bluuebunny/crossref_metadata_2025 huggingface dataset:
Computer classification and construction of a novel prognostic signature based on moonlighting genes in prostate cancer
Authors: Mei Wangli , Jin Liang , Zhang Bihui , Sun Xianchao , Yang Guosheng , Li Sheng , Ye Lin
Published: October 2022

Advanced prostate cancer (PRAD) patients have poor prognosis and rising morbidity despite the ongoing iteration of molecular therapeutic agents. As newly discovered proteins with several functions, Moonlighting proteins have showed an important role in tumor progression but has not been extensively investigated in PRAD. Our study aimed to identify moonlighting-related prognostic biomarkers and prospective PRAD therapy targets. 103 moonlighting genes were gathered from previous literatures. A PRAD classification and multivariate Cox prognostic signature were constructed using dataset from The Cancer Genome Atlas (TCGA). Subsequently, we tested our signature’s potential to predict biochemical failure-free survival (BFFS) using GSE21032, a prostate cancer dataset from Gene Expression Omnibus (GEO). The performance of this signature was demonstrated by Kaplan-Meier (KM), receiver operator characteristic (ROC), areas under ROC curve (AUC), and calibration curves. Additionally, immune infiltration investigation was conducted to determine the impact of these genes on immune system. This signature’s influence on drug susceptibility was examined using CellMiner’s drug database. Both training and validation cohorts demonstrated well predictive capacity of this 9-gene signature for PRAD. The 3-year AUCs for TCGA-PRAD and GSE21032 were 0.802 and 0.60 respectively. It can effectively classify patients into various biochemical recurrence risk groups. These genes were also assessed to be connected with tumor mutation burden (TMB), immune infiltration and therapy. This work created and validated a moonlighting gene signature, revealing fresh perspectives on moonlighting proteins in predicting prognosis and improving treatment of PRAD.
Role of the TSPO–NOX4 axis in angiogenesis in glioblastoma
Authors: Jiang Hongxiang , Li Fei , Cai Linzhi , Chen Qianxue
Published: October 2022

Objective: Angiogenesis is a pathological feature of glioblastoma. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a vital source of reactive oxygen species (ROS) related to angiogenesis. However, signaling pathways correlated with the isoform oxidase are unknown. The aim of this study was to elucidate the detailed mechanism of the role of NOX4 in angiogenesis in glioblastoma.

Methods: Public datasets were searched for studies on immunohistochemistry and western blotting to evaluate NOX4 expression in glioma. The location of NOX4 expression was detected by immunofluorescence. We conducted conditional deletion of the translocator protein (TSPO) targeting the protein with the synthetic ligand XBD173 in the glioblastoma mouse model. NOX4 downregulation was conducted with the NOX4 inhibitor GLX351322, and ROS production and angiogenesis were detected in glioma tissues.

Results: Clinical samples and public datasets showed that NOX4 was upregulated and associated with the prognosis. NOX4 is mainly expressed in endothelial cells of glioblastoma. Both TSPO and NOX4 promoted angiogenesis in an ROS-dependent manner, suggesting that TSPO triggered ROS production in glioblastoma via NOX4.

Conclusion: These results showed that TSPO is an upstream target of NOX4-derived mitochondrial ROS, which is indispensable for NOX4-derived mitochondrial ROS-induced angiogenesis in glioblastoma. TSPO–NOX4 signaling could serve as a molecular target for therapeutic strategies for glioblastoma.
Recombinant phage displaying ToAP2D peptide with antifungal activity against Sporothrix globosa
Authors: Yan Tianyi , An Lin , Chen Feng
Published: October 2022

We designed and synthesized recombinant phage nanofibers displaying ToAP2D peptide and investigated their antifungal effect on Sporothrix and the corresponding mechanism. Antimicrobial peptide, ToAP2D, was used as the template. The effect of synthesized recombinant phages on the immune function of CD4+ T lymphocytes in mice was tested using an enzyme-linked immunosorbent assay. The therapeutic effect and safety of recombinant phage administration on Sporothrix-infected BALB/c mice were evaluated based on survival analysis, histopathological changes, and renal and liver functions. The successfully prepared recombinant phage displaying ToAP2D peptides significantly inhibited Sporothrix growth. According to the scanning electron microscopy results, the recombinant phage caused shrinkage and rupture of Sporothrix globosa, leading to leakage of the contents. The Hoechst/propidium iodide double staining test indicated that the recombinant phage could induce cell apoptosis of Sporothrix globosa. The apoptotic pathway might be due to the accumulation of reactive oxygen species in large quantities in cells, activating caspase dependence; this reduced inflammation, prolonged the survival time, and enhanced levels of IFN-γ and IL-17 in mice. We believe that recombinant phage inhibits Sporothrix growth by adjusting the immune response of mice, inducing Sporothrix apoptosis and improving animal survival. This study offers a new approach to preparing antimicrobial peptides.
Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress
Authors: Zhong Yadi , Chen Yingjian , Pan Zhisen , Tang Kaijia , Zhong Guangcheng , Guo Jingyi , Cui Tianqi , Li Tianyao , Duan Siwei , Yang Xiaoying , Gao Yong , Wang Qi , Zhang Dong
Published: October 2022

Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes. Additionally, Ginsenoside Rc effectively alleviates APAP-induced cellular apoptosis and NAPQI accumulation in MPHs. In vivo, Ginsenoside Rc administration remarkably attenuates APAP-induced hepatotoxicity, repairing liver damage and improving survival. Moreover, Ginsenoside Rc treatment modulates genes involved in APAP metabolism, leading to a decrease in NAPQI and resulting in the alleviation of fatal oxidative stress and inflammatory response after APAP exposure, along with the expression of their related indicators. Furthermore, our RNA-seq and molecular docking analysis implies that FXR expression and FXR transcriptional activity are stimulated by Ginsenoside Rc treatment. Notably, due to the lack of FXR in mice and MPHs, ginsenoside Rc can no longer play its original protective role against hepatotoxicity and cell damage caused by APAP, and it is difficult to improve the corresponding survival rate and prevent hepatic apoptosis, NAPQI generation, fatal oxidative stress, and the inflammatory response induced by APAP and the expression of related genes. In summary, our results indicate that Ginsenoside Rc could act as an effective FXR activator and effectively regulate FXR-induced antioxidant stress and eliminate inflammation while also having an anti-apoptotic function.
Ganfule capsule alleviates bile duct ligation-induced liver fibrosis in mice by inhibiting glutamine metabolism
Authors: Ke Chang , Gao Jianlong , Tu Jiyuan , Wang Yan , Xiao Yangxin , Wu Yuan , Liu Yanju , Zhou Zhongshi
Published: October 2022

Background: Liver fibrosis is a pathological outcome of a variety of liver diseases, and it can also progress into liver cirrhosis and liver cancer. Specific liver antifibrotic drugs have not been clinically approved yet. Studies have demonstrated the protective effects of Ganfule capsule (GFL) on the liver and its therapeutic potential in hepatic cancer. However, the mechanism of GFL is not clear in the treatment of liver fibrosis.

Objective: This article aims to study the protective effect of GFL on liver fibrosis and its possible mechanism.

Methods: The cholestatic liver fibrosis model was prepared by subjecting C57BL/6 mice to bile duct ligation (BDL). The GFL groups were treated with different concentrations of GFL for 14 days. Pathological analysis, serum biochemical index detection, metabonomic analysis, immunohistochemistry, Western blot, and real-time PCR were carried out.

Results: GFL could alleviate liver injury and liver fibrosis caused by BDL in mice. Metabonomic analysis of mice serum showed postoperative metabolic disorder, which could be alleviated by GFL through glutamine metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-tRNA biosynthesis; and other metabolic pathways. GFL affected glutamine metabolism by inhibiting the activity of glutaminase 1 (GLS1). The activation of GLS1 is regulated by the NF-κB pathway, and experiments showed that GFL could inhibit IκB-α and NF-κB p65 phosphorylation.

Conclusion: This study confirms the protective effect of GFL on liver injury and shows that GFL inhibits glutamine metabolism, which was correlated with the NF-κB pathway, and eventually alleviates liver fibrosis. These results are conducive to the development of new therapeutic drugs for liver fibrosis.
Brazilian organic propolis for prevention and treatment of radiation-related oral acute toxicities in head and neck cancer patients: A double-blind randomized clinical trial
Authors: Fernandes Patrícia Maria , Rosalen Pedro Luiz , Fernandes Diego Tetzner , Dias-Neto Emmanuel , Alencar Severino Matias , Bueno-Silva Bruno , Alves Fábio de Abreu , Lopes Márcio Ajudarte
Published: October 2022

Background: Oral mucositis (OM) is one of the most important acute toxicities from radiotherapy (RT) in head and neck cancer patients and can impair oncologic treatment. Dysphagia, dysgeusia, pain, and oral candidiasis are other common toxicities. Brazilian Organic Propolis (BOP) is a recently described propolis variant and BOP types 4 and 6 have shown important antioxidant, anti-inflammatory, and antifungal properties.

Purpose: To investigate the use of BOP as a preventive and/or complementary therapeutic option for radiotherapy-induced oral mucositis, dysphagia, dysgeusia, pain, and oral candidiasis. Additionally, proinflammatory cytokines were assessed to investigate their anti-inflammatory role.

Methods: Sixty patients were included in this randomized, double-blind, controlled clinical trial. Patients were randomized to receive either aqueous suspension of a BOP or placebo throughout RT. Also, all patients underwent low-level laser therapy as routine oral care. OM, dysphagia, and dysgeusia were assessed weekly according to WHO and NCI scales. Pain-related to OM was assessed according to a Visual Analog Scale and the presence or absence of oral candidiasis was checked by intraoral examination. Protein levels of TNF-α and IL-1β from oral mucosa were assessed by ELISA.

