bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovariectomy-induced hormone deprivation aggravates Aβ1-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer’s disease
Authors: Farkas Szidónia , Szabó Adrienn , Török Bibiána , Sólyomvári Csenge , Fazekas Csilla Lea , Bánrévi Krisztina , Correia Pedro , Chaves Tiago , Zelena Dóra
Published: October 2022

Alzheimer’s disease is the most common type of dementia, being highly prevalent in elderly women. The advanced progression may be due to decreased hormone synthesis during post-menopause as estradiol and progesterone both have neuroprotective potentials. We aimed to confirm that female hormone depletion aggravates the progression of dementia in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD). As pathological hallmarks are known to appear in 6-month-old animals, we expected to see disease-like changes in the 4-month-old 3xTg-AD mice only after hormone depletion. Three-month-old female 3xTg-AD mice were compared with their age-matched controls. As a menopause model, ovaries were removed (OVX or Sham surgery). After 1-month recovery, the body composition of the animals was measured by an MRI scan. The cognitive and anxiety parameters were evaluated by different behavioral tests, modeling different aspects (Y-maze, Morris water maze, open-field, social discrimination, elevated plus maze, light–dark box, fox odor, operant conditioning, and conditioned fear test). At the end of the experiment, uterus was collected, amyloid-β accumulation, and the cholinergic system in the brain was examined by immunohistochemistry. The uterus weight decreased, and the body weight increased significantly in the OVX animals. The MRI data showed that the body weight change can be due to fat accumulation. Moreover, OVX increased anxiety in control, but decreased in 3xTg-AD animals, the later genotype being more anxious by default based on the anxiety z-score. In general, 3xTg-AD mice moved less. In relation to cognition, neither the 3xTg-AD genotype nor OVX surgery impaired learning and memory in general. Despite no progression of dementia-like behavior after OVX, at the histological level, OVX aggravated the amyloid-β plaque deposition in the basolateral amygdala and induced early cholinergic neuronal fiber loss in the somatosensory cortex of the transgenic animals. We confirmed that OVX induced menopausal symptoms. Removal of the sexual steroids aggravated the appearance of AD-related alterations in the brain without significantly affecting the behavior. Thus, the OVX in young, 3-month-old 3xTg-AD mice might be a suitable model for testing the effect of new treatment options on structural changes; however, to reveal any beneficial effect on behavior, a later time point might be needed.
Wind-resistant structural optimization of irregular tall building using CFD and improved genetic algorithm for sustainable and cost-effective design
Authors: Alkhatib Fadi , Kasim Narimah , Qaidi Shaker , Najm Hadee Mohammed , Sabri Sabri Mohanad Muayad
Published: October 2022

Tall buildings with irregular shapes and considerable heights are gaining popularity in creating the vertical cities around the world. They also considered one of the major energy consumers with little regards to sustainability. Tall building is wind-sensitive structure and shape plays major role in determining wind loads, which usually govern the design of its lateral resisting system. Thus, evaluating wind loads properly and designing an optimal lateral system accordingly are the main challenges attributed to the design process of irregular tall building. This paper presents a computational procedure for the optimal design of wind-resistant irregular tall building to minimize the total weight of structure within design requirements in single digital environment. That is achieved firstly by creating a digital system of computational fluid dynamic (CFD) analysis that is coupled with pressure-load translation (PLT) algorithm to evaluate the wind motions on irregular tall buildings and generate the design wind loads accordingly. Genetic Algorithm (GA) with enhance design constrains function of lateral displacements, inter-story drifts and top acceleration is then developed to perform structural optimization. A numerical example using 70-story twisting reinforced concrete building is implemented to verify the feasibility of the developed computational procedures. Steady and incompressible flow applied at (0°) angle of attack was implemented in the CFD model to simulate the wind flow on the studied building. Genetic algorithm with improved design constraints of static and dynamic design requirements was developed to optimize the structure effectively and efficiently. The numerical example demonstrates its effectiveness by achieving 35.71% reduction of concrete volume from the original lateral structural system design. This is also translated into a sustainability value by lessening the embedded carbon dioxide by 4,400 tons.
Seasonal distribution of deep groundwater fluoride, geochemical factors and ecological risk for irrigation in the Shendong mining area, China
Authors: Hao Chunming , Wang Yantang , He Kaikai , Gui Herong
Published: October 2022

