bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of physical activity and cardiorespiratory fitness with β-cell dysfunction, insulin resistance, and diabetes among adults in north-western Tanzania: A cross-sectional study
Authors: Kitilya Brenda , Peck Robert , Changalucha John , Jeremiah Kidola , Kavishe Bazil B. , Friis Henrik , Filteau Suzanne , Krogh-Madsen Rikke , Brage Soren , Faurholt-Jepsen Daniel , Olsen Mette F. , PrayGod George
Published: August 2022

Introduction

Research on the associations of physical activity and cardiorespiratory fitness with β-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with β-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults.

Method

In a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess β-cell dysfunction (defined as insulinogenic index <0.71 (mU/L)/(mmol/L), HOMA-β index <38.3 (mU/L)/(mmol/L), and overall insulin release index <33.3 (mU/L)/(mmol/L)), oral disposition index <0.16 (mU/L)/(mg/dL)(mU/L)-1, insulin resistance (HOMA-IR index >1.9 (mU/L)/(mmol/L) and Matsuda index <7.2 (mU/L)/(mmol/L), prediabetes and diabetes which were the dependent variables. Physical activity energy expenditure (PAEE), sleeping heart rate (SHR), and maximum uptake of oxygen during exercise (VO2 max) were the independent variables and were assessed using a combined heart rate and accelerometer monitor. Logistic regressions were used to assess the associations.

Results

Of 391 participants, 272 were PLWH and 119 HIV-uninfected. The mean age was 39 ( ± 10.5) years and 60% (n=235) were females. Compared to lower tertile, middle tertile of PAEE was associated with lower odds of abnormal insulinogenic index (OR=0.48, 95%CI: 0.27, 0.82). A 5 kj/kg/day increment of PAEE was associated with lower odds of abnormal HOMA-IR (OR=0.91, 95%CI: 0.84, 0.98), and reduced risk of pre-diabetes (RRR=0.98, 95%CI: 0.96, 0.99) and diabetes (RRR=0.92, 95%CI: 0.88, 0.96). An increment of 5 beats per min of SHR was associated with higher risk of diabetes (RRR=1.06, 95%CI: 1.01, 1.11). An increase of 5 mLO2/kg/min of VO2 max was associated with lower risk of pre-diabetes (RRR=0.91, 95%CI: 0.86, 0.97), but not diabetes. HIV status did not modify any of these associations (interaction, p>0.05).

Conclusion

Among Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with β-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve β-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA.
Causal associations between body fat accumulation and COVID-19 severity: A Mendelian randomization study
Authors: Yoshiji Satoshi , Tanaka Daisuke , Minamino Hiroto , Lu Tianyuan , Butler-Laporte Guillaume , Murakami Takaaki , Fujita Yoshihito , Richards J. Brent , Inagaki Nobuya
Published: August 2022

Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height and weight and cannot distinguish between body fat mass and fat-free mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Here, we used Mendelian randomization (MR) to compare the independent causal relationships of body fat mass and fat-free mass with COVID-19 severity. We identified single nucleotide polymorphisms associated with body fat mass and fat-free mass in 454,137 and 454,850 individuals of European ancestry from the UK Biobank, respectively. We then performed two-sample MR to ascertain their effects on severe COVID-19 (cases: 4,792; controls: 1,054,664) from the COVID-19 Host Genetics Initiative. We found that an increase in body fat mass by one standard deviation was associated with severe COVID-19 (odds ratio (OR)body fat mass = 1.61, 95% confidence interval [CI]: 1.28–2.04, P = 5.51 × 10-5; ORbody fat-free mass = 1.31, 95% CI: 0.99–1.74, P = 5.77 × 10-2). Considering that body fat mass and fat-free mass were genetically correlated with each other (r = 0.64), we further evaluated independent causal effects of body fat mass and fat-free mass using multivariable MR and revealed that only body fat mass was independently associated with severe COVID-19 (ORbody fat mass = 2.91, 95% CI: 1.71–4.96, P = 8.85 × 10-5 and ORbody fat-free mass = 1.02, 95%CI: 0.61–1.67, P = 0.945). In summary, this study demonstrates the causal effects of body fat accumulation on COVID-19 severity and indicates that the biological pathways influencing the relationship between COVID-19 and obesity are likely mediated through body fat mass.
Case report: Corticosteroids-induced acute diabetic peripheral neuropathy
Authors: Yuan Jia-Lin , Sun Le , Su Bao-Lin , Hong Chuang-Xiong
Published: August 2022