Results: Patients in the propolis group had a lower mean score of OM, dysphagia, dysgeusia, and most patients reported moderate pain. Fewer patients developed oral candidiasis in the propolis group, and the number of episodes was lower among patients that used BOP (p < 0.05). In addition, the BOP group presented significantly lower levels of IL-1β since the beginning of treatment when compared with placebo patients (p < 0.05) and a lower level of TNF-α at the end of treatment (p < 0.001).

Conclusion: Topic use of BOP reduced TNF-α and IL-1β levels, oral candidiasis episodes, and seems to be a useful complementary option for the prevention and treatment of the main acute oral toxicities of RT.

Clinical Trial Registration:http://www.ensaiosclinicos.gov.br/rg/RBR-9f8c78/, identifier RBR-9f8c78
SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™
Authors: Saleem Muhammad Talha , Shoaib Muhammad Harris , Yousuf Rabia Ismail , Ahmed Farrukh Rafiq , Ahmed Kamran , Siddiqui Fahad , Mahmood Zafar Alam , Sikandar Muhammad , Imtiaz Muhammad Suleman
Published: October 2022

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.
The role of melatonin in the development of postmenopausal osteoporosis
Authors: Yang Keda , Qiu Xueshan , Cao Lili , Qiu Shui
Published: October 2022

Melatonin is an important endogenous hormone that modulates homeostasis in the microenvironment. Recent studies have indicated that serum melatonin levels are closely associated with the occurrence and development of osteoporosis in postmenopausal women. Exogenous melatonin could also improve bone mass and increase skeletal strength. To determine the underlying mechanisms of melatonin in the prevention and treatment of postmenopausal osteoporosis, we performed this review to analyze the role of melatonin in bone metabolism according to its physiological functions. Serum melatonin is related to bone mass, the measurement of which is a potential method for the diagnosis of osteoporosis. Melatonin has a direct effect on bone remodeling by promoting osteogenesis and suppressing osteoclastogenesis. Melatonin also regulates the biological rhythm of bone tissue, which benefits its osteogenic effect. Additionally, melatonin participates in the modulation of the bone microenvironment. Melatonin attenuates the damage induced by oxidative stress and inflammation on osteoblasts and prevents osteolysis from reactive oxygen species and inflammatory factors. As an alternative drug for osteoporosis, melatonin can improve the gut ecology, remodel microbiota composition, regulate substance absorption and maintain metabolic balance, all of which are beneficial to the health of bone structure. In conclusion, our review systematically demonstrates the effects of melatonin on bone metabolism. Based on the evidence in this review, melatonin will play a more important role in the diagnosis, prevention and treatment of postmenopausal osteoporosis.
Newly discovered circRNAs in rheumatoid arthritis, with special emphasis on functional roles in inflammatory immunity
Authors: Li Zhenyu , Wang Jianpeng , Lin Yudong , Fang Jihong , Xie Kang , Guan Zhiye , Ma Hailong , Yuan Liang
Published: October 2022

Circular RNA (circRNA) is a unique type of endogenous RNA. It does not have free 3 ′or 5′ ends, but forms covalently closed continuous rings. Rheumatoid arthritis (RA) is a common chronic autoimmune joint disease, characterized by chronic inflammation of the joint synovial membrane, joint destruction, and the formation of pannus. Although the pathogenesis of rheumatoid arthritis remains incompletely understood, a growing amount of research shows that circRNA has a close relationship with RA. Researchers have found that abnormally expressed circRNAs may be associated with the occurrence and development of RA. This article reviews the inflammatory immune, functions, mechanisms, and values of the circRNAs in RA to provide new ideas and novel biomarkers for the diagnosis and treatment of RA.
Healthcare professionals’ knowledge, attitude and practice towards National Centralized Drug Procurement policy in central China: A cross-sectional study
Authors: Huang Anqi , Wang Xuanxuan , Tao Yun , Lin Likai , Cheng Hong
Published: October 2022

Background: National Centralized Drug Procurement (NCDP), an ongoing government-led policy starting in 2019 in China, aimed at reducing drug costs. During the implementation of NCDP, healthcare professionals (HCPs) still have a certain degree of concern about the policy, which affects the clinical use of related drugs.

Objective: This study aims to assess the level of knowledge, attitude and practice (KAP) of HCPs towards NCDP policy, together with the associated factors that determine their KAP.

Methods: A cross-sectional study was conducted between September and November of 2021 in 30 hospitals in Hubei province in Central China. A self-designed online questionnaire including KAP towards NCDP policy was administered to HCPs. Logistic regression analysis was adopted to identify the factors associated with KAP.

