bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of resveratrol on rheumatoid arthritis: From bench to bedside
Authors: Sheng Shuyan , Wang Xinyi , Liu Xin , Hu Xinyang , Shao Yubao , Wang Gaoyuan , Mao Deshen , Li Conghan , Chen Bangjie , Chen Xiaoyu
Published: August 2022

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by symmetrical polyarthritis as its main clinical manifestation. Uncontrolled RA eventually leads to joint deformities and loss of function. Currently, the pathogenesis of RA remains under discussion, and RA treatment is still at the bottleneck stage. Resveratrol has long been regarded as a potential antioxidant drug for RA treatment. Currently, resveratrol is considered to exert therapeutic effects on RA by activating silent information regulator 1 (SIRT1) and its downstream pathways. There is notable crosstalk between the SIRT1 and NF-κB pathways, and these pathways, which play an essential role in the development of RA, are unexpectedly linked to the influence of resveratrol. Based on recent studies of almost all the pathways that resveratrol can affect, this review summarizes a regulatory chain of core components that cover multiple tracks. We also list the effects of resveratrol on immune cells and other subtle controls, which can help clinicians understand the known mechanism of resveratrol and better treat patients with RA.
Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
Authors: Wang Dunfang , Han Jiayin , Pan Chen , Li Chunying , Zhao Yong , Liu Suyan , Zhang Yushi , Tian Jingzhuo , Yi Yan , Zhu Jingjing , Liu Chenyue , Wang Yuan , Xian Zhong , Meng Jing , Qin Shasha , Tang Xuan , Wang Fang , Liang Aihua
Published: August 2022

Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hyperpermeability and exudative inflammation. However, the chief culprits and underlying mechanisms involved in penicillin-induced NAHRs have not yet been fully elucidated. In this study, we used a combination of approaches including a mouse non-allergic hypersensitivity reaction model, UPLC-MS/MS analyses of arachidonic acid metabolites (AAMs), immunoblotting technique, and molecular docking, etc to investigate the culprits involved in penicillin-induced hypersensitivity reactions. We found penilloic acid, one of the main MIs of penicillin, could trigger NAHRs via inducing increased vascular permeability, while the other MIs did no exhibit similar effect. Penilloic acid-induced reactions were not IgE-dependent. Significantly increased arachidonic acids and cascade metabolites in lungs, and activation of RhoA/ROCK signaling pathway in the ears and lungs of mice were noticed after once administration of penilloic acid. This study revealed that penilloic acid was the chief culprit involved in penicillin-induced immediate NAHRs in mice, which mainly associated with direct stimulation of vascular hyperpermeability and exudative inflammation. The activations of AAMs and RhoA/ROCK signaling pathway played important roles in these reactions.
Adverse drug reactions and correlations with drug–drug interactions: A retrospective study of reports from 2011 to 2020
Authors: Jiang Huaqiao , Lin Yanhua , Ren Weifang , Fang Zhonghong , Liu Yujuan , Tan Xiaofang , Lv Xiaoqun , Zhang Ning
Published: August 2022

Introduction: Adverse drug reactions (ADRs) represent a public health problem worldwide that deserves attention due to the impact on mortality, morbidity, and healthcare costs. Drug–drug interactions (DDIs) are an important contributor to ADRs. Most of the studies focused only on potential DDIs (pDDIs), while the detailed data are limited regarding the ADRs associated with actual DDIs.

Methods: This retrospective study evaluated ADRs reported between 2011 and 2020 in a tertiary hospital. The causality and severity of ADRs were evaluated through the Naranjo Algorithm and Hartwig’s scale, respectively. Preventability classification was based on the modified Schoumock and Thornton scale. For ADRs with at least two suspected drugs, pDDIs were identified according to the Lexi-Interact. We further checked whether the ADR description in the reports corresponded to the clinical consequences of the pDDIs.

Results: A total of 1,803 ADRs were reported, of which 36.77% ADRs were classified as mild, 43.26% as moderate, and 19.97% as severe. The assessment of causality showed that the distributions of definite, probable, and possible categories were 0.33%, 58.68%, and 40.99%, respectively. A total of 53.97% of ADRs were identified as preventable ADRs, while 46.03% were recognized as unpreventable. The severity of ADRs was significantly correlated with age, the number of suspected drugs and preventability. Antimicrobial agents were the most common implicated pharmacological group, and the most frequently affected system was the gastrointestinal system. Considering individual drugs, aspirin was the most frequently reported drug. Among 573 ADRs with at least two suspected drugs, 105 ADRs were caused by actual DDIs, of which only 59 and 6 ADRs were caused by actual DDIs in category D and X, respectively. The most frequent drugs involved in actual DDIs of category D were aspirin and heparin, with the majority of ADRs being gastrointestinal bleeding.