A 62-year-old man was diagnosed as IgA nephropathy. He had a pancreatic tumor operation 19 years ago and had a normal plasma glucose test every year. One month after the medication of prednisolone acetate was administered his fasting plasma glucose elevated to 7.1mmol/L while he manifested symptoms of thirst, frequent urination, and weight loss. Approximately 3 months after the steroids, he started complaining of numbness, weakness, and muscle cramp in his lower extremities, blood tests showed elevated plasma glucose and electromyography (EMG) revealed impairment of the peripheral nerves in the lower extremity, diabetic peripheral neuropathy was diagnosed. Mecobalamin and Acupuncture were employed and steroids were discontinued, 8 months later he recovered part of his strength and sensation. This case presents a specific adverse drug reaction of corticosteroids that causes diabetes mellitus and subsequently leads to peripheral neuropathy in an acute onset.
A Bayesian network model of new-onset diabetes in older Chinese: The Guangzhou biobank cohort study
Authors: Wang Ying , Zhang Wei Sen , Hao Yuan Tao , Jiang Chao Qiang , Jin Ya Li , Cheng Kar Keung , Lam Tai Hing , Xu Lin
Published: August 2022

Background

Existing diabetes risk prediction models based on regression were limited in dealing with collinearity and complex interactions. Bayesian network (BN) model that considers interactions may provide additional information to predict risk and infer causation.

Methods

BN model was constructed for new-onset diabetes using prospective data of 15,934 participants without diabetes at baseline [73% women; mean (standard deviation) age = 61.0 (6.9) years]. Participants were randomly assigned to a training (n = 12,748) set and a validation (n = 3,186) set. Model performances were assessed using area under the receiver operating characteristic curve (AUC).

Results

During an average follow-up of 4.1 (interquartile range = 3.3–4.5) years, 1,302 (8.17%) participants developed diabetes. The constructed BN model showed the associations (direct, indirect, or no) among 24 risk factors, and only hypertension, impaired fasting glucose (IFG; fasting glucose of 5.6–6.9 mmol/L), and greater waist circumference (WC) were directly associated with new-onset diabetes. The risk prediction model showed that the post-test probability of developing diabetes in participants with hypertension, IFG, and greater WC was 27.5%, with AUC of 0.746 [95% confidence interval CI) = 0.732–0.760], sensitivity of 0.727 (95% CI = 0.703–0.752), and specificity of 0.660 (95% CI = 0.652–0.667). This prediction model appeared to perform better than a logistic regression model using the same three predictors (AUC = 0.734, 95% CI = 0.703–0.764, sensitivity = 0.604, and specificity = 0.745).

Conclusions

We have first reported a BN model in predicting new-onset diabetes with the smallest number of factors among existing models in the literature. BN yielded a more comprehensive figure showing graphically the inter-relations for multiple factors with diabetes than existing regression models.
IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma
Authors: Liu Zhihui , Ji Hang , Fu Wenchao , Ma Shuai , Zhao Hongtao , Wang Fang , Dong Jiawei , Yan Xiuwei , Zhang Jiheng , Wang Nan , Wu Jiasheng , Hu Shaoshan
Published: August 2022

Background

The IGFBP family of insulin-like growth factor binding proteins has important biological functions in the organism. However, the role of the IGFBP family in low-grade glioma (LGG) has not been fully explored.

Methods

We validated the clinical value of the IGFBP family using RNA-seq and clinical data of LGG in the TCGA and constructed an IGFBPScore using LASSO-regression analysis for prognosis prediction, subtype determination, and treatment sensitivity determination. Subsequently, we explored the role of the IGFBP family in the development of LGG using PanCanAtlas data.

Results

Our results suggest that most IGFBP family members were aberrantly expressed and were strongly associated with poor prognosis in LGG. By constructing an IGFBPScore representing the IGFBP family, we found that tumor samples with a high IGFBPScore had a glioblastoma-like mutation pattern characterized by IDH1wt, EGFRmut, PTENmut, and NF1mut with hypo-methylation and glioma stem cell (GSC) diversity. In contrast, the low IGFBPScore group was characterized by IDH1mut accompanied by TP53mut, CICmut, and ATRXmut, and had hyper-methylation status as well as the GSC restriction. Additionally, the high-IGFBPScore group had a high inflammation phenotype with increased immune antigenicity and increased infiltration of immune molecules and cells, as well as a high extracellular matrix phenotype and enhanced multiple metabolic pathways compared with the immune-quiet phenotype of the low-IGFBPScore group, which was strongly associated with poor prognosis.