Results: A Total of, 742 HCPs completed the questionnaires. 43.4% of HCPs had good knowledge, 24.7% had a positive attitude, and 23.7% held good practice. Through multivariate logistic regression analysis, HCPs who are males, pharmacists, with senior professional titles and 6–10 years of professional working experience contributed to a higher knowledge level. Pharmacists and HCPs with good knowledge were more likely to have positive attitudes, while HCPs with higher education were less likely to have positive attitudes. Pharmacists, HCPs who had 11–20 years of professional working experience, worked in medium-size urban areas or had good knowledge were more likely to have good practice. Good practice is also associated with the positive attitude towards the efficacy of centralized-purchased medicines and impacts of NCDP policy.

Conclusion: Only a small percentage of HCPs had good KAP towards NCDP policy. Pharmacists showed better KAP than physicians. The positive attitude towards the efficacy of centralized-purchased medicines and impacts of NCDP policy contributed to better practice. High-quality clinical evidence on the therapeutic effects and safety of the centralized-purchased drugs is needed.
Inefficient intramolecular vibrational energy redistribution for the H + HO2 reaction and negative internal energy dependence for its rate constant
Authors: Jasper Ahren W. , Moberg Daniel R. , Tao Yujie , Klippenstein Stephen J. , Sivaramakrishnan Raghu
Published: October 2022

Quasiclassical trajectories (QCT) and newly constructed global potential energy surfaces are used to compute thermal and nonthermal rate constants for the H + HO2 reaction. The thermal QCTs rate constants are up to 50% smaller than transition state theory (TST) rate constants based on the same level of electronic structure theory. This reduction is demonstrated to result from inefficient intramolecular vibrational energy redistribution (IVR) in the transient H2O2 well, with a significant fraction of trajectories that reach the H2O2 well promptly dissociating back to reactants instead of via the heavily statistically favored 2OH channel. The nonstatistical reduction factor, κIVR, that quantifies this effect is shown to increase in importance with temperature, with κIVR = 0.81 at 300 K and 0.47 at 2500 K. Finally, we show that inefficient IVR causes H + HO2 rate constants mediated by H2O2 to depend inversely on the initial vibrational excitation of HO2.
Kerr nonlinearity-assisted quadratic microcomb
Authors: Wang Ke , Li Jing , Dai Fan , Wang Mengshuai , Wang Chuanhang , Wang Qiang , Tu Chenghou , Li Yongnan , Wang Hui-Tian
Published: October 2022

Generation of nonlinear frequency combs in χ(3) optical microresonators has attracted tremendous research interest during the last decade. Recently, realization of the microcomb owing to χ(2) optical nonlinearity in the microresonator promises new breakthroughs and is a big scientific challenge. Moreover, it is of high scientific interest that the presence of both second- and third-order nonlinearities results in complex cavity dynamics. In particular, the role of χ(3) nonlinearity in the generation of the quadratic microcomb is still far from being well understood. Here, we demonstrate the interaction between the second- and third-order nonlinearity in the lithium niobate microresonator, which can provide a new way of phase matching to control the mode-locking condition and pulse number for the quadratic microcomb. Our results verify that the Kerr nonlinearity can benefit the quadratic microcomb. The principle can be further extended to other material platforms to provide more manipulation methods for comb generation based on χ(2) nonlinearity at mid-infrared.
Study on flow characteristics of natural gas containing CO2 invading wellbore during drilling
Authors: He Haikang , Sun Baojiang , Sun Xiaohui , Li Xuefeng , Shan Zhengfeng
Published: October 2022

The dissolution of invaded gas in the drilling fluid during drilling results in an increase in the gas invasion concealment. This is of great significance for the development of acid gas reservoirs to determine the solubility change and multiphase flow law in an annulus after invasion by natural gas with high CO2 content. In this study, control equations of gas–liquid flow during drilling gas invasion are established considering the influence of gas solubility. For the prediction of gas solubility, the interaction parameters of CH4 and water in the Peng–Robinson equation of state are optimised to establish a gas solubility prediction model. The solubility of natural gas with high CO2 content in water and brine solution is measured through phase-equilibrium experiments. The results indicate that the newly optimised solubility model can accurately predict the solubility of CH4 and CO2 in water, and the prediction error is within 5%. Moreover, the prediction error for the solubility of CH4 and CO2 mixed gas is within 15%. The analysis of gas invasion in example engineering drilling applications reveals that an increase in the CO2 content in the invaded gas leads to a slow change in the mud-pit increment, and the concealment strengthens as the distance between the gas-migration front and the wellhead increases. Gas solubility has a significant impact on the monitoring of gas invasion in low permeability reservoirs.
Generation of h–Shaped pulse in a mode–Locked erbium-doped fiber laser
Authors: Liu Chao , Li Guoru , Su Xiancui , Wang Yiran , Gao Feilong , Xie Yiyan , Kumar Santosh , Zhang Bingyuan
Published: October 2022

