bluuebunny/crossref_metadata_2025 huggingface dataset:
GM-CSF Programs Hematopoietic Stem and Progenitor Cells During Candida albicans Vaccination for Protection Against Reinfection
Authors: Bono Cristina , Guerrero Paula , Jordán-Pla Antonio , Erades Ana , Salomonis Nathan , Grimes H. Leighton , Gil M. Luisa , Yáñez Alberto
Published: December 2021

More mechanistic studies are needed to reveal the hidden details of in vivo-induced trained immunity. Here, using a Candida albicans live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vaccination expands and reprograms hematopoietic stem and progenitor cells (HSPCs) early during infection and mobilize them transiently to the spleen to produce trained macrophages. Trained HSPCs are not only primed for myeloid cell production but also reprogramed to produce a greater amount of proinflammatory cytokines in response to a second challenge. Additionally, their adoptive transfer is sufficient to protect mice against reinfection. Mechanistically, autocrine GM-CSF activation of HSPCs is responsible for the trained phenotype and essential for the vaccine-induced protection. Our findings reveal a fundamental role for HSPCs in the trained immune protective response, opening new avenues for disease prevention and treatment.
Transcriptome Profiling Reveals Features of Immune Response and Metabolism of Acutely Infected, Dead and Asymptomatic Infection of African Swine Fever Virus in Pigs
Authors: Sun Hualin , Niu Qingli , Yang Jifei , Zhao Yaru , Tian Zhancheng , Fan Jie , Zhang Zhonghui , Wang Yiwang , Geng Shuxian , Zhang Yulong , Guan Guiquan , Williams David T. , Luo Jianxun , Yin Hong , Liu Zhijie
Published: December 2021

African swine fever virus (ASFV) infection can result in lethal disease in pigs. ASFV encodes 150-167 proteins, of which only approximately 50 encoded viral structure proteins are functionally known. ASFV also encodes some nonstructural proteins that are involved in the regulation of viral transcription, viral replication and evasion from host defense. However, the understanding of the molecular correlates of the severity of these infections is still limited. The purpose of this study was to compare host and viral gene expression differences and perform functional analysis in acutely infected, dead and cohabiting asymptomatic pigs infected with ASFV by using RNA-Seq technique; healthy pigs were used as controls. A total of 3,760 and 2,874 upregulated genes and 4,176 and 2,899 downregulated genes were found in healthy pigs vs. acutely infected, dead pigs or asymptomatic pigs, respectively. Additionally, 941 upregulated genes and 956 downregulated genes were identified in asymptomatic vs. acutely infected, dead pigs. Different alternative splicing (AS) events were also analyzed, as were gene chromosome locations, and protein-protein interaction (PPI) network prediction analysis was performed for significantly differentially expressed genes (DEGs). In addition, 30 DEGs were validated by RT-qPCR, and the results were consistent with the RNA-Seq results. We further analyzed the interaction between ASFV and its host at the molecular level and predicted the mechanisms responsible for asymptomatic pigs based on the selected DEGs. Interestingly, we found that some viral genes in cohabiting asymptomatic pigs might integrate into host genes (DP96R, I73R and L83L) or remain in the tissues of cohabiting asymptomatic pigs. In conclusion, the data obtained in the present study provide new evidence for further elucidating ASFV-host interactions and the ASFV infection mechanism and will facilitate the implementation of integrated strategies for controlling ASF spread.
Flooding of Sandy Beaches in a Changing Climate. The Case of the Balearic Islands (NW Mediterranean)
Authors: Agulles Miguel , Jordà Gabriel , Lionello Piero
Published: December 2021

The fate of the beaches around the world has paramount importance as they are one of the main assets for touristic activities and act as a natural barrier for coastal protection in front of marine storms. Climate change could put them at risk as sea levels rise and changes in the wave characteristics may dramatically modify their shape. In this work, a new methodology has been developed to determine the flooding of sandy beaches due to changes in sea level and waves. The methodology allows a cost-effective and yet accurate estimation of the wave runup for a wide range of beach equilibrium profiles and for different seagrass coverage. This, combined with regional projections of sea level and wave evolution, has allowed a quantification of the future total water level and coastline retreat for 869 beaches across the Balearic Islands for the next decades as a function of greenhouse gases emission scenario. The most pessimistic scenario (RCP8.5) at the end of the century yields an averaged percentage of flooded area of 66% under mean conditions which increases up to 86% under extreme conditions. Moreover, 72 of the 869 beaches of the region would permanently disappear while 314 would be completely flooded during storm episodes. Under a moderate scenario of emissions (RCP4.5), 37 beaches would permanently disappear while 254 would disappear only during storm episodes. In both cases, the average permanent loss of beach surface at the end of the century would be larger than 50%, rising over 80% during storm conditions. The results obtained for the Balearic Islands can be extrapolated to the rest of the Mediterranean as the beaches in all the regions have similar characteristics and will be affected by similar changes in sea level and wave climate. These projections indicate that adaptation plans for beach areas should be put in place as soon as possible.
A Simple Diagnosis-Related Groups-Based Reimbursement System Is Cost Ineffective for Elderly Patients With Displaced Femoral Neck Fracture Undergoing Hemiarthroplasty in Beijing
Authors: Peng Hui-ming , Xu Yuan , Ci Pu-wo , Zhang Jia , Zhang Bao-zhong , Weng Xi-sheng
Published: December 2021