Conclusion: This study analyzed the pattern of ADRs in detail and obtained clinical evidence about ADRs associated with actual DDIs. These findings may be useful to compare patterns between different centers and to design preventive strategies for ADRs. Continuous education and training should be provided for physicians regarding the knowledge and recognition of ADRs associated with DDIs.
Total flavonoids of hawthorn leaves protect spinal motor neurons via promotion of autophagy after spinal cord injury
Authors: Zhang Qiong , Liu Mingfu , Nong Haibin , Zhang Yanan , Bai Yiguang , Liu Pan , Zong Shaohui , Zeng Gaofeng
Published: August 2022

The death of spinal motor neurons (SMNs) after spinal cord injury (SCI) is a crucial cause, contributing to a permanent neurological deficit. Total flavonoids of hawthorn leaves (TFHL) have been confirmed to have potentially therapeutic for SCI. Nonetheless, the roles and mechanisms of TFHL in recovering neuromotor function and regenerating axons of SMNs have not been fully elucidated. In this study, TFHL was applied to treat rats with SCI and injured SMNs for 7 days. In vivo experiment, rats with SCI were evaluated by a BBB (Basso-Beattie-Bresnahan) score to assess their motor functional recovery. The morphology, microstructure, apoptosis, Nissl bodies, and autophagy of SMNs in spinal cord tissue were detected by Hematoxylin-eosin (HE) staining, transmission electron microscopy, TUNEL staining, Nissl staining, and immunohistochemistry respectively. In vitro experiment, the co-culture model of SMNs and astrocytes was constructed to simulate the internal environment around SMNs in the spinal cord tissue. The cell morphology, microstructure, axonal regeneration, and autophagy were observed via optical microscope, transmission electron microscopy, and immunofluorescence. The content of neurotrophic factors in the cell culture medium of the co-culture model was detected by ELISA. Moreover, the expression of axon-related and autophagy-related proteins in the spinal cord tissue and SMNs was measured by Western Blot. We demonstrated that TFHL improved the neuromotor function recovery in rats after SCI. We then found that TFHL significantly promoted injured spinal cord tissue repair, reduced apoptosis, and improved the functional status of neurons in spinal cord tissue in vivo. Meanwhile, the cell morphology, microstructure, and axonal regeneration of damaged SMNs also obviously were improved, and the secretion of neurotrophic factors was facilitated after treatment with TFHL in vitro. Further, we revealed that TFHL promoted autophagy and related protein expression in vivo and vitro. Taken together, our study suggested that TFHL might facilitate autophagy and have neuroprotective properties in SMNs to enhance the recovery of neuromotor function of rats with SCI.
Diallyl Disulfide: A Bioactive Garlic Compound with Anticancer Potential
Authors: Mitra Saikat , Das Rajib , Emran Talha Bin , Labib Rafiuddin Khan , Noor-E-Tabassum  , Islam Fahadul , Sharma Rohit , Ahmad Islamudin , Nainu Firzan , Chidambaram Kumarappan , Alhumaydhi Fahad A. , Chandran Deepak , Capasso Raffaele , Wilairatana Polrat
Published: August 2022

Cancer is a life-threatening disease caused by the uncontrolled division of cells, which culminates in a solid mass of cells known as a tumor or liquid cancer. It is the leading cause of mortality worldwide, and the number of cancer patients has been increasing at an alarming rate, with an estimated 20 million cases expected by 2030. Thus, the use of complementary or alternative therapeutic techniques that can help prevent cancer has been the subject of increased attention. Garlic, the most widely used plant medicinal product, exhibits a wide spectrum of biological activities, including antibacterial, hypo-lipidemic, antithrombotic, and anticancer effects. Diallyl disulfide (DADS) is a major organosulfur compound contained within garlic. Recently, several experimental studies have demonstrated that DADS exhibits anti-tumor activity against many types of tumor cells, including gynecological cancers (cervical cancer, ovarian cancer), hematological cancers (leukemia, lymphoma), lung cancer, neural cancer, skin cancer, prostate cancer, gastrointestinal tract and associated cancers (esophageal cancer, gastric cancer, colorectal cancer), hepatocellular cancer cell line, etc. The mechanisms behind the anticancer action of DADS include epithelial-mesenchymal transition (EMT), invasion, and migration. This article aims to review the available information regarding the anti-cancer potential of DADS, as well as summarize its mechanisms of action, bioavailability, and pharmacokinetics from published clinical and toxicity studies.
Cell-cycle and apoptosis related and proteomics-based signaling pathways of human hepatoma Huh-7 cells treated by three currently used multi-RTK inhibitors
Authors: Ren Xuejiao , Zhang Qingning , Guo Wenyan , Wang Lan , Wu Tao , Zhang Wei , Liu Ming , Kong Dezhi
Published: August 2022

Sorafenib, lenvatinib and regorafenib, the multi-RTK inhibitors with potent anti-angiogenesis effects, are currently therapeutic drugs generally recommended for the patients with advanced hepatocellular carcinoma (HCC). To date, however, there have been no published studies on the mechanism underling differential effects of the three drugs on HCC cell proliferation, and the proteomic analysis in HCC cell lines treated by regorafenib or lenvatinib. The present study for the first time performed a direct comparison of the cell cycle arrest and apoptosis induction in the Huh-7 cells caused by sorafenib, regorafenib and lenvatinib at respective IC50 using flow cytometry technique, as well as their pharmacological interventions for influencing whole cell proteomics using tandem mass tag-based peptide-labeling coupled with the nLC-HRMS technique. Sorafenib, regorafenib and lenvatinib at respective IC50 drove the remaining surviving Huh-7 cells into a G0/G1 arrest, but lenvatinib and regorafenib were much more effective than sorafenib. Lenvatinib produced a much stronger induction of Huh-7 cells into early apoptosis than sorafenib and regorafenib, while necrotic cell proportion induced by regorafenib was 2.4 times as large as that by lenvatinib. The proteomic study revealed 419 proteins downregulated commonly by the three drugs at respective IC50. KEGG pathway analysis of the downregulated proteins indicated the ranking of top six signaling pathways including the spliceosome, DNA replication, cell cycle, mRNA surveillance, P53 and nucleotide excision repair involved in 33 proteins, all of which were directly related to their pharmacological effects on cell cycle and cell apoptosis. Notably, lenvatinib and regorafenib downregulated the proteins of PCNA, Cyclin B1, BCL-xL, TSP1, BUD31, SF3A1 and Mad2 much more strongly than sorafenib. Moreover, most of the proteins in the P53 signaling pathway were downregulated with lenvatinib and regorafenib by more than 36% at least. In conclusion, lenvatinib and regorafenib have much stronger potency against Huh-7 cell proliferation than sorafenib because of their more potent effects on cell cycle arrest and apoptosis induction. The underling mechanism may be at least due to the 33 downregulated proteins centralizing the signal pathways of cell cycle, p53 and DNA synthesis based on the present proteomics study.
Influence of the gut microbiota on endometriosis: Potential role of chenodeoxycholic acid and its derivatives
Authors: Li Yangshuo , Wang Kaili , Ding Jie , Sun Shuai , Ni Zhexin , Yu Chaoqin
Published: August 2022

