , Gedanken Aharon
Published: August 2022

Levulinic acid (LA) is one of the top twelve chemicals listed by the US Department of Energy that can be derived from biomass. It serves as a building block and platform chemical for producing a variety of chemicals, fuels and materials which are currently produced in fossil based refineries. LA is a key strategic chemical, as fuel grade chemicals and plastic substitutes can be produced by its catalytic conversion. LA derivatisation to various product streams, such as alkyl levulinates via esterification, γ-valerolactone via hydrogenation and N-substituted pyrrolidones via reductive amination and many other transformations of commercial utility are possible owing to the two oxygen functionalities, namely, carbonyl and carboxyl groups, present within the same substrate. Various biomass feedstock, such as agricultural wastes, marine macroalgae, and fresh water microalgae were successfully converted to LA in high yields. Finding a substitute to mineral acid catalysts for the conversion of biomass to LA is a challenge. The use of an ultrasound technique facilitated the production of promising nano-solid acid catalysts including Ga salt of molybophosphoric acid and Ga deposited mordenite zeolite, with optimum amounts of Lewis and Bronsted acidities needed for the conversion of glucose to LA in high yields, being 56 and 59.9 wt.% respectively. Microwave irradiation technology was successfully utilized for the accelerated production of LA (53 wt.%) from glucose in a short duration of 6 min, making use of the unique synergistic catalytic activity of ZnBr2 and HCl.
Hollow CuFe2O4/MgFe2O4 Heterojunction Boost Photocatalytic Oxidation Activity for Organic Pollutants
Authors: Zhang Zhicheng , Cai Wei , Rong Shaopeng , Qu Hongxia , Xie Huifang
Published: August 2022

P-n heterojunction-structured CuFe2O4/MgFe2O4 hollow spheres with a diameter of 250 nm were synthesized using a template-free solvothermal method, and time-dependent morphological studies were carried out to investigate the hollow formation mechanism. The CuFe2O4/MgFe2O4 with a molar ratio of 1:2 (Cu:Mg) had the highest degradation efficiency with the model organic dye Acid Orange 7, with a degradation rate of 91.96% over 60 min. The synthesized CuFe2O4/MgFe2O4 nanocomposites were characterized by XRD, TEM, HRTEM, UV-vis spectroscopy, Mott–Schottky, and EIS. Due to the synthesis of the p-n heterojunction, CuFe2O4/MgFe2O4 has efficient photogenerated carriers, and the hollow structure has a higher specific surface area and stronger adsorption capacity, which is significantly better than that of CuFe2O4 and MgFe2O4 in terms of photocatalytic performance. The outstanding performance shows that the p-n heterostructure of CuFe2O4/MgFe2O4 has potential for application in wastewater degradation.
The Water Transport System in Astrocytes–Aquaporins
Authors: Zhou Zuoyi , Zhan Jiangshan , Cai Qingyun , Xu Fanqing , Chai Ruichao , Lam Kalista , Luan Zuo , Zhou Guoying , Tsang Sue , Kipp Markus , Han Wenling , Zhang Rong , Yu Albert Cheung Hoi
Published: August 2022

Astrocytes have distinctive morphological and functional characteristics, and are found throughout the central nervous system. Astrocytes are now known to be far more than just housekeeping cells in the brain. Their functions include contributing to the formation of the blood–brain barrier, physically and metabolically supporting and communicating with neurons, regulating the formation and functions of synapses, and maintaining water homeostasis and the microenvironment in the brain. Aquaporins (AQPs) are transmembrane proteins responsible for fast water movement across cell membranes. Various subtypes of AQPs (AQP1, AQP3, AQP4, AQP5, AQP8 and AQP9) have been reported to be expressed in astrocytes, and the expressions and subcellular localizations of AQPs in astrocytes are highly correlated with both their physiological and pathophysiological functions. This review describes and summarizes the recent advances in our understanding of astrocytes and AQPs in regard to controlling water homeostasis in the brain. Findings regarding the features of different AQP subtypes, such as their expression, subcellular localization, physiological functions, and the pathophysiological roles of astrocytes are presented, with brain edema and glioma serving as two representative AQP-associated pathological conditions. The aim is to provide a better insight into the elaborate “water distribution” system in cells, exemplified by astrocytes, under normal and pathological conditions.
Expression of IL-37 Induces a Regulatory T-Cell-like Phenotype and Function in Jurkat Cells
Authors: Osborne Douglas Grant , Domenico Joanne , Fujita Mayumi
Published: August 2022