Displaced femoral neck fractures (FNF) in the elderly are a major public health concern that necessitates hemiarthroplasty (HA) as the mainstay treatment option. Diagnosis-Related Groups (DRG) are a patient classification system that categorizes patients based on the resources expended on them. The first objective of this study was to evaluate if a simplified DRG-based reimbursement system in Beijing would lower total HA treatment costs for elderly patients with displaced FNF. In addition, we aimed to determine how age, gender, year of admission, length of in-hospital stay, and the Charlson index affected total treatment costs. This retrospective study included 513 patients from the Peking Union Medical College Hospital. The patients were diagnosed with unilateral displaced femoral neck fractures and had HA. Medical information was gathered, including baseline demographic and clinical data, as well as treatment costs. Patients were classified into two groups: those who spent more than the predetermined cut-off cost and those who did not. The cost did not include the use of a bipolar prosthesis. Data from the two groups were compared, and multiple regression analysis models were constructed. The median total cost of treatment was ¥49,626 ($7,316). The majority of the patients (89.7%; 460/513) were categorized as exceeding the cost cut-off. Multiple linear regression analysis revealed that total treatment cost was positively correlated with age (p < 0.01) and the duration of in-hospital stay (p < 0.01) but not with gender (p = 0.160) or the Charlson index (p = 0.548). On implementing the DRG-based reimbursement system, the overall treatment costs increased by ¥21,028 ($3,099) (p < 0.01). The implementation of simplified DRG-prospective payment systems did not result in a significant reduction in total treatment costs for elderly patients with FNF who underwent HA in Beijing. The overall cost of treatment was associated with several factors, including age, length of hospitalization, and year of admission.
Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis
Authors: Jahandideh Arghavan , Ståhle Mia , Virta Jenni , Li Xiang-Guo , Liljenbäck Heidi , Moisio Olli , Knuuti Juhani , Roivainen Anne , Saraste Antti
Published: December 2021

The 68Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([68Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor αvβ3 integrin that is upregulated during angiogenesis and inflammation. We studied whether αvβ3 targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [68Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [68Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUVmean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [68Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing αvβ3 integrin-positive capillary-like structures. A non-specific [68Ga]Ga-DOTA-(RGE)2 tracer showed 76% lower uptake than [68Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that αvβ3 integrin-targeting [68Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.
Species-Level Analysis of the Human Gut Microbiome Shows Antibiotic Resistance Genes Associated With Colorectal Cancer
Authors: Liu Chuanfa , Li Zhiming , Ding Jiahong , Zhen Hefu , Fang Mingyan , Nie Chao
Published: December 2021

Colorectal cancer (CRC) is the second leading cause of cancer deaths and continuously increases new cancer cases globally. Accumulating evidence links risks of CRC to antibiotic use. Long-term use and abuse of antibiotics increase the resistance of the gut microbiota; however, whether CRC is associated with antibiotic resistance in gut microbiota is still unclear. In this study, we performed a de novo assembly to metagenomic sequences in 382 CRC patients and 387 healthy controls to obtain representative species-level genome bins (rSGBs) and plasmids and analyzed the abundance variation of species and antibiotic resistance genes (ARGs). Twenty-five species and 65 ARGs were significantly enriched in the CRC patients, and among these ARGs, 12 were multidrug-resistant genes (MRGs), which mainly included acrB, TolC, marA, H-NS, Escherichia coli acrR mutation, and AcrS. These MRGs could confer resistance to fluoroquinolones, tetracyclines, cephalosporins, and rifamycin antibiotics by antibiotic efflux and inactivation. A classification model was built using the abundance of species and ARGs and achieved areas under the curve of 0.831 and 0.715, respectively. Our investigation has identified the antibiotic resistance types of ARGs and suggested that E. coli is the primary antibiotic resistance reservoir of ARGs in CRC patients, providing valuable evidence for selecting appropriate antibiotics in the CRC treatment.
Activity of Moxifloxacin Against Biofilms Formed by Clinical Isolates of Staphylococcus aureus Differing by Their Resistant or Persister Character to Fluoroquinolones
Authors: Nguyen Tiep K. , Peyrusson Frédéric , Siala Wafi , Pham Nhung H. , Nguyen Hoang A. , Tulkens Paul M. , Van Bambeke Françoise
Published: December 2021

Staphylococcus aureus biofilms are poorly responsive to antibiotics. Underlying reasons include a matrix effect preventing drug access to embedded bacteria, or the presence of dormant bacteria with reduced growth rate. Using 18 clinical isolates previously characterized for their moxifloxacin-resistant and moxifloxacin-persister character in stationary-phase culture, we studied their biofilm production and matrix composition and the anti-biofilm activity of moxifloxacin. Biofilms were grown in microtiter plates and their abundance quantified by crystal violet staining and colony counting; their content in polysaccharides, extracellular DNA and proteins was measured. Moxifloxacin activity was assessed after 24 h of incubation with a broad range of concentrations to establish full concentration-response curves. All clinical isolates produced more biofilm biomass than the reference strain ATCC 25923, the difference being more important for those with high relative persister fractions to moxifloxacin, most of which being also resistant. High biofilm producers expressed icaA to higher levels, enriching the matrix in polysaccharides. Moxifloxacin was less potent against biofilms from clinical isolates than from ATCC 25923, especially against moxifloxacin-resistant isolates with high persister fractions, which was ascribed to a lower concentration of moxifloxacin in these biofilms. Time-kill curves in biofilms revealed the presence of a moxifloxacin-tolerant subpopulation, with low multiplication capacity, whatever the persister character of the isolate. Thus, moxifloxacin activity depends on its local concentration in biofilm, which is reduced in most isolates with high-relative persister fractions due to matrix effects, and insufficient to kill resistant isolates due to their high MIC.
Characterization of Streptococcus salivarius as New Probiotics Derived From Human Breast Milk and Their Potential on Proliferative Inhibition of Liver and Breast Cancer Cells and Antioxidant Activity
Authors: Srikham Kantapich , Daengprok Wichittra , Niamsup Piyanuch , Thirabunyanon Mongkol
Published: December 2021