The gut microbiota (GM) has received extensive attention in recent years, and its key role in the establishment and maintenance of health and in the development of diseases has been confirmed. A strong correlation between the GM and the progression of endometriosis (EMS) has been observed in emerging research. Alterations in the composition and function of the GM have been described in many studies on EMS. In contrast, the GM in the environment of EMS, especially the GM metabolites, such as bile acids and short-chain fatty acids that are related to the pathogenesis of EMS, can promote disease progression. Chenodeoxycholic acid (CDCA), as one of the primary bile acids produced in the liver, is metabolized by various enzymes derived from the GM and is critically important in maintaining intestinal homeostasis and regulating lipid and carbohydrate metabolism and innate immunity. Given that the complexity of CDCA as a signalling molecule and the interaction between the GM and EMS have not been clarified, the role of the CDCA and GM in EMS should be understood from a novel perspective. However, few articles on the relationship between CDCA and EMS have been reviewed. Therefore, we review the available and possible potential links between CDCA, the GM and EMS and put forward the hypothesis that CDCA and its derivative obeticholic acid can improve the symptoms of EMS through the GM.
Meta-analysis and trial sequential analysis of shexiang baoxin pill for coronary slow flow
Authors: Guo Hongxin , Li Xingyuan , Zhu Mingjun
Published: August 2022

Background: Coronary slow flow (CSF) is a common cardiovascular phenomenon with no effective treatment in conventional Western medicine (CWM). Shexiang Baoxin Pill (SXBXP) is a widely used Chinese medicine for cardiovascular disease in China, and clinical studies have shown that it has good efficacy for CSF.

Objective: To systematically evaluate the efficacy and safety of SXBXP for CSF.

Methods: Seven databases were searched to identify related randomized controlled trials (RCTs). The Meta-analysis, trial sequential analysis (TSA), and Grades of Recommendation, Assessment, Development and Evaluation (GRADE) were performed using Stata 14.1, TSA 0.9.5.10 Beta and GRADE profiler 3.2.2 software respectively.

Results: A total of 10 RCTs were included. Meta-analysis showed that compared with CWM treatment alone, SXBXP combined with CWM further improved the angina pectoris efficacy [RR = 1.37, 95% CI (1.23, 1.52), p < 0.000 01] and nitric oxide (NO) level [WMD = 11.32, 95% CI (0.04, 22.59), p = 0.049], decreased the mean corrected TIMI frame count (CTFC) [WMD = −4.23, 95% CI (−5.51, −2.95), p < 0.000 01], CTFC of the left anterior descending artery (LAD) [WMD = −6.36, 95% CI (−12.07, −0.65), p = 0.029], left circumflex artery (LCX) [WMD = -5.73, 95% CI (−8.79, −2.67), p < 0.000 01], and right coronary artery (RCA) [WMD = −6.72, 95% CI (−10.60, −2.84), p = 0.001], decreased the positive rate of treadmill exercise test [RR = 0.45, 95% CI (0.25, 0.83), p = 0.010], endothelin-1 (ET-1) level [WMD = -11.03, 95% CI (−13.92, −8.14), p < 0.000 01], high-sensitivity C-reactive protein (hs-CRP) [WMD = −1.95, 95% CI (−2.57, −1.34), p < 0.000 01], and adverse reactions [RR = 0.20, 95% CI (0.05, 0.85), p = 0.030]. The GRADE evidence quality rating presented with moderate, low or very low quality of evidence. TSA further affirmed the clinical efficacy.

Conclusion: Although some results suggest that there may be a positive effect of SXBXP for CSF, the quality of the primary study including the reporting is too poor and therefore, no benefits could be demonstrated. More high-quality studies are still needed to further confirm the efficacy and safety.

Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022329469).
Cytochrome P450-mediated antiseizure medication interactions influence apoptosis, modulate the brain BAX/Bcl-XL ratio and aggravate mitochondrial stressors in human pharmacoresistant epilepsy
Authors: Ghosh Chaitali , Westcott Rosemary , Perucca Emilio , Hossain Mohammed , Bingaman William , Najm Imad
Published: August 2022