High-fluoride (F-) deep groundwater in the vicinity of mining areas poses severe ecological risks. In this study, we aimed to characterize and reveal the seasonal distribution and influencing factors of elevated F- concentrations in the deep groundwater in the Shendong mining area, Shaanxi and Inner Mongolia province, China. In addition, the ecological risks associated with F- concentrations in irrigation water were assessed. During the wet and dry seasons, the F- concentrations in mine water samples ranged between 0.12 and 13.92 mg/L (mean: 4.24 mg/L) and between 0.20 and 17.58 mg/L (mean: 4.59 mg/L), respectively. The F- content of mine water was clearly higher during the dry season than that during the wet season. F- concentrations in deep groundwater exhibited consistent spatial distributions during both the dry and wet seasons, with an evident increase from southeast to northwest. The dissolution and precipitation of F--bearing and calcium minerals, cation exchange, competitive adsorption, evaporation, and anthropogenic activities during both the wet and dry seasons were identified as important factors influencing F- concentrations in deep groundwater. In addition, the ecological assessment revealed that 100% and 88.89% of low-F- deep groundwater samples were suitable for practices during the dry and wet seasons, respectively. In contrast 84.00% and 84.62% of high-F- deep groundwater samples were unsuitable for irrigation practices during the dry and wet seasons, respectively. This research provided useful prevention policies of deep groundwater extraction to mitigate environment problems associated with excessive F- irrigation.
Expression of biomarkers connected to endocrine disruption in Cottus gobio and Salmo trutta fario in relation to sewage treatment plant-efflux and pesticides
Authors: Niederwanger Michael , Wieser Josef , Thaler Melanie , Felber Agnes , Schmölz Katja , Mark Wolfgang , Tasser Erich , Kaufmann Rüdiger , Pelster Bernd
Published: October 2022

The increasing efflux on a large scale of organic contaminants holding endocrine disrupting activity from sewage treatment plants produces detrimental biological effects to various fish species. However, the impact of small-scale sewage treatment plant-efflux in small river streams and narrow creeks is largely unknown. Extensive pesticide output especially in vineyards and orchards also causes adverse effects on the endocrine system of wildlife fish species inhabiting nearby rivers. To elaborate whether fish species and populations in the areas of interest were at risk of experiencing endocrine disruption, we identified different biomarkers related to endocrine disruption in Cottus gobio and Salmo trutta fario and applied this approach to selected Austrian freshwater streams pre and post sewage treatment plants and permanent cultures with extensive pesticide output in South Tyrol. Overall, mRNA expression levels of vitellogenin, estrogen receptor α and zona pellucida genes in wildlife fish, compared to a control population reared under constant conditions in the laboratory were significantly increased. Sewage-treatment plant efflux did not significantly affect the mRNA expression levels while extensive use of pesticides altered mRNA expression significantly in C. gobio. C. gobio and S. trutta fario display different levels of mRNA expression. Cadmium and copper concentrations in liver tissues varied but did not indicate significant levels of contamination. Our results demonstrate the presence of endocrine disrupting chemicals in the tested freshwater streams. We anticipate our study to be a starting point for further studies focusing on the effects of endocrine disrupting chemicals on individuals and populations. Especially the fact that the two selected species reveal highly different levels of mRNA expression levels is of interest when applying biomarker approaches which can be a useful tool for monitoring projects and risk-assessment associated studies.
How to coordinate the use and conservation of natural resources in protected areas: From the perspective of tourists’ natural experiences and environmentally responsible behaviours
Authors: Zhang Yuling , Cao Ruibing , Xiao Xiao , Wei Zongcai , Yang Jianbo , Gao Yu’nan , Lu Song , Zheng Chunhui
Published: October 2022

One of the important purposes of opening protected areas to the public is providing tourists with natural experience products and education so as to stimulate their environmentally responsible behaviours (ERBs) and achieve sustainability. However, there are often contradictions between the recreational use of natural resources and eco-environmental protection, and scholars have not directly determined whether natural experiences always trigger tourist ERBs. To fill this gap, we study the formation of ERBs (including environmentally friendly behaviours, environmental concern-based behaviours and sustainable behaviours) by integrating the mechanisms of tourists’ experiences (including sensory experience, mental involvement and norm arousal) and their effects on ERBs. The results of a sample of 682 tourists at a National Nature Reserve in China affirm that there are spillover effects among tourists’ experiences and that tourists’ experiences influence ERBs. Sensory experience and norm arousal positively affect people’s environmentally friendly behaviours, their behaviours that are based on their concern for the environment and their sustainable behaviours. While mental involvement has a positive impact on environmentally friendly behaviours, a negative impact on sustainable behaviours, and no effect on people’s environmental concern-based behaviours. In addition, mental involvement and norm arousal play an important role in mediating the impacts of sensory experience on ERBs. This study explores the relationship between use and conservation of natural resources via tourists’ experiences and ERBs, and it reveals that tourists’ experience stays in mental involvement, which may not conducive to eco-environmental conservation in the protected areas. It opens the field for future research paths in the exploration of the paradox that emerges out of the natural experience and tourists’ ERBs and provides insights into and points to ecological implications for reserve managers and tourism operators.
Multi-model seasonal prediction of global surface temperature based on partial regression correction method
Authors: Yang Yang , Sun Wenbin , Zou Meng , Qiao Shaobo , Li Qingxiang
Published: October 2022