Breast milk is well known as the abundant source of beneficial bacteria. A new alternative source of human probiotic origin from breast milk is in demand and currently of interest for both the functional food industry and biopharmaceuticals. The aim in this study was to investigate the anticancer and antioxidant efficacies of the new potential probiotics isolated from human breast milk. Three strains of lactic acid bacteria (LAB) have shown their potential probiotic criteria including antimicrobial activity, non-hemolytic property, and survival in acid and bile salt conditions. These strains showed high abilities on cell surface hydrophobicity, auto-aggregation, and co-aggregation. The genera identification by 16S rRNA sequencing and comparison revealed that they were Streptococcus salivarius BP8, S. salivarius BP156, and S. salivarius BP160. The inhibition of liver cancer cells (HepG2) and breast cancer cells (MCF-7) proliferation by these probiotic strains using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was 44.83–59.65 and 29.85–37.16%, respectively. The probiotic action mode was inducted via apoptotic mechanisms since they stimulate the liver and breast cancer cell death through DNA fragmentation and positive morphological changes by acridine orange (AO) and propidium iodide (PI) staining. The antioxidant activity of these probiotics in the form of intact cells, cell free supernatant (CFS), and heat-killed cells was evaluated by a 2,2–diphenyl–1–picrylhydrazyl (DPPH) assay, resulting in the scavenging activity rates of 16.93–25.43, 15.47–28.03, and 13.67–23.0%, respectively. These S. salivarius probiotic strains protected the L929 mouse fibroblasts against oxidative stress with very high survival rates at 94.04–97.77%, which was significantly higher (P < 0.05) than L-ascorbic acid at 75.89–78.67% in the control groups. The results indicated that S. salivarius BP8 and S. salivarius BP160 probiotic strains could be applied as functional foods or new alternative bioprophylactics for treating liver and breast cancers.
Visualizing Cancer Cell Metabolic Dynamics Regulated With Aromatic Amino Acids Using DO-SRS and 2PEF Microscopy
Authors: Bagheri Pegah , Hoang Khang , Fung Anthony A. , Hussain Sahran , Shi Lingyan
Published: December 2021

Oxidative imbalance plays an essential role in the progression of many diseases that include cancer and neurodegenerative diseases. Aromatic amino acids (AAA) such as phenylalanine and tryptophan have the capability of escalating oxidative stress because of their involvement in the production of Reactive Oxygen Species (ROS). Here, we use D2O (heavy water) probed stimulated Raman scattering microscopy (DO-SRS) and two Photon Excitation Fluorescence (2PEF) microscopy as a multimodal imaging approach to visualize metabolic changes in HeLa cells under excess AAA such as phenylalanine or trytophan in culture media. The cellular spatial distribution of de novo lipogenesis, new protein synthesis, NADH, Flavin, unsaturated lipids, and saturated lipids were all imaged and quantified in this experiment. Our studies reveal ∼10% increase in de novo lipogenesis and the ratio of NADH to flavin, and ∼50% increase of the ratio of unsaturated lipids to saturated lipid in cells treated with excess phenylalanine or trytophan. In contrast, these cells exhibited a decrease in the protein synthesis rate by ∼10% under these AAA treatments. The cellular metabolic activities of these biomolecules are indicators of elevated oxidative stress and mitochondrial dysfunction. Furthermore, 3D reconstruction images of lipid droplets were acquired and quantified to observe their spatial distribution around cells’ nuceli under different AAA culture media. We observed a higher number of lipid droplets in excess AAA conditions. Our study showcases that DO-SRS imaging can be used to quantitatively study how excess AAA regulates metabolic activities of cells with subcellular resolution in situ.
The Epidemiology of Neurological Complications in Adults With Sickle Cell Disease: A Retrospective Cohort Study
Authors: Maduakor Chinedu , Alakbarzade Vafa , Sammaraiee Yezen , Vakrinou Angeliki , Corobana Alina , Sikorska Julia , Rhodes Elizabeth , Pereira Anthony C.
Published: December 2021

Introduction: Risk factors for neurological complications in sickle cell disease differ in the adult and pediatric populations. Here, we focused on neurological complications in adults with sickle cell disease.

Methods: Patients were selected using the audit data from the St George's Hospital Red Cell Database. The genotyping, demographics, clinical data, and investigation findings were collected.