Polytherapy with antiseizure medications (ASMs) is often used to control seizures in patients suffering from epilepsy, where about 30% of patients are pharmacoresistant. While drug combinations are intended to be beneficial, the consequence of CYP-dependent drug interactions on apoptotic protein levels and mitochondrial function in the epileptic brain remains unclear. We examined the interactions of ASMs given prior to surgery in surgically resected brain tissues and of three ASMs (lacosamide, LCM; oxcarbazepine, OXC; levetiracetam LEV) in isolated brain cells from patients with drug-resistant epilepsy (n = 23). We divided the patients into groups–those who took combinations of NON-CYP + CYP substrate ASMs, NON-CYP + CYP inducer ASMs, CYP substrate + CYP substrate or CYP substrate + CYP inducer ASMs–to study the 1) pro- and anti-apoptotic protein levels and other apoptotic signaling proteins and levels of reactive oxygen species (reduced glutathione and lipid peroxidation) in brain tissues; 2) cytotoxicity at blood-brain barrier epileptic endothelial cells (EPI-ECs) and subsequent changes in mitochondrial membrane potential in normal neuronal cells, following treatment with LCM + OXC (CYP substrate + CYP inducer) or LCM + LEV (CYP substrate + NON-CYP-substrate) after blood-brain barrier penetration, and 3) apoptotic and mitochondrial protein targets in the cells, pre-and post-CYP3A4 inhibition by ketoconazole and drug treatments. We found an increased BAX (pro-apoptotic)/Bcl-XL (anti-apoptotic) protein ratio in epileptic brain tissue after treatment with CYP substrate + CYP substrate or inducer compared to NON-CYP + CYP substrate or inducer, and subsequently decreased glutathione and elevated lipid peroxidation levels. Further, increased cytotoxicity and Mito-ID levels, indicative of compromised mitochondrial membrane potential, were observed after treatment of LCM + OXC in combination compared to LCM + LEV or these ASMs alone in EPI-ECs, which was attenuated by pre-treatment of CYP inhibitor, ketoconazole. A combination of two CYP-mediated ASMs on EPI-ECs resulted in elevated caspase-3 and cytochrome c with decreased SIRT3 levels and activity, which was rescued by CYP inhibition. Together, the study highlights for the first time that pro- and anti-apoptotic proteins levels are dependent on ASM combinations in epilepsy, modulated via a CYP-mediated mechanism that controls free radicals, cytotoxicity and mitochondrial activity. These findings lead to a better understanding of future drug selection choices offsetting pharmacodynamic CYP-mediated interactions.
Determination of Static and Dynamic Yield Stress of Chengdu Clay Slurry
Authors: XianJun Ji , Ying Liang , WenHao Cao , XiaoKang Sun , Peng Song
Published: August 2022

The yield stress of mud is one key to analyze the initiation and deposition of debris flow. Taking Chengdu clay as the experimental material, slurries with different solid volume concentrations were prepared. Using the blade rotor system of mcr301 rheometer and the continuous shear experimental method, the dynamic change process of shear stress of slurries with different solid volume concentrations was obtained with the shear rate increasing and decreasing continuously. According to the experimental results, the static and dynamic yield stress of Chengdu clay slurry is determined, and the influence of solid volume concentration on the yield stress is analyzed. The following conclusions are obtained: Chengdu clay slurry is a non-Newtonian fluid with yield stress. In the process of accelerated shear, for Chengdu clay slurry with solid volume concentration exceeding 35%, the shear rate is in the range of 0.01–1 s−1, and the shear stress increases rapidly to the maximum. When the shear rate exceeds 1 s−1, the shear stress decreases rapidly and finally tends to be stable. The shear rate appears stress overshoot near 1s−1. However, in the process of increasing shear rate, for Chengdu clay slurry with solid volume concentration of no more than 35%, the shear stress increases rapidly in the range of shear rate of 0.01–0.1 s−1, and the shear rate exceeds 0.1 s−1. The shear rate has little effect on the shear stress, and the stress overshoot disappears. In the process of deceleration shear, for all solid volume concentrations in the semi logarithmic coordinate system, the mud shear stress decreases steadily with the decrease of shear rate. The static and dynamic yield stress of slurry increases exponentially with particle concentration.
Label-free observation of morphological alteration of irradiated-urothelial bladder carcinoma cells through digital holographic microscopy
Authors: Xiao Xi , Che Leiping , Li Yinjia , Peng Ran , Wang Mingqing , Xiao Wen , Pan Feng , Wang Hao
Published: August 2022

Radiotherapy is an effective treatment for certain patients with muscle-invasive bladder cancer and radio-sensitivity detection plays a vital role during bladder cancer radio treatment because radiotherapy responses have profound influences on a patient’s prognosis. Although several potential biomarkers were investigated to assess the radio-response of bladder cancer, studies on detecting radio-sensitivity based on morphological characteristics of cancer cells at the single-cell level are rare. In fact, morphological parameters are vital characteristics of cells that could provide direct information to infer the physiological statuses of cells and evaluate the response of cells to the external stimulations. In this study, digital holographic microscopy was applied to quantify morphological parameters of bladder cancer cells (HT-1376) at the single-cell level and their alterations after exposure to four different radiation doses, i.e., 0 Gy (control), 4, 8, and 12 Gy. Based on the reconstructed phase images, four morphological parameters of cells, namely, cell phase volume (CPV), cell projected area (CPA), cell average phase height (CAPH), and cell maximum phase height (CMPH), were quantitatively calculated. The results show that the change rates of CPV, CAPH, and CMPH were increased with the radiation dose rising, while the change rate of CPA was decreased with the radiation dose increasing. Moreover, the change rates of CPV, CPA, CAPH, and CMPH were different between control group and 12 Gy treated group. The results demonstrate that morphological characteristics have the potential to be utilized to estimate the radio-sensitivity of bladder cancer cells, and it may provide new perspectives to establishing label-free methods to detect radio-sensitivity and guide radiotherapy in bladder cancer.
Enhancement of permittivity off-diagonal terms in rare earth transition metal / heavy metal hetero-structured films
Authors: Matsumoto Kei , Thach Pham Van , Sumi Satoshi , Ranjbar Sina , Tanabe Kenji , Awano Hiroyuki , Wang Shihao , Ishibashi Takayuki , Saito Shin
Published: August 2022