The increased climate change is having a huge impact on the world, with the climatic change sensitive and vulnerable regions at significant risk particularly. Effective understanding and integration of climate information are essential. It helps to reduce the risks associated with adverse weather conditions and to better adapt to the impacts of climate variability and change. Using the hindcast data from Japan Meteorological Agency/Meteorological Research Institute (JMA/MRI) coupled prediction system version 2 (JMA/MRI-CPS2), National Centers for Environmental Prediction (NCEP) Climate Forecast System model version 2 (CFSv2), and Canadian Centre for Climate Modeling and Analysis (CCCma) Coupled Climate Model, versions 3 (CanCM3) seasonal prediction model systems, the performance of seasonal prediction for global surface temperature in boreal summer and winter is comprehensively evaluated and compared for 1982–2011 from the perspective of deterministic and probabilistic forecast skills in this study, and a partial regression correction (PRC) method is introduced to correct seasonal predictions. The results show high prediction skills in the tropics, particularly in the equatorial Pacific, while poor skills on land. In general, JMA/MRI-CPS2 has slightly better prediction performance than CFSv2 and CanCM3 in the tropics. CFSv2 is generally superior to JMA/MRI-CPS2 and CanCM3 in the extratropical northern hemisphere and East Asia, especially for the abnormal low winter temperature prediction in East Asia. CanCM3 shows good deterministic forecast skills in extra-tropics but performs slightly worse in probabilistic forecasting. Based on the respective strengths of each seasonal prediction model, an ensemble forecast correction with observational constraint is implemented by partial regression, and the improvement of skills in ensemble predicting has been analyzed. Compared to the simple multi-model ensemble (MME), the correction improved the global-average temporal correlation coefficient and multi-year mean anomaly correlation coefficient by about 0.1 and 0.13, respectively. The validation tests indicate that the corrected ensemble forecast has higher ranked probability skill scores than that of the MME, which is improved by more than 0.06 in the tropics. Meanwhile, when the training period is sufficiently long, it may have the potential for future seasonal temperature predictions from the perspective of stable zonal partial regression coefficients.
Evaluating green supply chain performance based on ESG and financial indicators
Authors: Zeng Huiling , Li Rita Yi Man , Zeng Liyun
Published: October 2022

To reduce carbon emission and enhance social development simultaneously, “Environmental, Social and Governance” (ESG) plays a significant role in supply chain management. The study collected 2,400 financial data and ESG performance of 200 companies from the Clean 200 list of global public companies from 2019 to 2021. It aimed to: 1) evaluate green supply chain performance based on financial indicators and corporate’s ESG performance; 2) use the entropy weight method (EWM) to determine the weight of ESG elements in green supply chain; 3) validate this ESG-based green supply chain performance using real world examples. The results showed that operational performance had the highest weight, followed by environmental performance, and profitability ranked the last. The results suggested that managers should focus more on the governance and environment rather than emphasizing short-term financial benefits. It contributes to the literature by incorporating ESG to evaluate green supply chain performance, which is the first of its kind. The results would be beneficial when people wish to select supply chain partners. They are also conducive to companies’ managers and listed companies when they submit financial reports that need to report ESG performance.
Genetic and morpho-physiological analyses of the tolerance and recovery mechanisms in seedling stage spring wheat under drought stress
Authors: Ahmed Asmaa A. M. , Dawood Mona F. A. , Elfarash Ameer , Mohamed Elsayed A. , Hussein Mohamed Y. , Börner Andreas , Sallam Ahmed
Published: October 2022

Drought is one of the complex abiotic stresses that affect the growth and production of wheat in arid and semiarid countries. In this study, a set of 172 diverse spring wheat genotypes from 20 different countries were assessed under drought stress at the seedling stage. Besides seedling length, two types of traits were recorded, namely: tolerance traits (days to wilting, leaf wilting, and the sum of leaf wilting), and recovery traits (days to regrowth, regrowth biomass, and drought survival rate). In addition, tolerance index, recovery index, and drought tolerance index (DTI) were estimated to select the most drought tolerant genotypes. Moreover, leaf protein content (P), amino acid (AM), proline content (PRO), glucose (G), fructose (F), and total soluble carbohydrates (TSC) were measured under control and drought conditions to study the changes in each physiological trait due to drought stress. All genotypes showed a high significant genetic variation in all the physio-morphological traits scored under drought stress. High phenotypic and genotypic correlations were found among all seedling morphological traits. Among the studied indices, the drought tolerance index (DTI) had the highest phenotypic and genotypic correlations with all tolerance and recovery traits. The broad-sense heritability (H2) estimates were high for morphological traits (83.85–92.27), while the physiological traits ranged from 96.41 to 98.68 under the control conditions and from 97.13 to 99.99 under drought stress. The averages of the physiological traits (proteins, amino acids, proline, glucose, fructose, and total soluble carbohydrates) denoted under drought stress were higher than those recorded under well-watered conditions except for proteins. In this regard, amino acids, glucose, and total soluble carbohydrates had a significant correlation with all morphological traits. The selection for drought tolerance revealed 10 tolerant genotypes from different countries (8 genotypes from Egypt, one from Morocco, and one from the United States). These selected genotypes were screened for the presence of nine specific TaDREB1 alleles. Six primers were polymorphic among the selected genotypes. Genetic diversity among the selected genotypes was investigated using 21,450 SNP markers. The results of the study shed light on the different mechanisms for drought tolerance that wheat plants use to tolerate and survive under drought stress. The genetic analysis performed in this study suggested the most suitable genotypes for selective breeding at the seedling stage under water deficit.
Epigenome-wide association study of biomarkers of liver function identifies albumin-associated DNA methylation sites among male veterans with HIV
Authors: Titanji Boghuma K. , Lee Mitch , Wang Zeyuan , Chen Junyu , Hui Qin , Lo Re III Vincent , So-Armah Kaku , Justice Amy C. , Xu Ke , Freiberg Matthew , Gwinn Marta , Marconi Vincent C. , Sun Yan V.
Published: October 2022

Background: Liver disease (LD) is an important cause of morbidity and mortality for people with HIV (PWH). The molecular factors linked with LD in PWH are varied and incompletely characterized. We performed an epigenome-wide association study (EWAS) to identify associations between DNA methylation (DNAm) and biomarkers of liver function—aspartate transaminase, alanine transaminase, albumin, total bilirubin, platelet count, FIB-4 score, and APRI score—in male United States veterans with HIV.