Results: A total of 303 patients were enrolled in the study: hemoglobin S homozygosity (HbSS) genotype 56%, hemoglobin S and C coinheritance (HbSC) genotype 35%, and hemoglobin S and β-thalassemia coinheritance (HbSβ) thalassemia genotype 9%; the mean age was 38.8 years (±13.5 SD) with 46% males. The most common neurological complication was cerebrovascular disease (n = 37, 12%) including those with ischemic stroke (10%), cerebral vasculopathy (3%), and intracranial hemorrhage (1%). Ischemic stroke was common among the HbSS genotype compared with other genotypes (8 vs. 1.6%, p = 0.001). Comparing the patients with sickle cell disease who had suffered a stroke to those who had not, there was a higher proportion of intracranial vasculopathy (p = 0.001, in particular, Moyamoya) and cognitive dysfunction (p < 0.0001).

Conclusion: Our cohort supports previous reports that the most common neurological complication in adult sickle cell patients is cerebrovascular disease. Strategies to prevent cerebral vasculopathy and cognitive impairment should be explored.
Altered Functional Connectivity and Sensory Processing in Blepharospasm and Hemifacial Spasm: Coexistence and Difference
Authors: Fang Ting-Chun , Chen Chun-Ming , Chang Ming-Hong , Wu Chen-Hao , Guo Yi-Jen
Published: December 2021

Background: Blepharospasm (BSP) and hemifacial spasm (HFS) are both facial hyperkinesia however BSP is thought to be caused by maladaptation in multiple brain regions in contrast to the peripherally induced cause in HFS. Plausible coexisting pathophysiologies between these two distinct diseases have been proposed.

Objectives: In this study, we compared brain resting state functional connectivity (rsFC) and quantitative thermal test (QTT) results between patients with BSP, HFS and heathy controls (HCs).

Methods: This study enrolled 12 patients with BSP, 11 patients with HFS, and 15 HCs. All subjects received serial neuropsychiatric evaluations, questionnaires determining disease severity and functional impairment, QTT, and resting state functional MRI. Image data were acquired using seed-based analyses using the CONN toolbox.

Results: A higher cold detection threshold was found in the BSP and HFS patients compared to the HCs. The BSP and HFS patients had higher rsFC between the anterior cerebellum network and left occipital regions compared to the HCs. In all subjects, impaired cold detection threshold in the QTT of lower extremities had a correlation with higher rsFC between the anterior cerebellar network and left lingual gyrus. Compared to the HCs, increased rsFC in right postcentral gyrus in the BSP patients and decreased rsFC in the right amygdala and frontal orbital cortex in the HFS subjects were revealed when the anterior cerebellar network was used as seed.

Conclusions: Dysfunction of sensory processing detected by the QTT is found in the BSP and HSP patients. Altered functional connectivity between the anterior cerebellar network and left occipital region, especially the Brodmann area 19, may indicate the possibility of shared pathophysiology among BSP, HFS, and impaired cold detection threshold. Further large-scale longitudinal study is needed for testing this theory in the future.
Shared and Unshared Feature Extraction in Major Depression During Music Listening Using Constrained Tensor Factorization
Authors: Wang Xiulin , Liu Wenya , Wang Xiaoyu , Mu Zhen , Xu Jing , Chang Yi , Zhang Qing , Wu Jianlin , Cong Fengyu
Published: December 2021

Ongoing electroencephalography (EEG) signals are recorded as a mixture of stimulus-elicited EEG, spontaneous EEG and noises, which poses a huge challenge to current data analyzing techniques, especially when different groups of participants are expected to have common or highly correlated brain activities and some individual dynamics. In this study, we proposed a data-driven shared and unshared feature extraction framework based on nonnegative and coupled tensor factorization, which aims to conduct group-level analysis for the EEG signals from major depression disorder (MDD) patients and healthy controls (HC) when freely listening to music. Constrained tensor factorization not only preserves the multilinear structure of the data, but also considers the common and individual components between the data. The proposed framework, combined with music information retrieval, correlation analysis, and hierarchical clustering, facilitated the simultaneous extraction of shared and unshared spatio-temporal-spectral feature patterns between/in MDD and HC groups. Finally, we obtained two shared feature patterns between MDD and HC groups, and obtained totally three individual feature patterns from HC and MDD groups. The results showed that the MDD and HC groups triggered similar brain dynamics when listening to music, but at the same time, MDD patients also brought some changes in brain oscillatory network characteristics along with music perception. These changes may provide some basis for the clinical diagnosis and the treatment of MDD patients.
Association Cystatin C and Risk of Stroke in Elderly Patients With Obstructive Sleep Apnea: A Prospective Cohort Study
Authors: Su Xiaofeng , Gao Yinghui , Xu Weihao , Li JianHua , Chen Kaibing , Gao Yan , Guo JingJing , Zhao LiBo , Wang Huanhuan , Qian Xiaoshun , Lin Junling , Han Jiming , Liu Lin
Published: December 2021

Background: Few prospective cohort studies have assessed the relationship between Cystatin C (Cys-C) and risk of stroke in elderly patients with obstructive sleep apnea (OSA). The study sought to examine the association between baseline serum Cys-C and long-term risk of stroke among elderly OSA patients.

Methods: A total of 932 patients with OSA, no history of stroke, ≥60 years of age, and complete serum Cys-C records were included in this study. All patients had completed polysomnography (PSG). OSA was defined as an apnea-hypopnea index (AHI) of ≥5 events per hour. Participants were categorized into four groups according to baseline serum Cys-C concentration, split into quartiles. Multivariate Cox regression were used to evaluate the association between Cys-C and the incidence of new-onset stroke.