Conclusion

Our study provides a summary analysis and a theoretical basis for the biological role and clinical value of the IGFBP family in LGG, providing an important therapeutic target for LGG.
Land Use Zoning Management to Coordinate the Supply–Demand Imbalance of Ecosystem Services: A Case Study in the City Belt Along the Yellow River in Ningxia, China
Authors: Lyu Rongfang , Clarke Keith C. , Tian Xiaolei , Zhao Wenpeng , Pang Jili , Zhang Jianming
Published: August 2022

The imbalance between the supply and demand of ecosystem services (ESs) is one of the main reasons for ecological degradation, which significantly impacts human well-being and ecological safety. Spatial heterogeneity of ES supply–demand, ES tradeoffs, and the socioecological environment calls for zoning management, while few studies have combined the above three aspects in dividing management zones and proposed strategies. Using the City Belt along the Yellow River in Ningxia in northwestern China as a case study, this study quantified the supply and demand for five key ESs (crop production, carbon sequestration, nutrient retention, sand fixation, and recreational opportunity), analyzed ES tradeoffs/synergies and bundles through correlation analysis and the self-organizing map (SOM) method, and investigated their socioecological driving mechanisms through a random forest model and the SOM method. Management zones were proposed and differentiated suggestions were provided through overlaying ES bundles and driver clusters. The results suggested that crop production, carbon sequestration, and nutrient retention mostly correlated to the same intrinsic ecological process, resulting in consistent synergies among these three ESs at both supply and demand sides. On the contrary, the variance in interactions between the two ESs of sand fixation and recreational opportunity and the other three ESs is due to the low similarity of their intrinsic ecological processes and external driving mechanisms. Fourteen socioecological factors could effectively explain the spatial heterogeneity of ES supply, demand, and match degree. Fourteen management zones with similar ecological problems and socioecological environments were delineated, and differentiated suggestions were provided for each zone. Adopting both ES characteristics and the socioecological environment into zoning management could effectively detect ecological problems and help to promote management suggestions in different socioecological contexts. This framework could offer new insights for integrating ESs into actual decision-making and ecosystem management.
Drivers of the European Union’s Environmental Performance
Authors: Stoian Mirela , Brad Laura , Zaharia Alina
Published: August 2022

The interactions between nature and humankind produce a series of ecological, social, economic, institutional, technological, and other types of restrictions, which can alter the development of the future society and Earth. Exploring the influencing factors of environmental performance can create better solutions and it can emphasize the gaps from past and current policies. Also, they can contribute to achieve sustainable development. In this regard, more indices are developing for assessing a specific theme that targets sustainability, such as carbon footprint, Environmental Performance Index, or sustainable development index. Thus, this study aims to analyze the influencing factors of Environmental Performance Index (EPI) at an EU level by collecting data between 2010 and 2020, once in 2 years and by using a panel data model. The results were estimated using the Period SUR effect within the generalized least square method and using the White period matrix within the correlation matrix. The results indicate positive relationships between EPI and area under organic farming, circular material use rate, eco-innovation index, energy productivity, ratio of female-to-male labor force participation rate, forest area, Human Development Index, Internet users, livestock production index, new business density, patent applications-residents, tertiary school enrollment, the share of renewable energy consumption in gross final energy consumption, and the proportion of seats held by women in national parliaments. In addition, higher inequality between individuals, natural resources rents, trade volume index, and environmental taxes in total tax revenues seem to constrain the EU’s environmental performance. The results are important both for academicians and policymakers.
Environmental Regulation and Corporate Innovation Behavior Based on the “Double Carbon” Strategy – Empirical Analysis Based on A-Share Listed Companies of Heavy Pollution Industries on the Shanghai and Shenzhen Stock Exchanges
Authors: Ying Nie , Yao Li , Jihong Xin , Daqing Wang
Published: August 2022