The spin Hall effect, Dzyaloshinskii-Moriya interaction, Rashba effect, etc. are extremely important effects for the development of the conduction phenomenon of spin electronics due to the breaking of the spatial inversion symmetry of the hetero interface made of heavy metals such as Pt and W. These are due to SOI (spin-orbit interaction). Most of these studies have been conducted in the frequency domain below GHz, and there are few studies in the energy domain of light. Therefore, in the region of light energy, the magnetic optical Kerr effect spectra of the TbCo/Pt hetero-structured film with large SOI from the Pt interface and the TbCo/Cu hetero-structured film with small SOI from the Cu interface were measured, and the permittivity tensors were investigated respectively. As a result, in the TbCo/Pt hetero-structured film, the dielectric constant off-diagonal component real part of the thin TbCo layer increased about twice as much as that of bulk TbCo in the energy region smaller than 2.5 eV. However, this increase was not observed in the TbCo/Cu hetero-structured film. This result suggests that the influence of the Pt hetero interface where the spatial inversion symmetry is broken may appear even in the energy region of light. Furthermore, it has been confirmed that TbCo/W hetero-structured film using W with a large SOI has the same increasing effect as that of the TbCo/Pt.
Application of a multicomponent model of convectional reaction-diffusion to description of glucose gradients in a neurovascular unit
Authors: Nartsissov Yaroslav R.
Published: August 2022

A supply of glucose to a nervous tissue is fulfilled by a cerebrovascular network, and further diffusion is known to occur at both an arteriolar and a microvascular level. Despite a direct relation, a blood flow dynamic and reaction-diffusion of metabolites are usually considered separately in the mathematical models. In the present study they are coupled in a multiphysical approach which allows to evaluate the effects of capillary blood flow changes on near-vessels nutrient concentration gradients evidently. Cerebral blood flow (CBF) was described by the non-steady-state Navier-Stokes equations for a non-Newtonian fluid whose constitutive law is given by the Carreau model. A three-level organization of blood–brain barrier (BBB) is modelled by the flux dysconnectivity functions including densities and kinetic properties of glucose transporters. The velocity of a fluid flow in brain extracellular space (ECS) was estimated using Darcy’s law. The equations of reaction-diffusion with convection based on a generated flow field for continues and porous media were used to describe spatial-time gradients of glucose in the capillary lumen and brain parenchyma of a neurovascular unit (NVU), respectively. Changes in CBF were directly simulated using smoothing step-like functions altering the difference of intracapillary pressure in time. The changes of CBF cover both the decrease (on 70%) and the increase (on 50%) in a capillary flow velocity. Analyzing the dynamics of glucose gradients, it was shown that a rapid decrease of a capillary blood flow yields an enhanced level of glucose in a near-capillary nervous tissue if the contacts between astrocytes end-feet are not tight. Under the increased CBF velocities the amplitude of glucose concentration gradients is always enhanced. The introduced approach can be used for estimation of blood flow changes influence not only on glucose but also on other nutrients concentration gradients and for the modelling of distributions of their concentrations near blood vessels in other tissues as well.
Dietary ferulic acid supplementation improved cottonseed meal-based diet utilization by enhancing intestinal physical barrier function and liver antioxidant capacity in grass carp (Ctenopharyngodon Idellus)
Authors: Chen Shiyou , Lin Yan , Shi Hequn , Miao Linghong , Liu Bo , Ge Xianping
Published: August 2022

The present study explored the effects of ferulic acid (FA) supplementation in cottonseed meal (CSM)-based diets on grass carp growth performance, feed utilization, liver antioxidation status, and intestinal physical barrier function. Here, four experimental diets supplemented with FA at graded levels (0, 50, 100 and 200 mg/kg) and CSM as the main protein source (384.6 g/kg feed) for an 8-week feeding trial. Our results indicated that 200 mg/kg FA supplementation in a CSM-based diet significantly improved growth performance [including final body weight (FBW), weight gain rate, and specific growth rate] and feed utilization [including feed conversion ratio and protein efficiency ratio] in grass carp (p < 0.05). The results of polynomial regression analysis based on FBW recommended that the optimal dose for FA supplementation was 204 mg/kg. Compared with that no FA supplementation, 200 mg/kg FA supplementation significantly reduced liver malondialdehyde levels and increased glutathione reductase activities (p < 0.05) and 100 mg/kg FA supplementation significantly increased liver total superoxide dismutase activities and reduced blood alanine transaminase levels (p < 0.05). Compared with the control group, 100 mg/kg FA supplementation also led to significantly increased mRNA expression of zo-1, zo-2, occludin, claudin-b, claudin-3, claudin-7a, and claudin-12, encoding intestinal tight junction proteins (p < 0.05). Notably, FA supplementation could reduce lipid deposition by regulating bile acid (BA) secretion. In this study, 100 and 200 mg/kg FA supplementation significantly increased blood and liver total BA levels, respectively (p < 0.05); 100 mg/kg FA also significantly activated mRNA expressions of fxr and cyp7a1 (p < 0.05). Furthermore, the whole-body composition results presented that FA treatment relieved lipid deposition, particularly 50 and 200 mg/kg FA supplementation (p < 0.05). Moreover, triglyceride and total cholesterol levels were significantly lower and high-density lipoprotein levels were significantly higher with 200 mg/kg FA supplementation than with no FA supplementation (p < 0.05). Taken together, the results indicated that FA may be a beneficial feed additive to boost fish growth performance and increase CSM utilization.
Insights Into Chemosensory Proteins From Non-Model Insects: Advances and Perspectives in the Context of Pest Management
Authors: Lizana Paula , Mutis Ana , Quiroz Andrés , Venthur Herbert
Published: August 2022