Results: Stroke occurred in 61 patients during the median 42-month follow-up period. The cumulative incidence rate of stroke was 6.5%, which included 54 patients with ischemic stroke and 7 patients with hemorrhagic stroke. The cumulative incidence of stroke was higher among patients with baseline serum Cys-C concentration of ≥1.15 mg/L when compared with other groups (PLog–rank < 0.001). After adjusting for potential confounding factors in the Cox regression model, patients with a serum Cys-C concentration of ≥1.15 mg/L had a 2.16-fold higher risk of developing stroke compared with patients with serum Cys-C ≤ 0.81 mg/L (HR, 2.16, 95%CI, 1.09–6.60; P = 0.017). Additionally, there was a higher risk in those of age ≥70 years (HR, 3.23, 95%CI, 1.05–9.24; P = 0.010). The receiver-operating characteristic curves showed that the capability of Cys-C to identify elderly patients with OSA who had a long-time risk of stroke was moderate (AUC = 0.731, 95% CI: 0.683–0.779, P = 0.001).

Conclusion: Increased Cys-C concentration was identified as a risk factor in the incidence of stroke in elderly patients with OSA, independent of gender, BMI, hypertension and other risk factors. Additionally, it conferred a higher risk in patients of age ≥70 years.
Case Report: Severe Edema and Marked Weight Gain Induced by Marginal Thiamine Deficiency in a Patient With Alcohol Dependency and Type 2 Diabetes Mellitus
Authors: Tanaka Hitomi , Anno Takatoshi , Takenouchi Haruka , Iwamoto Hideyuki , Kaneto Hideaki , Okimoto Niro , Tomoda Koichi
Published: December 2021

Background: Patients with alcohol use disorder (AUD) may develop peripheral edema due to alcohol-related liver, renal, or heart disease. Thiamine deficiency is reported to occur in AUD and type 2 diabetes mellitus (T2DM). Thiamine deficiency may also cause peripheral edema. Thiamine is essential for optimal glucose metabolism through its role as an essential co-factor for key enzymes in intermediary metabolism. Since glucose metabolism worsens under diabetic conditions, it seems that a relative shortage of thiamine may occur more easily in patients with diabetes mellitus.

Case Presentation: A 59-year-old Japanese man was admitted to the hospital with severe peripheral edema. His background history included alcohol liver disease (ALD), chronic renal failure (CRF), and T2DM. His body mass index (BMI) at admission was 37.7 kg/m2 and this represented a 30 kg increase in body weight over 2 months. Laboratory investigations showed anemia, liver and renal injury, hyperglycemia, and marginal hypothyroidism. The plasma thiamine diphosphate concentration was 20 ng/mL (reference range: 24–66 ng/mL). Diet therapy of 1,600 kcal/day and intravenous fursultiamine hydrochloride therapy (50 mg/once a day, seven days) was commenced in combination with intravenous diuretics. After one week, the plasma thiamine concentration was 853 ng/mL, and the patient's body weight had reduced by 18 kg.

Conclusions: Patients with T2DM and AUD may develop severe peripheral edema in the context of marginal thiamine deficiency. Fursultiamine hydrochloride (50 mg/once a day, seven days) restored normal plasma thiamine concentrations and may have contributed to the rapid resolution of severe peripheral edema in this case. Empirical treatment with thiamine should be considered in patients with severe peripheral edema in the context of AUD and T2DM.
A Traditional Chinese Medicine Plant Extract Prevents Alcohol-Induced Osteopenia
Authors: Qian Dongyang , Zhou Hui , Fan Pan , Yu Tao , Patel Anish , O’Brien Morgan , Wang Zhe , Lu Shiguang , Tong Guoqiang , Shan Yimin , Wang Lei , Gao Yuan , Xiong Yuan , Zhang Lily , Wang Xin , Liu Yuancai , Zhou Shuanhu
Published: December 2021

Traditional Chinese medicine (TCM) has been practiced in the treatment of bone diseases and alcoholism. Chronic excessive alcohol use results in alcohol-induced bone diseases, including osteopenia and osteoporosis, which increases fracture risk, deficient bone repair, and osteonecrosis. This preclinical study investigated the therapeutic effects of TCM herbal extracts in animal models of chronic excessive alcohol consumption-induced osteopenia. TCM herbal extracts (Jing extracts) were prepared from nine Chinese herbal medicines, a combinative herbal formula for antifatigue and immune regulation, including Astragalus, Cistanche deserticola, Dioscorea polystachya, Lycium barbarum, Epimedium, Cinnamomum cassia, Syzygium aromaticum, Angelica sinensis, and Curculigo orchioides. In this study, Balb/c male mice were orally administrated alcohol (3.2 g/kg/day) with/without TCM herbal extracts (0.125 g/kg, 0.25 g/kg, or 0.5 g/kg) by gavage. Our results showed that after 50 days of oral administration, TCM herbal extracts prevented alcohol-induced osteopenia demonstrated by μ-CT bone morphological analysis in young adults and middle-aged/old Balb/c male mice. Biochemical analysis demonstrated that chronic alcohol consumption inhibits bone formation and has a neutral impact on bone resorption, suggesting that TCM herbal extracts (Jing extracts) mitigate the alcohol-induced abnormal bone metabolism in middle-aged/old male mice. Protocatechuic acid, a natural phenolic acid in Jing extracts, mitigates in vivo alcohol-induced decline of alkaline phosphatase (ALP) gene expression in the bone marrow of Balb/c male mice and in vitro ALP activity in pre-osteoblast MC3T3-E1 cells. Our study suggests that TCM herbal extracts prevent chronic excessive alcohol consumption-induced osteopenia in male mice, implying that traditional medicinal plants have the therapeutic potential of preventing alcohol-induced bone diseases.
Yi-Zhi-Fang-Dai Formula Exerts Neuroprotective Effects Against Pyroptosis and Blood–Brain Barrier–Glymphatic Dysfunctions to Prevent Amyloid-Beta Acute Accumulation After Cerebral Ischemia and Reperfusion in Rats
Authors: Lyu Zhongkuan , Li Qiyue , Yu Zhonghai , Chan Yuanjin , Fu Lei , Li Yaming , Zhang Chunyan
Published: December 2021