Environmental regulations have been intensified across the country under the pressure of the national “double carbon” strategy, the constraints of energy-saving and emission-reduction targets by enterprises, and public opinion. The tightening of environmental regulations is bound to impact the innovation behavior of heavily polluting enterprises; however, it remains uncertain whether the impact is positive or negative. Using a differences-in-differences approach of data from listed companies in China’s heavily-polluting industries between 2010 and 2016, this paper examines the changes in their innovation behavior under the tightening environmental regulations after the “smog explosion” event as a “quasi-natural experiment” at the end of 2011. The study found that the “smog event” had a significant net negative effect on the innovation behavior of heavily polluting firms, with a significant decrease in their innovation inputs. The quantile regression results show that the R&D intensity of enterprises is related to the haze treatment effect in a U-shaped curve. Further research found that the decline in innovation investment was more significant for state-owned heavily-polluting firms compared to private heavy polluting firms. Robustness tests indicate that the empirical results of this paper are somewhat robust. This paper aims to identify the contradictory roots of the “Porter hypothesis” debate by analyzing the differences in innovation behavior of enterprises with different R&D intensity and different property rights.
Recent Advances in Sugarcane Genomics, Physiology, and Phenomics for Superior Agronomic Traits
Authors: Meena Mintu Ram , Appunu Chinnaswamy , Arun Kumar R. , Manimekalai R. , Vasantha S. , Krishnappa Gopalareddy , Kumar Ravinder , Pandey S. K. , Hemaprabha G.
Published: August 2022

Advances in sugarcane breeding have contributed significantly to improvements in agronomic traits and crop yield. However, the growing global demand for sugar and biofuel in the context of climate change requires further improvements in cane and sugar yields. Attempts to achieve the desired rates of genetic gain in sugarcane by conventional breeding means are difficult as many agronomic traits are genetically complex and polygenic, with each gene exerting small effects. Unlike those of many other crops, the sugarcane genome is highly heterozygous due to its autopolyploid nature, which further hinders the development of a comprehensive genetic map. Despite these limitations, many superior agronomic traits/genes for higher cane yield, sugar production, and disease/pest resistance have been identified through the mapping of quantitative trait loci, genome-wide association studies, and transcriptome approaches. Improvements in traits controlled by one or two loci are relatively easy to achieve; however, this is not the case for traits governed by many genes. Many desirable phenotypic traits are controlled by quantitative trait nucleotides (QTNs) with small and variable effects. Assembling these desired QTNs by conventional breeding methods is time consuming and inefficient due to genetic drift. However, recent developments in genomics selection (GS) have allowed sugarcane researchers to select and accumulate desirable alleles imparting superior traits as GS is based on genomic estimated breeding values, which substantially increases the selection efficiency and genetic gain in sugarcane breeding programs. Next-generation sequencing techniques coupled with genome-editing technologies have provided new vistas in harnessing the sugarcane genome to look for desirable agronomic traits such as erect canopy, leaf angle, prolonged greening, high biomass, deep root system, and the non-flowering nature of the crop. Many desirable cane-yielding traits, such as single cane weight, numbers of tillers, numbers of millable canes, as well as cane quality traits, such as sucrose and sugar yield, have been explored using these recent biotechnological tools. This review will focus on the recent advances in sugarcane genomics related to genetic gain and the identification of favorable alleles for superior agronomic traits for further utilization in sugarcane breeding programs.
Regulation of the Signal-Dependent E Protein HEBAlt Through a YYY Motif Is Required for Progression Through T Cell Development
Authors: Yoganathan Kogulan , Yan Anqi , Rocha Juliana , Trotman-Grant Ashton , Mohtashami Mahmood , Wells Lisa , Zúñiga-Pflücker Juan Carlos , Anderson Michele K.
Published: August 2022