Methods: Blood samples and clinical data were obtained from 960 HIV-infected male PWH from the Veterans Aging Cohort Study. DNAm was assessed using the Illumina 450K or the EPIC 850K array in two mutually exclusive subsets. We performed a meta-analysis for each DNAm site measured by either platform. We also examined the associations between four measures of DNAm age acceleration (AA) and liver biomarkers.

Results: Nine DNAm sites were positively associated with serum albumin in the meta-analysis of the EPIC and 450K EWAS after correcting for multiple testing. Four DNAm sites (cg16936953, cg18942579, cg01409343, and cg12054453), annotated within the TMEM49 and four of the remaining five sites (cg18181703, cg03546163, cg20995564, and cg23966214) annotated to SOCS3, FKBP5, ZEB2, and SAMD14 genes, respectively. The DNAm site, cg12992827, was not annotated to any known coding sequence. No significant associations were detected for the other six liver biomarkers. Higher PhenoAA was significantly associated with lower level of serum albumin (β = -0.007, p-value = 8.6 × 10–4, CI: -0.011116, -0.002884).

Conclusion: We identified epigenetic associations of both individual DNAm sites and DNAm AA with liver function through serum albumin in men with HIV. Further replication analyses in independent cohorts are warranted to confirm the epigenetic mechanisms underlying liver function and LD in PWH.
Prognostic significance of modified lung immune prognostic index in osteosarcoma patients
Authors: He Xuanhong , Tang Fan , Zou Chang , Li Longqing , Wang Yang , Kenmegne Guy Romeo , Zhou Yong , Lu Minxun , Min Li , Luo Yi , Tu Chongqi
Published: October 2022

Purpose: Osteosarcoma is the most common primary malignancy of bone with a dismal prognosis for patients with pulmonary metastases. Evaluation of osteosarcoma prognosis would facilitate the prognosis consultation as well as the development of personalized treatment decisions. However, there is limited effective prognostic predictor at present. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers, whereas, the prognostic significance of LIPI in osteosarcoma has not yet been well clarified. In this study, we firstly explore the prognostic role of LIPI and further modify this predictive model in osteosarcoma.

Patients and methods: A retrospectively study was conducted at Musculoskeletal Tumor Center of West China Hospital between January 2016 and January 2021. Hematological factors and clinical features of osteosarcoma patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated.

Results: In this study, lactate dehydrogenase (LDH), derived neurtrophil to lymphocyte ratio (dNLR), and Hydroxybutyrate dehydrogenase (HBDH) have higher AUC values. LIPI was composed of LDH and dNLR and was further modified by combing the HBDH, forming the osteosarcoma immune prognostic index (OIPI). OIPI divided 223 osteosarcoma patients divided into four groups, none, light, moderate, and severe (p < 0.0001). OIPI has a higher AUC value than LIPI and other hematological indexes in t-ROC curve. According to the univariate and multivariate analysis, pathological fracture, metastasis, NLR, platelet–lymphocyte ratio (PLR), and OIPI were associated with the prognosis; and metastasis and OIPI were independent prognostic factors of osteosarcoma patients. An OIPI-based nomogram was also established and could predict the 3-year and 5-year overall survival. In addition, OIPI was also revealed correlated with metastasis and pathological fracture in osteosarcoma.

Conclusion: This study first explore the prognostic significance of LIPI in osteosarcoma patients. In addition, we developed a modified LIPI, the OIPI, for osteosarcoma patients. Both the LIPI and OIPI could predict the overall survival of osteosarcoma patients well, while OIPI may be more suitable for osteosarcoma patients. In particular, OIPI may have the ability to identify some high-risk patients from clinically low-risk patients.
Whole genome bisulfite sequencing reveals DNA methylation roles in the adaptive response of wildness training giant pandas to wild environment
Authors: Jie Xiaodie , Wu Honglin , Yang Miao , He Ming , Zhao Guangqing , Ling Shanshan , Huang Yan , Yue Bisong , Yang Nan , Zhang Xiuyue
Published: October 2022