Nowadays, insect chemosensation represents a key aspect of integrated pest management in the Anthropocene epoch. Olfaction-related proteins have been the focus of studies due to their function in vital processes, such ashost finding and reproduction behavior. Hence, most research has been based on the study of model insects, namely Drosophila melanogaster, Bombyx mori or Tribolium castaneum. Over the passage of time and the advance of new molecular techniques, insects considered non-models have been studied, contributing greatly to the knowledge of insect olfactory systems and enhanced pest control methods. In this review, a reference point for non-model insects is proposed and the concept of model and non-model insects is discussed. Likewise, it summarizes and discusses the progress and contribution in the olfaction field of both model and non-model insects considered pests in agriculture.
Clinical utility of the pancreatitis activity scoring system in severe acute pancreatitis
Authors: Yu Zetao , Ni Qingqiang , Zhang Peng , Jia Hongtao , Yang Faji , Gao Hengjun , Zhu Huaqiang , Liu Fangfeng , Zhou Xu , Chang Hong , Lu Jun
Published: August 2022

Objective: To analyze clinical utility of pancreatitis activity scoring system (PASS) in prediction of persistent organ failure, poor prognosis, and in-hospital mortality in patients with moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) admitted to the intensive care unit (ICU).

Methods: The study included a total of 140 patients with MSAP and SAP admitted to the ICU of Shandong Provincial Hospital from 2015 to 2021. The general information, biochemical indexes and PASS scores of patients at ICU admission time were collected. Independent risk factors of persistent organ failure, poor prognosis and in-hospital mortality were analyzed by binary logistic regression. Through receiver operating characteristic curve (ROC), the predictive ability of lactic acid, procalcitonin, urea nitrogen, PASS, and PASS in combination with urea nitrogen for the three outcomes was compared. The best cut-off value was determined.

Results: Binary logistic regression showed that PASS might be an independent risk factor for patients with persistent organ failure (odds ratio [OR]: 1.027, 95% confidence interval [CI]: 1.014–1.039), poor prognosis (OR: 1.008, 95% CI: 1.001–1.014), and in-hospital mortality (OR: 1.009, 95% CI: 1.000–1.019). PASS also had a good predictive ability for persistent organ failure (area under the curve (AUC) = 0.839, 95% CI: 0.769–0.910) and in-hospital mortality (AUC = 0.780, 95% CI: 0.669–0.891), which was significantly superior to lactic acid, procalcitonin, urea nitrogen and Ranson score. PASS (AUC = 0.756, 95% CI: 0.675–0.837) was second only to urea nitrogen (AUC = 0.768, 95% CI: 0.686–0.850) in the prediction of poor prognosis. Furthermore, the predictive power of urea nitrogen in combination with PASS was better than that of each factor for persistent organ failure (AUC = 0.849, 95% CI: 0.779–0.920), poor prognosis (AUC = 0.801, 95% CI: 0.726–0.876), and in-hospital mortality (AUC = 0.796, 95% CI: 0.697–0.894).

Conclusion: PASS was closely correlated with the prognosis of patients with MSAP and SAP. This scoring system may be used as a common clinical index to measure the activity of acute pancreatitis and evaluate disease prognosis.
Between-day reliability of cytokines and adipokines for application in research and practice
Authors: Rose Grace L. , Farley Morgan J. , Flemming Nicole B. , Skinner Tina L. , Schaumberg Mia A.
Published: August 2022

Purpose: This study assessed the biological reliability of peripheral human cytokines and adipokines, and the influence of participant characteristics on total error. This has essential application to interventional cytokine measurement to ensure that reported results are interpreted with confidence.

Methods: Participants (49% female, 18–85 years, n = 84) completed two consecutive-day testing sessions. Participants provided a venous blood sample at the same time of day across two consecutive days, under standardized participant presentation, including 24-h rested and 12-h fasted conditions. Multiplex immunoassay was used to assess inflammatory analytes from samples (predominantly plasma). Repeat measurements were conducted between-day for total precision quantification, and technical (technique) error was negated from the total to provide an estimate of biological (attributed to participant presentation) error.

Results: Whilst there was no evidence of statistically significant biological error, a small amount of biological error was consistently present across most analytes (∼3.3%/0.07 pg/ml), which was largest for measurement of leptin (7.3%/210 pg/ml). There was also an influence of sex on reliability of leptin and adiponectin (total model explained 6–7% of error variation), where females demonstrated the greatest error.

Conclusion: Biological error reported in this study should be applied to any future study or individual with a repeated measurement of cytokine concentrations over time that maintain best practice procedures (12-h fasted, 24-h rested). In most cases, raw error should be used, with exceptions for women for measurement of leptin and adiponectin. This approach will ensure that results are reported with certainty for improved reporting of intervention efficacy.
Ultrasound-based nomogram for postpartum hemorrhage prediction in pernicious placenta previa
Authors: Zhou Yangzi , Song Zixuan , Wang Xiaoxue , Zhang Mingjie , Chen Xueting , Zhang Dandan
Published: August 2022

Background: Pernicious placenta previa (PPP) is one of the most dangerous complications in pregnancy after cesarean section, with high perinatal mortality. This study aimed to develop a nomogram to predict postpartum hemorrhage in patients with PPP.