In this paper, the generation of h-shaped pulse is demonstrated in a nonlinear polarization rotation mode-locked erbium-doped fiber laser (MLEDFL). The length of the entire cavity is about 2506 m to enhance the nonlinear effect in the cavity. The multi-pulse state is obtained firstly under the certain pump power and polarization state. By further adjusting the polarization controller the h-shaped pulse with sharp top and flat bottom is generated under the pump power of ∼100 mW. And the duration of pulse is tuned with a range of 54.63–470 ns. The width and intensity of pulse trailing part vary differently during the process of increasing pulse width. The results indicate that the peak power clamping effect and weak birefringence effect dominate in different h-shaped pulse forming process.
Modeling of a retarding potential analyzer and comparison with Express-A in-flight measurements
Authors: Nicolle L. , Sarrailh P. , Garrigues L. , Hess S. , Villemant M.
Published: October 2022

In-flight data from the retarding potential analyzers (RPAs) on the Russian geostationary telecommunication satellite Express-A #3 are used to validate electric thruster plume simulations. The RPAs placed on the solar array have made it possible to measure ion properties, current densities, and ion energy distribution functions (IEDFs) at different distances and field-of-view configurations with regard to the thrusters. The present work shows that the conventional probe theory used to interpret measurements is only valid if the probe is oriented toward the thruster. In most Express-A #3 measurements, this is not the case, and it leads to incorrect interpretations. In this study, a new RPA probe model is presented. It enables the physics of a tilted probe to be described more accurately, taking into account the view angle between the RPA entrance surface normal relative to the incoming flux direction, the flux direction nonaligned with the collection surface normal, the internal RPA electric fields, and masking effects due to RPA walls. This probe model is coupled with a simple model for ion transport from an electric thruster source to the probe to allow a comparison with in-flight data. The comparison between Express-A #3 RPA collected currents and calculations from the new model discriminates true ion energy shift from probe misorientation effects. It also shows that highly tilted RPA measurements that were previously never interpreted can be understood and analyzed.
A high resolution γ-ray array for the pandora plasma trap
Authors: Goasduff A. , Santonocito D. , Menegazzo R. , Capra S. , Pullia A. , Raniero W. , Rosso D. , Toniolo N. , Zago L. , Naselli E. , Napoli D. R.
Published: October 2022

The measurement of β-decay rates in plasma, simulating stellar-like conditions, is of high interest for the investigation of radionuclides involved in nuclear astrophysics processes. In the new PANDORA plasma trap, to be built at the INFN—Laboratori Nazionali del Sud of Catania (Italy), the β-decay rates will be estimated by detecting the γ-rays emitted by the daughter nuclei trapped in the confined plasma. The present work describes the high efficiency High Purity Germanium (HPGe) detector array that will be placed around the magnetic trap for this purpose, as well as the front-end electronics and acquisition system suitable for the array operation in presence of a high counting rate background originating from Bremsstrahlung radiation.
Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation
Authors: He Manlin , Feng Lan , Chen Yang , Gao Bin , Du Yiwei , Zhou Lu , Li Fei , Liu Hongbao
Published: October 2022

The activation of Yes-associated protein (YAP) pathway is mutually causal with the increase of extracellular matrix (ECM) stiffness. Polydatin (PD) has been proved to have anti-fibrosis effect in diabetic kidney disease (DKD), but it is still a mystery whether PD participates in YAP-related mechano-transduction. Therefore, this study intends to solve the following two problems: 1) To construct an in vitro system of polyacrylamide hydrogels (PA gels) based on the true stiffness of kidneys in healthy and DKD rats, and observe the effect of PD on pathological matrix stiffness-induced YAP expression in renal fibroblasts; 2) Compared with verteporfin (VP), a pharmacological inhibitor of YAP, to explore whether the therapeutic effect of PD on DKD in vivo model is related to the regulation of YAP. In this study, the in vitro system of PA gels with 3 kPa, 12 kPa and 30 kPa stiffness was constructed and determined for the first time to simulate the kidney stiffness of healthy rats, rats with DKD for 8 weeks and 16 weeks, respectively. Compared with the PA gels with 3 kPa stiffness, the PA gels with 12 kPa and 30 kPa stiffness significantly increased the expression of YAP, α-smooth muscle actin (α-SMA) and collagen I, and the production of reactive oxygen species (ROS) in renal fibroblasts, and the PA gels with 30 kPa stiffness were the highest. PD significantly inhibited the above-mentioned changes of fibroblasts induced by pathological matrix stiffness, suggesting that the inhibition of PD on fibroblast-to-myofibroblast transformation and ECM production was at least partially associated with regulating YAP-related mechano-transduction pathway. Importantly, the inhibitory effect of PD on YAP expression and nuclear translocation in kidneys of DKD rats is similar to that of VP, but PD is superior to VP in reducing urinary protein, blood glucose, blood urea nitrogen and serum creatinine, as well as decreasing the expression of α-SMA and collagen I, ROS overproduction and renal fibrosis. Our results prove for the first time from the biomechanical point of view that PD is a potential therapeutic strategy for delaying the progression of renal fibrosis by inhibiting YAP expression and nuclear translocation.
Crop yield and water use efficiency in response to long-term diversified crop rotations
Authors: Cui Zhengjun , Yan Bin , Gao Yuhong , Wu Bing , Wang Yifan , Xie Yaping , Xu Peng , Wang Haidi , Wen Ming , Wang Yingze , Ma Xingkang
Published: October 2022