DNA methylation modification can regulate gene expression without changing the genome sequence, which helps organisms to rapidly adapt to new environments. However, few studies have been reported in non-model mammals. Giant panda (Ailuropoda melanoleuca) is a flagship species for global biodiversity conservation. Wildness and reintroduction of giant pandas are the important content of giant pandas’ protection. However, it is unclear how wildness training affects the epigenetics of giant pandas, and we lack the means to assess the adaptive capacity of wildness training giant pandas. We comparatively analyzed genome-level methylation differences in captive giant pandas with and without wildness training to determine whether methylation modification played a role in the adaptive response of wildness training pandas. The whole genome DNA methylation sequencing results showed that genomic cytosine methylation ratio of all samples was 5.35%–5.49%, and the methylation ratio of the CpG site was the highest. Differential methylation analysis identified 544 differentially methylated genes (DMGs). The results of KEGG pathway enrichment of DMGs showed that VAV3, PLCG2, TEC and PTPRC participated in multiple immune-related pathways, and may participate in the immune response of wildness training giant pandas by regulating adaptive immune cells. A large number of DMGs enriched in GO terms may also be related to the regulation of immune activation during wildness training of giant pandas. Promoter differentially methylation analysis identified 1,199 genes with differential methylation at promoter regions. Genes with low methylation level at promoter regions and high expression such as, CCL5, P2Y13, GZMA, ANP32A, VWF, MYOZ1, NME7, MRPS31 and TPM1 were important in environmental adaptation for wildness training giant pandas. The methylation and expression patterns of these genes indicated that wildness training giant pandas have strong immunity, blood coagulation, athletic abilities and disease resistance. The adaptive response of giant pandas undergoing wildness training may be regulated by their negatively related promoter methylation. We are the first to describe the DNA methylation profile of giant panda blood tissue and our results indicated methylation modification is involved in the adaptation of captive giant pandas when undergoing wildness training. Our study also provided potential monitoring indicators for the successful reintroduction of valuable and threatened animals to the wild.
Exploring metabolism in scleroderma reveals opportunities for pharmacological intervention for therapy in fibrosis
Authors: Cantanhede Isabella Gomes , Liu Huan , Liu Huan , Balbuena Rodriguez Vestaen , Shiwen Xu , Ong Voo H. , Denton Christopher P. , Ponticos Markella , Xiong Guo , Lima-Filho José Luiz , Abraham David , Abu-Hanna Jeries , Taanman Jan-Willem
Published: October 2022

Background

Recent evidence has indicated that alterations in energy metabolism play a critical role in the pathogenesis of fibrotic diseases. Studies have suggested that ‘metabolic reprogramming’ involving the glycolysis and oxidative phosphorylation (OXPHOS) in cells lead to an enhanced generation of energy and biosynthesis. The aim of this study was to assess the molecular basis of changes in fibrotic metabolism in systemic sclerosis (Scleroderma; SSc) and highlight the most appropriate targets for anti-fibrotic therapies.

Materials and methods

Dermal fibroblasts were isolated from five SSc patients and five healthy donors. Cells were cultured in medium with/without TGF-β1 and with/without ALK5, pan-PIM or ATM kinase inhibitors. Extracellular flux analyses were performed to evaluate glycolytic and mitochondrial respiratory function. The mitochondrial network in TMRM-stained cells was visualized by confocal laser-scanning microscopy, followed by semi-automatic analysis on the ImageJ platform. Protein expression of ECM and fibroblast components, glycolytic enzymes, subunits of the five OXPHOS complexes, and dynamin-related GTPases and receptors involved in mitochondrial fission/fusion were assessed by western blotting.

Results

Enhanced mitochondrial respiration coupled to ATP production was observed in SSc fibroblasts at the expense of spare respiratory capacity. Although no difference was found in glycolysis when comparing SSc with healthy control fibroblasts, levels of phophofructokinase-1 isoform PFKM were significantly lower in SSc fibroblasts (P<0.05). Our results suggest that the number of respirasomes is decreased in the SSc mitochondria; however, the organelles formed a hyperfused network, which is thought to increase mitochondrial ATP production through complementation. The increased mitochondrial fusion correlated with a change in expression levels of regulators of mitochondrial morphology, including decreased levels of DRP1, increased levels of MIEF2 and changes in OPA1 isoform ratios. TGF-β1 treatment strongly stimulated glycolysis and mitochondrial respiration and induced the expression of fibrotic markers. The pan-PIM kinase inhibitor had no effect, whereas both ALK5 and ATM kinase inhibition abrogated TGF-β1-mediated fibroblast activation, and upregulation of glycolysis and respiration.

Conclusions

Our data provide evidence for a novel mechanism(s) by which SSc fibroblasts exhibit altered metabolic programs and highlight changes in respiration and dysregulated mitochondrial morphology and function, which can be selectively targeted by small molecule kinase inhibitors.
Comparing the B and T cell-mediated immune responses in patients with type 2 diabetes receiving mRNA or inactivated COVID-19 vaccines
Authors: Lee Chi-Ho , Gray Victor , Teo Jia Ming Nickolas , Tam Anthony Raymond , Fong Carol Ho-Yi , Lui David Tak-Wai , Pang Polly , Chan Kwok Hung , Hung Ivan Fan-Ngai , Tan Kathryn Choon-Beng , Ling Guang Sheng
Published: October 2022