Methods: A total of 246 patients with confirmed PPP at Shengjing Hospital of China Medical University from January 2018 to December 2021 were included. Patients were divided into to two cohorts depending on a postpartum blood loss of > 1000 ml (n = 146) or ≤ 1000 ml (n = 100). Lasso regression analysis was performed on the risk factors screened by univariate analysis to screen out the final risk factors affecting postpartum hemorrhage. Based on the final risk factors, a Nomogram prediction model with excellent performance was constructed using Logistic regression. A nomogram was constructed with further screening of the selected risk factors of postpartum hemorrhage in PPP. A second nomogram based only on the total ultrasonic risk score was constructed. Decision curve analysis (DCA) was used to evaluate the clinical efficacy of the nomograms.

Results: Older age, larger gestational age, larger neonatal birth weight, presence of gestational diabetes mellitus, larger amniotic fluid index, absence of gestational bleeding, and higher ultrasonic risk single score were selected to establish a nomogram for postpartum hemorrhage in PPP. The area under the curve of the nomogram constructed by Lasso regression analysis was higher than that of the ultrasonic total score alone (0.887 vs. 0.833). Additionally, DCA indicated better clinical efficacy in the former nomogram than in the later nomogram. Furthermore, internal verification of the nomogram constructed by Lasso regression analysis showed good agreement between predicted and actual values.

Conclusion: A nomogram for postpartum hemorrhage in PPP was developed and validated to assist clinicians in evaluating postpartum hemorrhage. This nomogram was more accurate than using the ultrasonic score alone.
Cell types as species: Exploring a metaphor
Authors: Doyle Jeff J.
Published: August 2022

The concept of “cell type,” though fundamental to cell biology, is controversial. Cells have historically been classified into types based on morphology, physiology, or location. More recently, single cell transcriptomic studies have revealed fine-scale differences among cells with similar gross phenotypes. Transcriptomic snapshots of cells at various stages of differentiation, and of cells under different physiological conditions, have shown that in many cases variation is more continuous than discrete, raising questions about the relationship between cell type and cell state. Some researchers have rejected the notion of fixed types altogether. Throughout the history of discussions on cell type, cell biologists have compared the problem of defining cell type with the interminable and often contentious debate over the definition of arguably the most important concept in systematics and evolutionary biology, “species.” In the last decades, systematics, like cell biology, has been transformed by the increasing availability of molecular data, and the fine-grained resolution of genetic relationships have generated new ideas about how that variation should be classified. There are numerous parallels between the two fields that make exploration of the “cell types as species” metaphor timely. These parallels begin with philosophy, with discussion of both cell types and species as being either individuals, groups, or something in between (e.g., homeostatic property clusters). In each field there are various different types of lineages that form trees or networks that can (and in some cases do) provide criteria for grouping. Developing and refining models for evolutionary divergence of species and for cell type differentiation are parallel goals of the two fields. The goal of this essay is to highlight such parallels with the hope of inspiring biologists in both fields to look for new solutions to similar problems outside of their own field.
The paradoxes hidden behind the Droop model highlighted by a metabolic approach
Authors: Baroukh Caroline , Mairet Francis , Bernard Olivier
Published: August 2022

We propose metabolic models for the haptophyte microalgae Tisochrysis lutea with different possible organic carbon excretion mechanisms. These models—based on the DRUM (Dynamic Reduction of Unbalanced Metabolism) methodology—are calibrated with an experiment of nitrogen starvation under day/night cycles, and then validated with nitrogen-limited chemostat culture under continuous light. We show that models including exopolysaccharide excretion offer a better prediction capability. It also gives an alternative mechanistic interpretation to the Droop model for nitrogen limitation, which can be understood as an accumulation of carbon storage during nitrogen stress, rather than the common belief of a nitrogen pool driving growth. Excretion of organic carbon limits its accumulation, which leads to a maximal C/N ratio (corresponding to the minimum Droop N/C quota). Although others phenomena—including metabolic regulations and dissipation of energy—are possibly at stake, excretion appears as a key component in our metabolic model, that we propose to include in the Droop model.
Loss of function of VdDrs2, a P4-ATPase, impairs the toxin secretion and microsclerotia formation, and decreases the pathogenicity of Verticillium dahliae
Authors: Ren Hui , Li Xianbi , Li Yujie , Li Mengjun , Sun Jiyuan , Wang Fanlong , Zeng Jianyan , Chen Yang , Wang Lei , Yan Xingying , Fan Yanhua , Jin Dan , Pei Yan
Published: August 2022

Four P4-ATPase flippase genes, VdDrs2, VdNeo1, VdP4-4, and VdDnf1 were identified in Verticillium dahliae, one of the most devastating phytopathogenic fungi in the world. Knock out of VdDrs2, VdNeo1, and VdP4-4, or knock down of VdDnf1 significantly decreased the pathogenicity of the mutants in cotton. Among the mutants, the greatest decrease in pathogenicity was observed in ΔVdDrs2. VdDrs2 was localized to plasma membrane, vacuoles, and trans-Golgi network (TGN). In vivo observation showed that the infection of the cotton by ΔVdDrs2 was significantly delayed. The amount of two known Verticillium toxins, sulfacetamide, and fumonisin B1 in the fermentation broth produced by the ΔVdDrs2 strain was significantly reduced, and the toxicity of the crude Verticillium wilt toxins to cotton cells was attenuated. In addition, the defect of VdDrs2 impaired the synthesis of melanin and the formation of microsclerotia, and decreased the sporulation of V. dahliae. Our data indicate a key role of P4 ATPases-associated vesicle transport in toxin secretion of disease fungi and support the importance of mycotoxins in the pathogenicity of V. dahliae.
Combined morphological and multi-omics analyses to reveal the developmental mechanism of Zanthoxylum bungeanum prickles
Authors: Su Kexing , Sun Jiaqian , Han Jun , Zheng Tao , Sun Bingyin , Liu Shuming
Published: August 2022