Background: The dysfunctional blood–brain barrier (BBB)–glymphatic system is responsible for triggering intracerebral amyloid-beta peptide (Aβ) accumulation and acts as the key link between ischemic stroke and dementia dominated by Alzheimer’s disease (AD). Recently, pyroptosis in cerebral ischemia and reperfusion (I/R) injury is demonstrated as a considerable mechanism causing BBB–glymphatic dysfunctions and Aβ acute accumulation in the brain. Targeting glial pyroptosis to protect BBB–glymphatic functions after cerebral I/R could offer a new viewpoint to prevent Aβ accumulation and poststroke dementia. Yi-Zhi-Fang-Dai formula (YZFDF) is an herbal prescription used to cure dementia with multiple effects of regulating inflammatory responses and protecting the BBB against toxic Aβ-induced damage. Hence, YZFDF potentially possesses neuroprotective effects against cerebral I/R injury and the early pathology of poststroke dementia, which evokes our current study.

Objectives: The present study was designed to confirm the potential efficacy of YZFDF against cerebral I/R injury and explore the possible mechanism associated with alleviating Aβ acute accumulation.

Methods: The models of cerebral I/R injury in rats were built by the method of middle cerebral artery occlusion/reperfusion (MCAO/R). First, neurological function assessment and cerebral infarct measurement were used for confirming the efficacy of YZFDF on cerebral I/R injury, and the optimal dosage (YZFDF-H) was selected to conduct the experiments, which included Western blotting detections of pyroptosis, Aβ1-42 oligomers, and NeuN, immunofluorescence observations of glial pyroptosis, aquaporin-4 (AQP-4), and Aβ locations, brain water content measurement, SMI 71 (a specific marker for BBB)/AQP-4 immunohistochemistry, and Nissl staining to further evaluate BBB–glymphatic functions and neuronal damage.

Results: YZFDF obviously alleviated neurological deficits and cerebral infarct after cerebral I/R in rats. Furthermore, YZFDF could inactivate pyroptosis signaling via inhibiting caspase-1/11 activation and gasdermin D cleavage, ameliorate glial pyroptosis and neuroinflammation, protect against BBB collapse and AQP-4 depolarization, prevent Aβ acute accumulation and Aβ1-42 oligomers formation, and reduce neuronal damage and increase neurons survival after reperfusion.

Conclusion: Our study indicated that YZFDF could exert neuroprotective effects on cerebral I/R injury and prevent Aβ acute accumulation in the brain after cerebral I/R associated with inhibiting neuroinflammation-related pyroptosis and BBB–glymphatic dysfunctions.
Therapeutic Mechanism and Key Alkaloids of Uncaria rhynchophylla in Alzheimer’s Disease From the Perspective of Pathophysiological Processes
Authors: Zeng Peng , Su Hong-Fei , Ye Chao-Yuan , Qiu Shuo-Wen , Tian Qing
Published: December 2021

Presently, there is a lack of effective disease-modifying drugs for the treatment of Alzheimer’s disease (AD). Uncaria rhynchophylla (UR) and its predominant active phytochemicals alkaloids have been studied to treat AD. This study used a novel network pharmacology strategy to identify UR alkaloids against AD from the perspective of AD pathophysiological processes and identified the key alkaloids for specific pathological process. The analysis identified 10 alkaloids from UR based on high-performance liquid chromatography (HPLC) that corresponded to 127 targets correlated with amyloid-β (Aβ) pathology, tau pathology and Alzheimer disease pathway. Based on the number of targets correlated with AD pathophysiological processes, angustoline, angustidine, corynoxine and isocorynoxeine are highly likely to become key phytochemicals in AD treatment. Among the 127 targets, JUN, STAT3, MAPK3, CCND1, MMP2, MAPK8, GSK3B, JAK3, LCK, CCR5, CDK5 and GRIN2B were identified as core targets. Based on the pathological process of AD, angustoline, angustidine and isocorynoxeine were identified as the key UR alkaloids regulating Aβ production and corynoxine, isocorynoxeine, dihydrocorynatheine, isorhynchophylline and hirsutine were identified as key alkaloids that regulate tau phosphorylation. The findings of this study contribute to a more comprehensive understanding of the key alkaloids and mechanisms of UR in the treatment of AD, as well as provide candidate compounds for drug research and development for specific AD pathological processes.
Development and Validation of Kompetitive Allele-Specific PCR Assays for Erucic Acid Content in Indian Mustard [Brassica juncea (L.) Czern and Coss.]
Authors: Gill Karanjot Singh , Kaur Gurpreet , Kaur Gurdeep , Kaur Jasmeet , Kaur Sra Simarjeet , Kaur Kawalpreet , Gurpreet Kaur , Sharma Meha , Bansal Mitaly , Chhuneja Parveen , Banga Surinder S.
Published: December 2021