Acquiring protective immunity through vaccination is essential, especially for patients with type 2 diabetes who are vulnerable for adverse clinical outcomes during coronavirus disease 2019 (COVID-19) infection. Type 2 diabetes (T2D) is associated with immune dysfunction. Here, we evaluated the impact of T2D on the immunological responses induced by mRNA (BNT162b2) and inactivated (CoronaVac) vaccines, the two most commonly used COVID-19 vaccines. The study consisted of two parts. In Part 1, the sera titres of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) alpha receptor binding domain (RBD), their neutralizing capacity, and antigen-specific CD4+T and CD8+T cell responses at 3-6 months after vaccination were compared between BNT162b2 (n=60) and CoronaVac (n=50) vaccinees with or without T2D. Part 2 was a time-course study investigating the initial B and T cell responses induced by BNT162b2 among vaccinees (n=16) with or without T2D. Our data showed that T2D impaired both cellular and humoral immune responses induced by CoronaVac. For BNT162b2, T2D patients displayed a reduction in CD4+T-helper 1 (Th1) differentiation following their first dose. However, this initial defect was rectified by the second dose of BNT162b2, resulting in comparable levels of memory CD4+ and CD8+T cells, anti-RBD IgG, and neutralizing antibodies with healthy individuals at 3-6 months after vaccination. Hence, T2D influences the effectiveness of COVID-19 vaccines depending on their platform. Our findings provide a potential mechanism for the susceptibility of developing adverse outcomes observed in COVID-19 patients with T2D and received either CoronaVac or just one dose of BNT162b2.
Describing immune factors associated with Hepatitis B surface antigen loss: A nested case-control study of a Chinese sample from Wuwei City
Authors: Yuan Xiaojie , Fu Ting , Xiao Lixin , He Zhen , Ji Zhaohua , Seery Samuel , Zhang Wenhua , Ye Yancheng , Zhou Haowei , Kong Xiangyu , Zhang Shuyuan , Zhou Qi , Lin Yulian , Jia Wenling , Liang Chunhui , Tang Haitao , Wang Fengmei , Zhang Weilu , Shao Zhongjun
Published: October 2022

Background

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure for chronic hepatitis B (CHB), however, several factors influence HBsAg loss.

Methods

29 CHB patients who had achieved HBsAg loss, were selected and 58 CHB patients with persistent HBsAg were matched, according to gender and age (+/- 3 years). Logistic regression and restricted cubic spline (RCS) modelling were performed.

Results

Multivariate-adjusted logistic regression, based on stepwise selection, showed that baseline HBsAg levels negatively correlated with HBsAg loss (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.98-0.99). Interferon treatment positively related with HBsAg loss (OR = 7.99, 95%CI = 1.62-44.88). After adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment, MMP-1 (OR = 0.66, 95%CI = 0.44-0.97), CXCL9 (OR = 0.96, 95%CI = 0.93-0.99) and TNF-R1 (OR = 0.97, 95%CI = 0.94-0.99) baseline levels all negatively correlated with HBsAg loss. Our multivariate-adjusted RCS model showed that baseline CXCL10 was associated with HBsAg loss although the relationship was “U-shaped”.

Conclusions

Cytokines such as MMP-1, CXCL9, CXCL10 and TNF-R1 are important factors which influence HBsAg loss. It may be possible to develop a nomogram which intercalates these factors; however, further research should consider immune processes involved in HBsAg loss.
Development and validation of four ferroptosis-related gene signatures and their correlations with immune implication in hepatocellular carcinoma
Authors: Zhang Ying , Ren He , Zhang Chunting , Li Haihua , Guo Qingzhi , Xu Haitao , Cui Lina
Published: October 2022

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This tumor presents with an insidious onset, rapid progression, and frequent recurrence. Ferroptosis is a newly discovered mode of programmed cell death that may play a key role in the progression of HCC. This study aimed to investigate the prognostic value of ferroptosis-related genes (FRGs) in HCC and their impact on tumor immune function, thereby providing new insights into targeted therapy for HCC. First, 43 differentially expressed FRGs were identified using the TCGA database, and four prognostically relevant methylation-driven FRGs (G6PD, HELLS, RRM2, and STMN1) were screened via survival and methylation analyses. Gene co-expression, mutation, and clinicopathological characterization indicated that these four pivotal FRGs play essential roles in tumor progression. We also validated these four genes using transcriptomic and proteomic data as well as cohort samples from our patients. Moreover, receiver operator characteristic (ROC) curves confirmed that the signatures of the four FRGs were independent prognostic factors in HCC. Gene set enrichment analysis of the four FRGs showed statistically significant associations with pathways related to HCC proliferation. Finally, the TIMER and TISIDB databases indicated that the four FRGs were statistically significantly correlated with tumor-infiltrating immune cells and immune checkpoint expression. Taken together, this study provides information guiding a novel therapeutic strategy targeting FRGs for HCC treatment.
Characterization of cardiac bradyarrhythmia associated with LGI1-IgG autoimmune encephalitis
Authors: Zhao-Fleming Hannah H. , Zahid Anza , Lu Tong , Sun Xiaojing , Pittock Sean J. , Lee Hon-Chi , Dubey Divyanshu
Published: October 2022

Objective

To evaluate and characterize cardiac arrythmias associated with LGI1-IgG (Leucine-rich glioma inactivated 1–IgG) autoimmune encephalitis (AE).