The anti-inflammatory cytokine interleukin-37 (IL-37) plays a key role in inhibiting innate and adaptive immunity. Past results have shown that IL-37 is elevated in human Treg cells compared to other T cell subsets and contributes to enhancing the Treg transcription factor, forkhead box protein P3 (FOXP3). However, it is unknown if ectopic expression of IL-37 in non-Treg CD4+ T cells can lead to the development of Treg phenotype and function. In the present study, we used a PrimeFlow® RNA assay and confirmed elevated IL37 expression in human Treg cells. We then stably transfected the non-Treg CD4+ T cell leukemia cell line, E6 Jurkat cells, with IL37 and found significant induction of the Treg phenotype. These IL-37-expressing Jurkat cells had elevated CTLA-4 and FOXP3 and produced IL-10. In conjunction with the Treg phenotype, IL-37-expressing Jurkat cells suppressed T cell activation/proliferation, comparable to human primary Treg cells. The creation of this stable human Treg-like cell line has the potential to provide further assistance for in vitro studies of human Treg cells, as it is more convenient than the use of primary human Treg cells. Furthermore, it provides insights into Treg cell biology and function.
Chronic Hyperglycemia Compromises Mitochondrial Function in Corneal Epithelial Cells: Implications for the Diabetic Cornea
Authors: Mussi Natalia , Stuard Whitney L. , Sanches Jose Marcos , Robertson Danielle M.
Published: August 2022

Mitochondrial dysfunction is a major pathophysiological event leading to the onset of diabetic complications. This study investigated the temporal effects of hyperglycemia on mitochondrial metabolism in corneal epithelial cells. To accomplish this, human telomerase-immortalized corneal epithelial cells were cultured in a defined growth medium containing 6 mM glucose. To simulate hyperglycemia, cells were cultured in a medium containing 25 mM D-glucose, and control cells were cultured in mannitol. Using metabolic flux analysis, there was a hyperosmolar-mediated increase in mitochondrial respiration after 24 h. By day 5, there was a decrease in spare respiratory capacity in cells subject to high glucose that remained suppressed throughout the 14-day period. Although respiration remained high through day 9, glycolysis was decreased. Mitochondrial respiration was decreased by day 14. This was accompanied by the restoration of glycolysis to normoglycemic levels. These changes paralleled a decrease in mitochondrial polarization and cell cycle arrest. Together, these data show that chronic but not acute hyperglycemic stress leads to mitochondrial dysfunction. Moreover, the hyperglycemia-induced loss of spare respiratory capacity reduces the ability of corneal epithelial cells to respond to subsequent stress. Compromised mitochondrial function represents a previously unexplored mechanism that likely contributes to corneal complications in diabetes.
Cannabinoids and PPAR Ligands: The Future in Treatment of Polycystic Ovary Syndrome Women with Obesity and Reduced Fertility
Authors: Przybycień Piotr , Gąsior-Perczak Danuta , Placha Wojciech
Published: August 2022

Cannabinoids (CBs) are used to treat chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis spasticity. Recently, the medicinal use of CBs has attracted increasing interest as a new therapeutic in many diseases. Data indicate a correlation between CBs and PPARs via diverse mechanisms. Both the endocannabinoid system (ECS) and peroxisome proliferator-activated receptors (PPARs) may play a significant role in PCOS and PCOS related disorders, especially in disturbances of glucose-lipid metabolism as well as in obesity and fertility. Taking into consideration the ubiquity of PCOS in the human population, it seems indispensable to search for new potential therapeutic targets for this condition. The aim of this review is to examine the relationship between metabolic disturbances and obesity in PCOS pathology. We discuss current and future therapeutic interventions for PCOS and related disorders, with emphasis on the metabolic pathways related to PCOS pathophysiology. The link between the ECS and PPARs is a promising new target for PCOS, and we examine this relationship in depth.
Rare Inherited Cholestatic Disorders and Molecular Links to Hepatocarcinogenesis
Authors: Jeyaraj Rebecca , Kelly Deirdre
Published: August 2022