Brassica juncea L. is the most widely cultivated oilseed crop in Indian subcontinent. Its seeds contain oil with very high concentration of erucic acid (≈50%). Of late, there is increasing emphasis on the development of low erucic acid varieties because of reported association of the consumption of high erucic acid oil with cardiac lipidosis. Erucic acid is synthesized from oleic acid by an elongation process involving two cycles of four sequential steps. Of which, the first step is catalyzed by β-ketoacyl-CoA synthase (KCS) encoded by the fatty acid elongase 1 (FAE1) gene in Brassica. Mutations in the coding region of the FAE1 lead to the loss of KCS activity and consequently a drastic reduction of erucic acid in the seeds. Molecular markers have been developed on the basis of variation available in the coding or promoter region(s) of the FAE1. However, majority of these markers are not breeder friendly and are rarely used in the breeding programs. Present studies were planned to develop robust kompetitive allele-specific PCR (KASPar) assays with high throughput and economics of scale. We first cloned and sequenced FAE1.1 and FAE1.2 from high and low erucic acid (<2%) genotypes of B. juncea (AABB) and its progenitor species, B. rapa (AA) and B. nigra (BB). Sequence comparisons of FAE1.1 and FAE1.2 genes for low and high erucic acid genotypes revealed single nucleotide polymorphisms (SNPs) at 8 and 3 positions. Of these, three SNPs for FAE1.1 and one SNPs for FAE1.2 produced missense mutations, leading to amino acid modifications and inactivation of KCS enzyme. We used SNPs at positions 735 and 1,476 for genes FAE1.1 and FAE1.2, respectively, to develop KASPar assays. These markers were validated on a collection of diverse genotypes and a segregating backcross progeny. KASPar assays developed in this study will be useful for marker-assisted breeding, as these can track recessive alleles in their heterozygous state with high reproducibility.
Root Transcriptome and Metabolome Profiling Reveal Key Phytohormone-Related Genes and Pathways Involved Clubroot Resistance in Brassica rapa L.
Authors: Wei Xiaochun , Zhang Yingying , Zhao Yanyan , Xie Zhengqing , Hossain Mohammad Rashed , Yang Shuangjuan , Shi Gongyao , Lv Yanyan , Wang Zhiyong , Tian Baoming , Su Henan , Wei Fang , Zhang Xiaowei , Yuan Yuxiang
Published: December 2021

Plasmodiophora brassicae, an obligate biotrophic pathogen-causing clubroot disease, can seriously affect Brassica crops worldwide, especially Chinese cabbage. Understanding the transcriptome and metabolome profiling changes during the infection of P. brassicae will provide key insights in understanding the defense mechanism in Brassica crops. In this study, we estimated the phytohormones using targeted metabolome assays and transcriptomic changes using RNA sequencing (RNA-seq) in the roots of resistant (BrT24) and susceptible (Y510-9) plants at 0, 3, 9, and 20 days after inoculation (DAI) with P. brassicae. Differentially expressed genes (DEGs) in resistant vs. susceptible lines across different time points were identified. The weighted gene co-expression network analysis of the DEGs revealed six pathways including “Plant–pathogen interaction” and “Plant hormone signal transduction” and 15 hub genes including pathogenic type III effector avirulence factor gene (RIN4) and auxin-responsive protein (IAA16) to be involved in plants immune response. Inhibition of Indoleacetic acid, cytokinin, jasmonate acid, and salicylic acid contents and changes in related gene expression in R-line may play important roles in regulation of clubroot resistance (CR). Based on the combined metabolome profiling and hormone-related transcriptomic responses, we propose a general model of hormone-mediated defense mechanism. This study definitely enhances our current understanding and paves the way for improving CR in Brassica rapa.
Profiling of H3K4me3 and H3K27me3 and Their Roles in Gene Subfunctionalization in Allotetraploid Cotton
Authors: Zhang Aicen , Wei Yangyang , Shi Yining , Deng Xiaojuan , Gao Jingjing , Feng Yilong , Zheng Dongyang , Cheng Xuejiao , Li Zhaoguo , Wang Tao , Wang Kunbo , Liu Fang , Peng Renhai , Zhang Wenli
Published: December 2021

Cotton is an excellent model for studying crop polyploidization and domestication. Chromatin profiling helps to reveal how histone modifications are involved in controlling differential gene expression between A and D subgenomes in allotetraploid cotton. However, the detailed profiling and functional characterization of broad H3K4me3 and H3K27me3 are still understudied in cotton. In this study, we conducted H3K4me3- and H3K27me3-related ChIP-seq followed by comprehensively characterizing their roles in regulating gene transcription in cotton. We found that H3K4me3 and H3K27me3 exhibited active and repressive roles in regulating the expression of genes between A and D subgenomes, respectively. More importantly, H3K4me3 exhibited enrichment level-, position-, and distance-related impacts on expression levels of related genes. Distinct GO term enrichment occurred between A/D-specific and homeologous genes with broad H3K4me3 enrichment in promoters and gene bodies, suggesting that broad H3K4me3-marked genes might have some unique biological functions between A and D subgenome. An anticorrelation between H3K27me3 enrichment and expression levels of homeologous genes was more pronounced in the A subgenome relative to the D subgenome, reflecting distinct enrichment of H3K27me3 in homeologous genes between A and D subgenome. In addition, H3K4me3 and H3K27me3 marks can indirectly influence gene expression through regulatory networks with TF mediation. Thus, our study provides detailed insights into functions of H3K4me3 and H3K27me3 in regulating differential gene expression and subfunctionalization of homeologous genes, therefore serving as a driving force for polyploidization and domestication in cotton.
Real-Time Monitoring of Key Gene Products Involved in Rice Photoperiodic Flowering
Authors: Yoshioka Hayato , Kimura Keiko , Ogo Yuko , Ohtsuki Namie , Nishizawa-Yokoi Ayako , Itoh Hironori , Toki Seiichi , Izawa Takeshi
Published: December 2021