Crop production and water productivity may be impacted by diverse crop rotation and management practices. A field study was conducted from 2017-2020 in the Loess Plateau to evaluate the effects of crop rotation sequences on pre-planting and post-harvest soil water storage (SWS), annualized crop yield, water use, and water productivity. Crops in rotation included oil flax (Linum usitatissimum L.) (F), wheat (Triticum aestivum L.) (W), potato (Solanum tuberosum L.) (P). Twelve 4-year-cycle crop rotation treatments, along with a continuous oil flax treatment as a baseline, were included. The results showed that the average soil water content under the 0-150 cm soil layer in all treatments was increased after one rotation cycle, and the PWFW treatment achieved the highest SWC (17.1%). The average soil water storage (winter fallow season) and evapotranspiration (ETa) (growing season) under different crop rotation sequences were lower than those under continuous oil flax cropping. The ETa of FFFF increased by 28.9, 2.7, 15.3, and 28.4%, compared to average crop rotations in 2017, 2018, 2019, and 2020, respectively. Crop rotation had a significant effect on average annual yield and water use efficiency (WUE), which varied by year and rotation sequence. The crop rotations with the highest grain yield of oil flax were FFWP (2017), WFWP (2018),WPFF (2019) and FWPF (2020); the grain yield of wheat was highest when the two pre-crops (previously cultivated crops) were F-F, and potato yield was highest when the two pre-crops were W-F (except 2018). On average, the WUE of oil flax was 8.6, 38.7, 22.7, and 42.1% lower with FFFF than other diversity crop rotations in 2017, 2018, 2019, and 2020. We found that the WUE was not the largest when the grain yield of oil flax and wheat was highest. The treatments with maximum grain yield and WUE were not consistent. Our findings also revealed that wheat-potato-oil flax or potato-wheat-oil flax rotation could increase oil flax grain yields while wheat-oil flax-potato-oil flax markedly improved oil flax WUE.
Population genetic structure of Wikstroemia monnula highlights the necessity and feasibility of hierarchical analysis for a highly differentiated species
Authors: Zhang Chaoqiang , Tang Yiwei , Tian Defeng , Huang Yanyan , Yang Guanghui , Nan Peng , Wang Yuguo , Li Lingfeng , Song Zhiping , Yang Ji , Zhong Yang , Zhang Wenju
Published: October 2022

Population genetic structure can provide valuable insights for conserving genetic resources and understanding population evolution, but it is often underestimated when using the most popular method and software, STRUCTURE and delta K, to assess. Although the hierarchical STRUCTURE analysis has been proposed early to overcome the above potential problems, this method was just utilized in a few studies and its reliability needs to be further tested. In this study, the genetic structure of populations of Wikstroemia monnula was evaluated by sequencing 12 nuclear microsatellite loci of 905 individuals from 38 populations. The STRUCTURE analysis suggested the most likely number of clusters was two, but using multi-hierarchical structure analysis, almost every population was determined with an endemic genetic component. The latter result is consistent with the extremely low gene flow among populations and a large number of unique cpDNA haplotypes in this species, indicating one level of structure analysis would extremely underestimate its genetic component. The simulation analysis shows the number of populations and the genetic dispersion among populations are two key factors to affect the estimation of K value using the above tools. When the number of populations is more than a certain amount, K always is equal to 2, and when a simulation only includes few populations, the underestimation of K value also may occur only if these populations consist of two main types of significantly differentiated genetic components. Our results strongly support that the hierarchical STRUCTURE analysis is necessary and practicable for the species with lots of subdivisions.
A novel locus conferring resistance to Puccinia hordei maps to the genomic region corresponding to Rph14 on barley chromosome 2HS
Authors: Mehnaz Mehnaz , Dracatos Peter M. , Dinh Hoan X. , Forrest Kerrie , Rouse Matthew N. , Park Robert F. , Singh Davinder
Published: October 2022