Hepatocellular carcinoma (HCC) is the most common primary liver cancer affecting adults and the second most common primary liver cancer affecting children. Recent years have seen a significant increase in our understanding of the molecular changes associated with HCC. However, HCC is a complex disease, and its molecular pathogenesis, which likely varies by aetiology, remains to be fully elucidated. Interestingly, some inherited cholestatic disorders that manifest in childhood are associated with early HCC development. This review will thus explore how three genes that are associated with liver disease in childhood (ABCB11, TJP2 and VPS33B) might play a role in the initiation and progression of HCC. Specifically, chronic bile-induced damage (caused by ABCB11 changes), disruption of intercellular junction formation (caused by TJP2 changes) and loss of normal apical–basal cell polarity (caused by VPS33B changes) will be discussed as possible mechanisms for HCC development.
Quantitative and Qualitative Changes in the Genetic Diversity of Bacterial Communities in Anaerobic Bioreactors with the Diatomaceous Earth/Peat Cell Carrier
Authors: Pilarska Agnieszka A. , Wolna-Maruwka Agnieszka , Niewiadomska Alicja , Grządziel Jarosław , Gałązka Anna , Paluch Emil , Borowiak Klaudia , Pilarski Krzysztof
Published: August 2022

This paper analyses the impact of the diatomaceous earth/peat (DEP; 3:1) microbial carrier on changes in the bacterial microbiome and the development of biofilm in the anaerobic digestion (AD) of confectionery waste, combined with digested sewage sludge as inoculum. The physicochemical properties of the carrier material are presented, with particular focus on its morphological and dispersion characteristics, as well as adsorption and thermal properties. In this respect, the DEP system was found to be a suitable carrier for both mesophilic and thermophilic AD. The evaluation of quantitative and qualitative changes in the genetic diversity of bacterial communities, carried out using next-generation sequencing (NGS), showed that the material has a modifying effect on the bacterial microbiome. While Actinobacteria was the most abundant cluster in the WF-control sample (WF—waste wafers), Firmicutes was the dominant cluster in the digested samples without the carrier (WF-dig.; dig.—digested) and with the carrier (WF + DEP). The same was true for the count of Proteobacteria, which decreased twofold during biodegradation in favor of Synergistetes. The Syntrophomonas cluster was identified as the most abundant genus in the two samples, particularly in WF + DEP. This information was supplemented by observations of morphological features of microorganisms carried out using fluorescence microscopy. The biodegradation process itself had a significant impact on changes in the microbiome of samples taken from anaerobic bioreactors, reducing its biodiversity. As demonstrated by the results of this innovative method, namely the BioFlux microfluidic flow system, the decrease in the number of taxa in the digested samples and the addition of DEP contributed to the microbial adhesion in the microfluidic system and the formation of a stable biofilm.
Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice
Authors: Rodrigues Patrícia Brito , Gomes Giovanni Freitas , Angelim Monara K. S. C. , Souza Gabriela F. , Muraro Stefanie Primon , Toledo-Teixeira Daniel A. , Rattis Bruna Amanda Cruz , Passos Amanda Stephane , Pral Laís Passarielo , de Rezende Rodovalho Vinícius , dos Santos P. Gomes Arilson Bernardo , Matheus Valquíria Aparecida , Antunes André Saraiva Leão Marcelo , Crunfli Fernanda , Antunes Krist Helen , de Souza Ana Paula Duarte , Consonni Sílvio Roberto , Leiria Luiz Osório , Alves-Filho José Carlos , Cunha Thiago M. , Moraes-Vieira Pedro M. M. , Proença-Módena José Luiz , R. Vinolo Marco Aurélio
Published: August 2022

Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected–treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice.
Intraocular RGD-Engineered Exosomes and Active Targeting of Choroidal Neovascularization (CNV)
Authors: Pollalis Dimitrios , Kim Dongin , Nair Gopa Kumar Gopinadhan , Kang Changsun , Nanda Arjun V. , Lee Sun Young
Published: August 2022