Patients and methods

In this retrospective descriptive study, we identified Mayo Clinic patients (May 1, 2008 – December 31, 2020) with LGI1-IgG AE who had electrocardiogram proven bradyarrhythmias during the initial presentation. Inclusion criteria were 1) LGI1-IgG positivity with a consistent clinical syndrome; 2) electrocardiographic evidence of bradyarrhythmia; and 3) sufficient clinical details. We excluded patients who were taking negative ionotropic agents at the time of their bradyarrhythmias. We collected demographic/clinical data including details of bradyarrhythmia (severity, duration, treatments), and neurologic and cardiac outcomes.

Results

We found that patients with LGI1-IgG AE had bradyarrhythmia at a frequency of 8% during the initial presentation. The bradyarrhythmia was often asymptomatic (6/11, 55%); however, the episode was severe with one patient requiring a pacemaker. Outcome was also generally favorable with the majority (8/11, 73%) having full resolution without further cardiac intervention. Lastly, we found that mouse and human cardiac tissues express LGI1 (mRNA and protein).

Conclusion

LGI1-IgG AE can be rarely associated with bradyarrhythmias. Although the disease course is mostly favorable, some cases may require pacemaker placement to avoid devastating outcomes.
Ferroptosis and musculoskeletal diseases: “Iron Maiden” cell death may be a promising therapeutic target
Authors: Zhang Yili , Huang Xinyi , Qi Baoyu , Sun Chuanrui , Sun Kai , Liu Ning , Zhu Liguo , Wei Xu
Published: October 2022

Ferroptosis is a novel form of cell death precisely regulated by iron metabolism, antioxidant processes, and lipid metabolism that plays an irreplaceable role in the development of many diseases. Musculoskeletal disorders (MSKs), including osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, sarcopenia, and rhabdomyolysis, have become one of the most common causes of disability and a major burden on public health and social care systems. The mechanism of ferroptosis in MSKs has recently been elucidated. In this review, we briefly introduce the ferroptosis mechanism and illustrate the pathological roles of ferroptosis in MSKs with a focus on how ferroptosis can be exploited as a promising treatment strategy. Notably, because the toxicity of compounds that inhibit or induce ferroptosis in other organs is largely unknown, ferroptosis appears to be a double-edged sword. We point out that more research is needed in the future to verify the therapeutic effects based on ferroptosis in MSKs.
Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury
Authors: Fan Zuyan , Gao Yan , Jiang Nan , Zhang Fengxia , Liu Shuangxin , Li Quhuan
Published: October 2022

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and has become a serious medical issue globally. Although it is known to be associated with glomerular injury, tubular injury has been found to participate in DN in recent years. However, mechanisms of diabetic renal tubular injury remain unclear. Here, we investigated the differentially expressed genes in the renal tubules of patients with DN by analyzing three RNA-seq datasets downloaded from the Gene Expression Omnibus database. Gene set enrichment analysis and weighted gene co-expression network analysis showed that DN is highly correlated with the immune system. The immune-related gene SERPINA3 was screened out with lasso regression and Kaplan–Meier survival analyses. Considering that SERPINA3 is an inhibitor of mast cell chymase, we examined the expression level of SERPINA3 and chymase in human renal tubular biopsies and found that SERPINA3 was upregulated in DN tubules, which is consistent with the results of the differential expression analysis. Besides, the infiltration and degranulation rates of mast cells are augmented in DN. By summarizing the biological function of SERPINA3, chymase, and mast cells in DN based on our results and those of previous studies, we speculated that SERPINA3 is a protective immune-related molecule that prevents renal tubular injury by inhibiting the proliferation and activation of mast cells and downregulating the activity of chymase.
Renewal of seasonally anoxic Saanich Inlet is temporally and spatially dynamic
Authors: Soetaert Grayson , Hamme Roberta C. , Raftery Erinn
Published: October 2022

Injection of oxygenated water into anoxic basins sets off a cascade of biogeochemical reactions and ecosystem shifts. The dynamic nature of these events can create spatial variability in the resulting water mass that strongly affects subsequent observations. Their irregularity can also make their prediction for experiment planning challenging. Our study focuses on Saanich Inlet, one of the most accessible and well-studied anoxic basins in the world. In the late summer and early fall, dense water can cross the sill into this fjord, in discrete events, bringing oxygen and nitrate to the deep waters of the inlet. We assess the potential strength of these renewal events using density measured at a bottom mooring on the sill. We find that the occurrence and potential strength of renewals is primarily controlled by tidal current speeds, which can be well predicted. However, the intensity of coastal upwelling, which brings dense water into the estuarine system, plays a significant secondary control, reducing predictability. We also demonstrate that renewals do not result in a homogeneous water mass filling the deep inlet. Instead, high frequency measurements from a profiling mooring in the centre of the inlet reveal that different densities intruding over the several-day renewal period create a complex layering of waters containing different proportions of new oxic and old anoxic waters. Finally, we show that not every instance of high density water observed over the sill results in flushing of the deepest waters inside the inlet. We hypothesize that each renewal improves the chance of a subsequent renewal in the same season by reducing the density contrast between waters entering and already inside the inlet. Consideration of the temporal and spatial complexity of these renewal dynamics is necessary to support studies using Saanich Inlet as a natural laboratory for exploring oxygen deficient systems.
The spatial-temporal consistency of chlorophyll-a and fishery resources in the water of the Zhoushan archipelago revealed by high resolution remote sensing
Authors: Cai Lina , Tang Rong , Yan Xiaojun , Zhou Yongdong , Jiang Jingjing , Yu Menghan
Published: October 2022