Barley leaf rust (BLR), caused by Puccinia hordei, is best controlled through genetic resistance. An efficient resistance breeding program prioritizes the need to identify, characterize, and map new sources of resistance as well as understanding the effectiveness, structure, and function of resistance genes. In this study, three mapping populations were developed by crossing Israelian barley lines “AGG-396,” “AGG-397,” and “AGG-403” (carrying unknown leaf rust resistance) with a susceptible variety “Gus” to characterize and map resistance. Genetic analysis of phenotypic data from rust testing F3s with a P. hordei pathotype 5457 P+ revealed monogenic inheritance in all three populations. Targeted genotyping-by-sequencing of the three populations detected marker trait associations in the same genomic region on the short arm of chromosome 2H between 39 and 57 Mb (AGG-396/Gus), 44 and 64 Mb (AGG-397/Gus), and 31 and 58 Mb (AGG-403/Gus), suggesting that the resistance in all three lines is likely conferred by the same locus (tentatively designated RphAGG396). Two Kompetitive allele-specific PCR (KASP) markers, HvGBSv2-902 and HvGBSv2-932, defined a genetic distance of 3.8 cM proximal and 7.1 cM distal to RphAGG396, respectively. To increase the marker density at the RphAGG396 locus, 75 CAPS markers were designed between two flanking markers. Integration of marker data resulted in the identification of two critical recombinants and mapping RphAGG396 between markers- Mloc-28 (40.75 Mb) and Mloc-41 (41.92 Mb) narrowing the physical window to 1.17 Mb based on the Morex v2.0 reference genome assembly. To enhance map resolution, 600 F2s were genotyped with markers- Mloc-28 and Mloc-41 and nine recombinants were identified, placing the gene at a genetic distance of 0.5 and 0.2 cM between the two markers, respectively. Two annotated NLR (nucleotide-binding domain leucine-rich repeat) genes (r2.2HG0093020 and r2.2HG0093030) were identified as the best candidates for RphAGG396. A closely linked marker was developed for RphAGG396 that can be used for marker-assisted selection.
Patient engagement in the development of CF-CBT: A cystic fibrosis-specific cognitive-behavioral intervention for adults
Authors: Friedman Deborah , Kaskas Maysa M. , Quittner Alexandra L. , Smith Beth A. , Georgiopoulos Anna M.
Published: October 2022

Individuals with cystic fibrosis (CF) are at high risk for depression and anxiety, with negative consequences for health and quality of life. Cystic Fibrosis Foundation/European Cystic Fibrosis Society guidelines recommend routine screening, treatment, and preventative efforts. Cognitive-behavioral therapy (CBT) has a large evidence-base for depression/anxiety prevention and treatment. However, traditional CBT protocols require adaptation to address the emotional challenges of coping with CF, stressors related to disease management, and barriers to access to care. The goal of this study was to partner with the CF community to develop an innovative CBT-based intervention for the prevention and treatment of depression and anxiety tailored to CF-specific needs. In-depth feedback was collected via audio-recorded telephone interviews with 16 adults with CF from 3 U.S. CF centers, with purposive sampling across gender, age, ethnicity, and disease severity. A semi-structured interview guide elicited discussion of patient experiences of coping with CF, and perspectives on the acceptability of the content, structure, and delivery model of the proposed intervention. Qualitative analysis utilized a content analytic approach. Participants ranged from 21 to 53 years (M = 35); eight were female; three were Hispanic. Patient-reported most recent FEV1, a measure of lung function based on forced expiratory volume in in one second, ranged from 25 to 113% predicted (M = 72). One participant was post-double lung transplant. Qualitative interviews were analyzed thematically revealing core themes related to the experience of coping with CF. The most frequently cited CF-related stressors were Treatment Burden, Illness Uncertainty, and Financial/Insurance Stress. Participants talked about the interaction of physical symptoms and emotional distress in their daily lives, a topic not typically discussed in routine CF care. Resilience was also a major theme with participants describing strategies they use to cope with CF and hospitalizations. Description of patients’ experiences was incorporated into the program’s intervention manual and patient workbook. Participants also provided direct feedback on the proposed program. Feedback was largely positive regarding program content and structure, suggesting the acceptability of a CF-specific CBT-based intervention for adults with CF. Features to increase accessibility of care including telehealth, inpatient delivery, and team-based care were perceived as advantageous, and participants emphasized the value of a CF-specific mental health intervention. Qualitative findings directly informed the development of CF-CBT, a cognitive-behavioral skills-based program to promote emotional well-being for adults with CF.
Self-organized Learning from Synthetic and Real-World Data for a Humanoid Exercise Robot
Authors: Duczek Nicolas , Kerzel Matthias , Allgeuer Philipp , Wermter Stefan
Published: October 2022

We propose a neural learning approach for a humanoid exercise robot that can automatically analyze and correct physical exercises. Such an exercise robot should be able to train many different human partners over time and thus requires the ability for lifelong learning. To this end, we develop a modified Grow-When-Required (GWR) network with recurrent connections, episodic memory and a novel subnode mechanism for learning spatiotemporal relationships of body movements and poses. Once an exercise is successfully demonstrated, the information of pose and movement per frame is stored in the Subnode-GWR network. For every frame, the current pose and motion pair is compared against a predicted output of the GWR, allowing for feedback not only on the pose but also on the velocity of the motion. Since both the pose and motion depend on a user’s body morphology, the exercise demonstration by one individual cannot easily be used as a reference for further users. We allow the GWR to grow online with each further demonstration. The subnode mechanism ensures that exercise information for individual humans is stored and retrieved correctly and is not forgotten over time. In the application scenario, a physical exercise is performed in the presence of an expert like a physiotherapist and then used as a reference for a humanoid robot like Pepper to give feedback on further executions of the same exercise. For evaluation, we developed a new synthetic exercise dataset with virtual avatars. We also test our method on real-world data recorded in an office scenario. Overall, we claim that our novel GWR-based architecture can use a learned exercise reference for different body variations through incremental online learning while preventing catastrophic forgetting, enabling an engaging long-term human-robot experience with a humanoid robot.
Recent progress in theory and observational study of dust grain alignment and rotational disruption in star-forming regions
Authors: Tram Le Ngoc , Hoang Thiem
Published: October 2022