Purpose: To assess the transretinal penetration of intravitreally injected retinal multicell-derived exosomes and to develop exosome-based active targeting of choroidal neovascularization (CNV) by bioengineering with ASL, which is composed of a membrane Anchor (BODIPY), Spacer (PEG), and targeting Ligands (cyclic RGD peptide). Methods: Retinal multicell-derived exosomes were recovered from a whole mouse retina using differential ultracentrifugation. Their size, number, and morphology were characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Exosome markers were confirmed using an exosome detection antibody array. Intravitreal injection of fluorescent (PKH-26)-labeled or engineered ASL exosomes (1 × 106 exosomes/μL) were given to the wild-type mouse or laser-induced CNV mouse model. Retinal uptake of exosomes was assessed by in vivo retinal imaging microscopy and histological staining with DAPI, GSA, and anti-integrin αv for retinal sections or choroid/RPE flat mounts. Active targeting of CNV was assessed by comparing retinal uptake between areas with and without CNV and by colocalization analysis of ASL exosomes with integrin αv within CNV. Staining with anti-F4/80, anti-ICAM-1, and anti-GFAP antibodies on retinal sections were performed to identify intracellular uptake of exosomes and immediate reactive retinal gliosis after exosome treatment. Results: An average of 2.1 × 109 particles/mL with a peak size of 140 nm exosomes were recovered. Rapid retinal penetration of intravitreally injected exosomes was confirmed by retinal imaging microscopy at 3 and 24 h post-injection. Intravitreally delivered PKH-26-labeled exosomes reached inner and outer retinal layers including IPL, INL, OPL, and ONL at 1 and 7 days post-injection. Intravitreally injected ASL exosomes were predominantly delivered to the area of CNV including ONL, RPE, and choroid in laser-induced CNV mouse models with 89.5% of colocalization with integrin αv. Part of exosomes was also taken intracellularly to vascular endothelial cells and macrophages. After intravitreal injection, neither naive exosomes nor ASL exosomes induced immediate reactive gliosis. Conclusions: Intravitreally delivered retinal multicell-derived exosomes have good retinal penetration, and ASL modification of exosomes actively targets CNV with no immediate reactive gliosis. ASL exosomes have a great potential to serve as an intraocular drug delivery vehicle, allowing an active targeting strategy.
Rychc Confers Extreme Resistance to Potato virus Y in Potato
Authors: Li Gege , Shao Jingjing , Wang Yuwen , Liu Tengfei , Tong Yuhao , Jansky Shelley , Xie Conghua , Song Botao , Cai Xingkui
Published: August 2022

The Potato virus Y (PVY) is responsible for huge economic losses for the potato industry worldwide and is the fifth most consequential plant virus globally. The main strategies for virus control are to limit aphid vectors, produce virus-free seed potatoes, and breed virus-resistant varieties. The breeding of PVY-resistant varieties is the safest and most effective method in terms of cost and environmental protection. Rychc, a gene that confers extreme resistance to PVY, is from S. chacoense, which is a wild diploid potato species that is widely used in many PVY-resistant breeding projects. In this study, Rychc was fine mapped and successfully cloned from S. chacoense accession 40-3. We demonstrated that Rychc encodes a TIR-NLR protein by stably transforming a diploid susceptible cultivar named AC142 and a tetraploid potato variety named E3. The Rychc conferred extreme resistance to PVYO, PVYN:O and PVYNTN in both of the genotypes. To investigate the genetic events occurring during the evolution of the Rychc locus, we sequenced 160 Rychc homologs from 13 S. chacoense genotypes. Based on the pattern of sequence identities, 160 Rychc homologs were divided into 11 families. In Family 11 including Rychc, we found evidence for Type I evolutionary patterns with frequent sequence exchanges, obscured orthologous relationships and high non-synonymous to synonymous substitutions (Ka/Ks), which is consistent with rapid diversification and positive selection in response to rapid changes in the PVY genomes. Furthermore, a functional marker named MG64-17 was developed in this study that indicates the phenotype with 100% accuracy and, therefore, can be used for marker-assisted selection in breeding programs that use S. chacoense as a breeding resource.
Simulation of Mushroom Nanostructures with Ag Nanoparticles for Broadband and Wide-Angle Superabsorption
Authors: Wu Jinshuang , Ouyang Mingzhao , Yang Bowei , Fu Yuegang
Published: August 2022