Zanthoxylum bungeanum Maxim. as an important economic forest, its epidermis bears prickles which complicate the harvesting process and increase the labor costs. To explore the developmental mechanism of prickles, three varieties of Zanthoxylum bungeanum (PZB, SZB, GSZB) were selected for morphological and multi-omics analyses. The absorption spectra of prickles and stems were detected using Fourier-transform infrared spectroscopy (FTIR), and they were found different at 1617, 1110, 3319, and 1999 cm–1. The morphology of prickles and stems were observed using light microscopy and transmission electron microscopy (TEM). The growth direction of cells on the prickle side and stem side were perpendicular to each other, and there was a resembling abscission zone (RAZ) between them. The vacuolar deposits of prickle cells were much more than stem cells, indicating that the lignification degree of prickles was higher than stems. In addition, 9 candidate genes (ZbYABBY2, ZbYABBY1, ZbYABBY5, ZbWRKY, ZbLOG5, ZbAZG2, ZbGh16, ZbIAA33, and ZbGh16X1) were screened out and validated base on transcriptome and qRT-PCA. As well as, 30 key metabolites were found related to prickle development base on metabolome analysis. Among them, 4-hydroxy-2-oxopentanoate, trans-2-hydroxy-cinnamate, trans-cinnamate, polyhydroxy-fatty acid, 10,16-dihydroxypalmitate, cinnamic acid were related to the biosynthesis of cutin, suberine and wax. Indole-3-acetate, tryptamine, anthranilate, fromylanthranilate, N6-(delta2-isopentenyl)-adenine were related to plant hormone signal transduction. Generally, this is the first study to reveal the developmental mechanism of prickles. The results of this study lay the foundation for the breeding of non-prickle Zanthoxylum bungeanum.
Regulation and physiological function of proteins for heat tolerance in cowpea (Vigna unguiculata) genotypes under controlled and field conditions
Authors: Selinga Tonny I. , Maseko Sipho T. , Gabier Hawwa , Rafudeen Mohammed S. , Muasya A. Muthama , Crespo Olivier , Ogola John B. O. , Valentine Alex J. , Ottosen Carl-Otto , Rosenqvist Eva , Chimphango Samson B. M.
Published: August 2022

The expression of heat shock proteins is considered a central adaptive mechanism to heat stress. This study investigated the expression of heat shock proteins (HSPs) and other stress-protective proteins against heat stress in cowpea genotypes under field (IT-96D-610 and IT-16) and controlled (IT-96D-610) conditions. Heat stress response analysis of proteins at 72 h in the controlled environment showed 270 differentially regulated proteins identified using label-free quantitative proteomics in IT-96D-610 plants. These plants expressed HSPs and chaperones [BAG family molecular chaperone 6 (BAG6), Multiprotein bridging factor1c (MBF1C) and cold shock domain protein 1 (CSDP1) in the controlled environment]. However, IT-96D-610 plants expressed a wider variety of small HSPs and more HSPs in the field. IT-96D-610 plants also responded to heat stress by exclusively expressing chaperones [DnaJ chaperones, universal stress protein and heat shock binding protein (HSBP)] and non-HSP proteins (Deg1, EGY3, ROS protective proteins, temperature-induced lipocalin and succinic dehydrogenase). Photosynthesis recovery and induction of proteins related to photosynthesis were better in IT-96D-610 because of the concurrent induction of heat stress response proteins for chaperone functions, protein degradation for repair and ROS scavenging proteins and PSII operating efficiency (Fq’/Fm′) than IT-16. This study contributes to identification of thermotolerance mechanisms in cowpea that can be useful in knowledge-based crop improvement.
Nitrogen use efficiency in cotton: Challenges and opportunities against environmental constraints
Authors: Shah Adnan Noor , Javed Talha , Singhal Rajesh Kumar , Shabbir Rubab , Wang Depeng , Hussain Sadam , Anuragi Hirdayesh , Jinger Dinesh , Pandey Himanshu , Abdelsalam Nader R. , Ghareeb Rehab Y. , Jaremko Mariusz
Published: August 2022

Nitrogen is a vital nutrient for agricultural, and a defieciency of it causes stagnate cotton growth and yield penalty. Farmers rely heavily on N over-application to boost cotton output, which can result in decreased lint yield, quality, and N use efficiency (NUE). Therefore, improving NUE in cotton is most crucial for reducing environmental nitrate pollution and increasing farm profitability. Well-defined management practices, such as the type of sources, N-rate, application time, application method, crop growth stages, and genotypes, have a notable impact on NUE. Different N formulations, such as slow and controlled released fertilizers, have been shown to improve N uptake and, NUE. Increasing N rates are said to boost cotton yield, although high rates may potentially impair the yield depending on the soil and environmental conditions. This study comprehensively reviews various factors including agronomic and environmental constraints that influence N uptake, transport, accumulation, and ultimately NUE in cotton. Furthermore, we explore several agronomic and molecular approaches to enhance efficiency for better N uptake and utilization in cotton. Finally, this objective of this review to highlight a comprehensive view on enhancement of NUE in cotton and could be useful for understanding the physiological, biochemical and molecular mechanism of N in cotton.