Modern understanding of dust astrophysics reveals that radiative torques (RATs) arising from the radiation–dust interaction can induce two fundamental effects: grain alignment and rotational disruption. Here, we review the recent progress in the theoretical development and observational testing of these effects using dust polarization observed toward star-forming regions (SFRs). We first review the basic theory of the RAT alignment and RAT disruption, which are referred to as RAT-A and RAT-D effects, respectively. We then briefly describe the numerical method used to model polarized thermal dust emission by accounting for both RAT-A and RAT-D and theoretical predictions of dust polarization for observations. Next, we review our observational efforts to search for observational evidence of the RAT-A and RAT-D effects using thermal dust polarization toward SFRs. Finally, we discuss magnetic fields inferred from dust polarization observed toward these SFRs and implications of the RAT paradigm for different astrophysical conditions, including protostellar environments, dust evolution, and time-domain astrophysics.
Forward modelling and the quest for mode identification in rapidly rotating stars
Authors: Mirouh Giovanni M.
Published: October 2022

Asteroseismology has opened a window on the internal physics of thousands of stars, by relating oscillation spectra properties to the internal physics of stars. Mode identification, namely the process of associating a measured oscillation frequency to the corresponding mode geometry and properties, is the cornerstone of this analysis of seismic spectra. In rapidly rotating stars this identification is a challenging task that remains incomplete, as modes assume complex geometries and regular patterns in frequencies get scrambled under the influence of the Coriolis force and centrifugal flattening. In this article, I will first discuss the various classes of mode geometries that emerge in rapidly rotating stars and the related frequency and period patterns, as predicted by ray dynamics, complete (non-)adiabatic calculations, or using the traditional approximation of rotation. These patterns scale with structural quantities and help us derive crucial constraints on the structure and evolution of these stars. I will summarize the amazing progress accomplished over the last few years for the deciphering of gravity-mode pulsator oscillation spectra, and recent developments based on machine-learning classification techniques to distinguish oscillation modes and pattern analysis strategies that let us access the underlying physics of pressure-mode pulsators. These approaches pave the way to ensemble asteroseismology of classical pulsators. Finally, I will highlight how these recent progress can be combined to improve forward seismic modelling. I will focus on the example of Rasalhague, a well-known rapid rotator, to illustrate the process and the needed advances to obtain à-la-carte modelling of such stars.
Neutron-capture measurement candidates for the r-process in neutron star mergers
Authors: Vescovi Diego , Reifarth René , Cristallo Sergio , Couture Aaron
Published: October 2022

Neutron star mergers (NSMs) are one of the astrophysical sites for the occurrence of the rapid neutron capture process (r-process). After a merger, the ejected neutron-rich matter hosts the production of radioactive heavy nuclei located far from the stability valley. Their nuclear physics properties are key inputs for r-process nucleosynthesis calculations. Here, we focus on the importance of neutron-capture rates and perform a sensitivity study for typical outflows from NSMs. We identify the rates with the highest impact on the final r-process abundance pattern and the nuclear energy release, therefore determining the nucleosynthesis in NSMs. A list of major n-capture rates affecting individual isotopes and elements production is also provided.
Developmental Programming of Fertility in Cattle—Is It a Cause for Concern?
Authors: Wathes D. Claire
Published: October 2022

Cattle fertility remains sub-optimal despite recent improvements in genetic selection. The extent to which an individual heifer fulfils her genetic potential can be influenced by fetal programming during pregnancy. This paper reviews the evidence that a dam’s age, milk yield, health, nutrition and environment during pregnancy may programme permanent structural and physiological modifications in the fetus. These can alter the morphology and body composition of the calf, postnatal growth rates, organ structure, metabolic function, endocrine function and immunity. Potentially important organs which can be affected include the ovaries, liver, pancreas, lungs, spleen and thymus. Insulin/glucose homeostasis, the somatotropic axis and the hypothalamo-pituitary-adrenal axis can all be permanently reprogrammed by the pre-natal environment. These changes may act directly at the level of the ovary to influence fertility, but most actions are indirect. For example, calf health, the timing of puberty, the age and body structure at first calving, and the ability to balance milk production with metabolic health and fertility after calving can all have an impact on reproductive potential. Definitive experiments to quantify the extent to which any of these effects do alter fertility are particularly challenging in cattle, as individual animals and their management are both very variable and lifetime fertility takes many years to assess. Nevertheless, the evidence is compelling that the fertility of some animals is compromised by events happening before they are born. Calf phenotype at birth and their conception data as a nulliparous heifer should therefore both be assessed to avoid such animals being used as herd replacements.