Details of the chlorophyll-a (Chl-a) distribution in the water of the Zhoushan archipelago were analyzed based on data from the panchromatic multispectral sensor (PMS) of the GaoFen-6 (GF-6). A new Chl-a inversion model was built using in-situ Chl-a and the green-red bands of the 2 m spatial resolution GF-6/PMS image. Combined with fishery data, the relationship between Chl-a concentration and fish resources were revealed. The results show that: (1) High Chl-a concentration area was mainly concentrated in the nearshore intensive islands waters, and Chl-a concentration changes obviously with the change of tidal currents. Chl-a concentration around islands increases, especially downstream of islands. Seasonally, Chl-a concentration is higher in spring and summer, lower in autumn, and lowest in winter. (2) The change of fish eggs and larvae in the water of the Zhoushan archipelago shows consistency with the spatial distribution and seasonal variation of Chl-a. (3) The interaction between tidal currents and islands results in the diverse currents (upstream upwelling and downstream vortex currents) around the islands, promoting vertical water exchange and the uplifting of nutrients, resulting in a high overall Chl-a concentration in the waters around the islands. The diverse flow conditions, the ideal nutrient-rich environment, and the abundant phytoplankton attract a large number of fish to gather and breed in the waters around the islands. (4) Chl-a of intensive island waters is an essential indicator for fish spawning grounds.
Borderless conservation: Integrating connectivity into high seas conservation efforts for the Salas y Gómez and Nazca ridges
Authors: Boteler Ben , Wagner Daniel , Durussel Carole , Stokes Emily , Gaymer Carlos F. , Friedlander Alan M. , Dunn Daniel C. , Vargas Felipe Paredes , Veliz David , Hazin Carolina
Published: October 2022

Connectivity is essential to consider in area-based marine conservation measures because it greatly impacts vital ecological processes (e.g., recycling nutrients, regulating temperature, sequestering carbon, and supporting the life cycle of species). However, it is generally not well studied or integrated into conservation measures, particularly in the Southeast Pacific. This region is home to the Salas y Gómez and Nazca ridges, two adjacent seamount chains that stretch between the Peruvian coast and Rapa Nui (i.e., Easter Island). The area has been recognized for its exceptional natural and cultural significance as well as one of the most important global areas to protect. However, over 73% of the ridges are in areas beyond national jurisdiction, where they are unprotected and under threat. This study provides a synthesis of what we know about connectivity in the Salas y Gómez and Nazca ridges and provides practical recommendations for integrating this knowledge into conservation and management measures for the region. While data on connectivity is still limited, it should not constrain the development of conservation measures, which should be co-designed and co-developed, leveraging the expertise of international working groups throughout the region. Due to their high rates of endemism, as well as importance as migratory corridors, enacting large-scale conservation measures would address important conservation considerations for both connectivity and endemism. Enacting such large-scale conservation measures would not only elevate the Salas y Gómez and Nazca ridges as an exemplary case study, providing lessons for other marine regions seeking to implement similar measures, but could also help raise awareness on the severity of externally originating threats like climate change and plastic pollution to global audiences.
Fire resistance of composite shear walls filled with demolished concrete lumps and self-compacting concrete
Authors: Xiong Yan , Chen Yaxin , Wu Bo , Zhao Guowei
Published: October 2022

The recycling and reuse of waste concrete is conducive to promoting the sustainable development of resources and practicing the concept of green development. Demolished concrete lumps (DCLs) and self-compacting concrete (SCC) made from waste concrete take full advantage of their recyclability. In order to fully utilize the advantages of demolished concrete lumps and self-compacting concrete in construction, applying demolished concrete lumps and self-compacting concrete to composite shear wall structures is an effective way to reduce costs and improve industrial production. In this paper, a new composite shear wall filled with demolished concrete lumps and self-compacting concrete is proposed, and its fire performance is investigated. The shear wall combines edge constraints of concrete-filled steel tubes, demolished concrete lumps and self-compacting concrete. In order to facilitate the mass pouring of demolished concrete lumps, a cavity is formed between the steel tubes at the ends and the precast walls on both sides. A double-sided fire tests was conducted on three composite shear wall specimens filled with demolished concrete lumps and self-compacting concrete at a constant axial compression ratio, where the fire-retardant coating and the wall width-to-depth ratio were considered as the main test parameters. The specimens were able to steadily withstand the predetermined axial loads during the fire resistance time of 180 min and showed good fire resistance. The concrete temperature variation trends of the three specimens in the wall section were basically the same. The fire-retardant coating on the concealed column had a significant effect on the section temperature of the steel tube, while increasing the wall width-to-depth ratio had little effect. When the axial compression ratio was 0.19, the specimens were in the expansion stage within 180 min and no compression occurred. The results show that the expansion deformation of the shear wall sprayed with fire-retardant coating on the outer surface of the concealed column is smaller than that of the shear wall without fire-retardant coating, and the axial deformation of the composite shear wall infilled with demolished concrete lumps and self-compacting concrete is not affected by increasing the wall width-to-depth ratio.