Metal nanoparticles (NPs) concentrate the energy of incident photons through plasmon resonance excitation, which allows scattering into a substrate with a high refractive index, and the radiated energy from this excitation significantly increases the optical absorption of the substrate. In this work, the effect of Ag NPs on the absorption capacity of mushroom-nanostructured Si metasurfaces was analyzed using the finite-difference time-domain method. It was observed that the absorbance in the metasurfaces with Ag NPs increased from 90.8% to 98.7% compared with nanostructured Si metasurface without NPs. It was shown that the plasmon resonance effect of Ag NPs enlarged the range of the FP cavity by about 10 times, and the electric field strength E2 increased by about four times through the combination of Ag NP and Si absorbers. Meanwhile, the effect of randomly distributed nanostructures on the absorption properties of Si metasurfaces was simulated. Additionally, the nanostructured surface with Ag NPs was insensitive to angle, which encourages the design of broadband and wide-angle superabsorption nanostructures.
Effect of WC on Microstructure and Wear Resistance of Fe-Based Coating Fabricated by Laser Cladding
Authors: Wei Angang , Tang Yun , Tong Tong , Wan Fang , Yang Shaoshuai , Wang Kaiming
Published: August 2022

As the core component of the wind turbine transmission chain, the wind power gear plays a vital role in the safe and efficient operation of the whole machine. Wind power gears are subjected to varying degrees of wear on their contact surfaces due to alternating load impacts. For wind power gear repair and remanufacturing, laser cladding technology is proposed on the wind power gearbospline shaft. The effect of tungsten carbide (WC) addition on the laser-clad Fe-based coatings was investigated in this study. The morphology and composition of the composite coatings formed with different proportions of WC were studied using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The microhardness and wear resistance were measured with a digital microhardness tester and a wear testing machine, respectively. The coatings were compact with no apparent cracks or pores and the microstructures of the regions above the fusion zone gradually changed from planar crystal to columnar crystal and cellular crystal, while the middle and upper parts of the coating mainly consisted of equiaxed crystals. The microhardness of the coatings gradually increased with the increase of WC content. The coating with 16% WC addition reached a maximum microhardness of 826.2 HV. The increase of WC content improved the wear resistance of the laser-clad Fe-based composite coatings. The wear mechanism of the coatings was mainly abrasive wear, along with slight adhesion wear and oxidative wear.
Realizing Efficient Photoelectrochemical Performance for Well-Designed CdS@ZnIn2S4 Heterostructure Photoanode with Directional Interfacial Charge Transfer Dynamics
Authors: Wu Xianchen , Qian Yu , Lv Gangyang , Long Liyuan , Zhou Yong , Wang Dunhui
Published: August 2022

Designing a heterostructure photoanode with an appropriate band alignment, a beneficial charge migration pathway, and an adequate interfacial coupling is crucial for photoelectrochemical (PEC) energy conversion. Herein, we fabricate a hetero-nanostructure photoanode with CdS nanorods (CdS NRs) and two-dimensional (2D) ZnIn2S4 nanosheets (ZIS NSs) via a two-step in situ growth method on FTO glass to acquire a sufficient interfacial contact between two semiconductors. Based on their electronic band structures, the CdS is designed to be firstly grown on FTO to act as a photoelectron transport layer and 2D ZIS is further fabricated on the CdS as a photohole accumulation layer to directly contact the electrolyte. Benefitting from the Type II band alignment between the CdS and ZIS, such a heterostructure significantly enhances the separation efficiency and prolongs the lifetime of photocarriers. More importantly, it ensures that photoholes accumulate on the 2D ZIS with a highly exposed surface area for an oxidation reaction at the surface-active sites, while the photoelectrons transfer to counter electrode for hydrogen evolution. The optimum CdS@ZIS heterostructure photoanode exhibits a superior PEC performance with a photocurrent of 4.19 mA/cm2 at 1.23 VRHE (two times that of the CdS and eight times that of ZIS) and an applied bias photo-to-current efficiency (ABPE) of 1.93% at 0.49 VRHE. This work can inspire the future design of heterostructure photoanodes for highly efficient solar energy conversion.
Controlling the Polymorphic Outcome of 2,6-Dimethoxybenzoic Acid Crystallization Using Additives
Authors: Semjonova Aina , Bērziņš Agris
Published: August 2022