Flowering is an important biological process through which plants determine the timing of reproduction. In rice, florigen mRNA is induced more strongly when the day length is shorter than the critical day length through recognition of 30-min differences in the photoperiod. Grain number, plant height, and heading date 7 (Ghd7), which encodes a CCT-domain protein unique to monocots, has been identified as a key floral repressor in rice, and Heading date 1 (Hd1), a rice ortholog of the Arabidopsis floral activator CONSTANS (CO), is another key floral regulator gene. The Hd1 gene product has been shown to interact with the Ghd7 gene product to form a strong floral repressor complex under long-day conditions. However, the mRNA dynamics of these genes cannot explain the day-length responses of their downstream genes. Thus, a real-time monitoring system of these key gene products is needed to elucidate the molecular mechanisms underlying accurate photoperiod recognition in rice. Here, we developed a monitoring system using luciferase (LUC) fusion protein lines derived from the Ghd7-LUC and Hd1-LUC genes. We successfully obtained a functionally complemented gene-targeted line for Ghd7-LUC. Using this system, we found that the Ghd7-LUC protein begins to accumulate rapidly after dawn and reaches its peak more rapidly under a short-day condition than under a long-day condition. Our system provides a powerful tool for revealing the accurate time-keeping regulation system incorporating these key gene products involved in rice photoperiodic flowering.
Relationship Between the Vascular Bundle Structure of Panicle Branches and the Filling of Inferior Spikelets in Large-Panicle Japonica Rice
Authors: You Cuicui , Wang Hui , Huang Yaru , Xu Peng , Wu Liquan , Yu Fuhan , Zhong Xinyue , Gao Jin , Zhang Liangliang , He Haibing , Ke Jian
Published: December 2021

The vascular bundles of rice panicles serve to connect the source and the sink, as well as serving as a channel for the transportation of materials. In this study, two homozygous japonica rice strains were used as materials. The vascular bundle structures of the branches in different positions within a rice panicle were observed, and their cross-sectional areas were calculated. In addition, the ultrastructure of the central large vascular bundle (LVB) phloem in the rachillae of superior spikelets (SS) and inferior spikelets (IS) was observed during the grain filling period. Moreover, the soluble sugar and protein contents of the SS and IS rachillae were also measured to study whether the differences in the structure of vascular bundles of the branches were related to the plumpness of grain at different positions. The results showed that vascular bundle cross-sectional areas of the basal primary branches were greater than those in the upper primary branches. Moreover, there was little difference in the areas of vascular bundles between the basal secondary branches and upper secondary branches. However, the vascular bundle areas of the IS rachillae were lower than those in the SS rachillae. Therefore, we believe that the poor vascular tissue channel of the IS rachillae could be the limiting factor in IS plumpness. The results also showed that a similar time course in the degradation pattern of some organelles of the sieve elements and companion cells in central LVB was observed in the SS rachillae and IS rachillae during the grain filling period. Compared with the IS rachillae, more abundant mitochondria and plasmodesmata were found in the companion cells of SS rachillae at the beginning of the filling stage, while no significant differences between SS and IS rachillae were identified at the middle and late filling stages, which implies that the SS rachillae were relatively more effective at transportation compared with the IS rachillae at the initial filling stage. Therefore, the undeveloped vascular bundles of the IS rachillae and their poor physiology and lack of ability to transport at the initial filling stages could be the limiting factor in IS plumpness.
Care Ethics Management and Redesign Organization in the New Normal
Authors: Ripamonti Silvio Carlo , Galuppo Laura , Petrilli Sara , Dentali Sharon , Zuffo Riccardo Giorgio
Published: December 2021

The pandemic period has placed the organizations in a state of great tension. It has generated a situation of confusion, lack of rules, and production-related criticalities that have called into question the very existence of many productive realities. This article aims to highlight the dimensions of care and ethics put in place by HR managers in COVID-19. The objective that animated the authors have focused on the HRM level of medium and large companies in Italy to highlight the protective actions toward people and the organization in the period COVID 19, highlighting what were the ethical values and actions of care put in place. In this article, we wanted to give voice to managers (N = 45, including 21 women and 24 men, aged between 40 and 55 years old) who had management tasks in their organizations by asking them to tell us how they dealt with the challenges imposed by the emergency. In the research, we start from a way of understanding workplaces understood as a “process of ongoing social relationship” within which the HR function is dedicated to the care of the quality of relationships. HR managers have to manage a complex role of mediating between the interests of people and employers by trying to find good mediations.