In this study, 2,6-dimethoxybenzoic acid (2,6MeOBA) was used as a model substance to investigate the use of additives to control the polymorphic outcome of crystallization. 2,6MeOBA exists as three polymorphs. Two of the 2,6MeOBA polymorphs, I and III, obtained in most of the crystallization experiments, were characterized by thermal analysis, and their relative thermodynamic stability was determined. Forms I and III are enantiotropically related, where form III is the high-temperature form. Pure form II was very difficult to obtain. Crystallization of 2,6MeOBA was explored under different conditions by performing evaporation and cooling crystallization from different solvents. Surfactants, polymers, and different molecular compounds with diverse possibilities for the formation of intermolecular interactions were tested as additives. The additives facilitating the crystallization of the metastable forms were additionally studied under different crystallization conditions. The effect of additives polyethylene glycol (PEG) and hydroxypropyl cellulose (HPC) on the thermodynamic stability and solvent-mediated phase transition (SMPT) kinetics was evaluated. HPC and PEG showed the potential to favor the formation of form III in crystallization from water.
Palbociclib Induces the Apoptosis of Lung Squamous Cell Carcinoma Cells via RB-Independent STAT3 Phosphorylation
Authors: Xiang Wenjing , Qi Wanchen , Li Huayu , Sun Jia , Dong Chao , Ou Haojie , Liu Bing
Published: August 2022

Lung squamous cell carcinoma (LUSC) treatment response is poor and treatment alternatives are limited. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients and applied in multiple preclinical models, but its use for LUSC therapy remains elusive. Here, we investigated whether palbociclib induced cell apoptosis and dissected the underlying mechanism in LUSC. We found that palbociclib induced LUSC cell apoptosis through inhibition of Src tyrosine kinase/signal transducers and activators of transcription 3 (STAT3). Interestingly, palbociclib reduced STAT3 signaling in LUSC cells interfered by retinoblastoma tumor-suppressor gene (RB), suggesting that pro-apoptosis effect of palbociclib was independent of classic CDK4/6-RB signaling. Furthermore, palbociclib could suppress IL-1β and IL-6 expression, and therefore blocked Src/STAT3 signaling, which were rescued by either recombinant human IL-1β or IL-6. Moreover, Myc mediated the sensitivity of LUSC cells to palbociclib. Our discoveries demonstrated that palbociclib induces apoptosis of LUSC cells through the Src/STAT3 axis in an RB-independent manner, and provided a reliable experimental basis of clinical studies in LUSC patients.
Impact of Stump Removal on Communities of Ectomycorrhizal and Other Soil Fungi in Norway Spruce Stands of Latvia
Authors: Burnevica Natalija , Klavina Darta , Polmanis Kaspars , Jansons Jurgis , Gaitnieks Talis
Published: August 2022

Heterobasidion root rot is one of the most economically important conifer diseases in the Northern Hemisphere, and stump removal is considered to be one of most effective control methods. However, the impact of stump removal on the diversity of mycorrhizal and soil fungi should be evaluated. From 2011 to 2012, a stump removal trial was established in six different sample plots in two regions of Latvia. The stump removal sites and control sites were replanted with spruce seedlings in 2012. Seven years later, soil samples were collected in the stump removal and control sample plots to compare the diversity of mycorrhizal and soil fungi. Fungal communities were analyzed using next-generation sequencing methods. Our results showed that there are no significant differences in mycorrhizal and soil fungal communities between the stump removal area and the clear-felled control area seven years later. The mycorrhizal fungi were the most commonly sequenced fungal ecological group, and their diversity was similar to clear-felled control sites. However, there were some differences in the fungal species composition.
A European Approach to the Establishment of Data Spaces
Authors: Minghini Marco , Kotsev Alexander , Granell Carlos
Published: August 2022

Within a context defined by the rapid increase in the availability of data, combined with the complexity of data sources, infrastructures, technologies and actors involved in data sharing flows, the European Union (EU) is devising approaches that can reap the benefits of data-driven innovation [...]