The E protein transcription factors E2A and HEB are critical for many developmental processes, including T cell development. We have shown that theTcf12locus gives rise to two distinct HEB proteins, with alternative (HEBAlt) and canonical (HEBCan) N-terminal domains, which are co-expressed during early T cell development. While the functional domains of HEBCan have been well studied, the nature of the HEBAlt-specific (Alt) domain has been obscure. Here we provide compelling evidence that the Alt domain provides a site for the molecular integration of cytokine signaling and E protein activity. Our results indicate that phosphorylation of a unique YYY motif in the Alt domain increases HEBAlt activity by 10-fold, and that this increase is dependent on Janus kinase activity. To enablein vivostudies of HEBAlt in the T cell context, we generated ALT-Tg mice, which can be induced to express a HA-tagged HEBAlt coding cassette in the presence of Cre recombinases. Analysis of ALT-Tg mice on the Vav-iCre background revealed a minor change in the ratio of ISP cells to CD8+ SP cells, and a mild shift in the ratio of T cells to B cells in the spleen, but otherwise the thymus, spleen, and bone marrow lymphocyte subsets were comparable at steady state. However, kinetic analysis of T cell development in OP9-DL4 co-cultures revealed a delay in early T cell development and a partial block at the DN to DP transition when HEBAlt levels or activity were increased. We also observed that HEBCan and HEBAlt displayed significant differences in protein stability that were resolved in the thymocyte context. Finally, a proteomic screen identified STAT1 and Xpo1 as potential members of HEBAlt-containing complexes in thymocytes, consistent with JAK-induced activation of HEBAlt accompanied by translocation to the nucleus. Thus, our results show that the Alt domain confers access to multiple layers of post-translational control to HEBAlt that are not available to HEBCan, and thus may serve as a rheostat to tune E protein activity levels as cells move through different thymic signaling environments during T cell development.
Microneedling combined with compound betamethasone in treatment of severe alopecia areata: A case report
Authors: Pei Danning , Chen Lirong , Yao Yue , Zeng Linxi , Zhang Guoqiang
Published: August 2022

Alopecia areata (AA) is a common inflammatory, non-cicatricial hair loss. At present, it is considered that its pathogenesis is an autoimmune disease specific to hair follicle organs mediated by T cells under the combined action of genetic and environmental factors. Treatment is challenging for children with severe AA who are resistant or intolerant to conventional treatment.Here, we treated a 3-year-old child with severe AA with microneedling combined with compound betamethasone. After 6 months of treatment, the patient’s condition was significantly improved, and most of the primary hair loss areas had hair regeneration.
Case report: Safety and efficacy of adalimumab in treating difficult-to-treat rheumatoid arthritis in a human immunodeficiency virus-positive patient, one year follow-up
Authors: Chen Jing-Wen , Deng Guo-Shu , Zhang Wen-Shuang , Zhang Ming-Ying , Guan Tong , Xu Qiang
Published: August 2022

Rheumatoid arthritis (RA) is a joint-disabling inflammatory disease associated with the pathology of synovitis. Some patients with RA are difficult to treat, using disease-modifying anti-rheumatic drugs (DMARDs). Biology and targeted synthetic DMARDs (b/tsDMARDs) are options for patients with RA. Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). Adalimumab is an anti-tumor necrosis factor therapy commonly used in patients with RA. However, there are no reports or related data on patients with RA-HIV/AIDS treated with adalimumab are available. In this report, we described the first successful case of a 60-year-old HIV-positive woman with difficult-to-treat RA treated with ADA after being screened for hepatitis virus, latent tuberculosis (LTBI), and other infections. She contracted HIV from sexual exposure while on adalimumab therapy. As the patient was resistant to first-line DMARDs, she continued adalimumab along with the initiation of highly active antiretroviral therapy (HAART). The patient was treated with adalimumab therapy for a year; her CD4+ lymphocyte count was normal, HIV-1 RNA decreased, and no new infections were triggered. The patient achieved clinical remission of RA. In conclusion, adalimumab is a safe option for patients with RA-HIV and may slow the progression of HIV infection. Furthermore, HAART has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.

Conclusions

Adalimumab is a safe option for patients with RA-HIV, and may slow down the progression of HIV infection. The HAART therapy has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.
Spatial localization of cathepsins: Implications in immune activation and resolution during infections
Authors: Anes Elsa , Pires David , Mandal Manoj , Azevedo-Pereira José Miguel
Published: August 2022

Cathepsins were first described, as endolysosomal proteolytic enzymes in reference to the organelles where they degrade the bulk of endogenous and exogenous substrates in a slightly acidic environment. These substrates include pathogens internalizedviaendocytosis and/or marked for destruction by autophagy. However, the role of cathepsins during infection far exceeds that of direct digestion of the pathogen. Cathepsins have been extensively investigated in the context of tumour associated immune cells and chronic inflammation. Several cathepsin-dependent immune responses develop in the endocytic pathway while others take place in the cytosol, the nucleus, or in the extracellular space. In this review we highlight the spatial localization of cathepsins and their implications in immune activation and resolution pathways during infection.
Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
Authors: Jin Wenxv , Chen Xiong , Kong Lingguo , Huang Chongqing
Published: August 2022

Wound healing is impaired in the diabetic status, largely attributable to diabetes-associated angiopathy. Pericytes play critical roles in the stabilization of the formed vessels. The loss and dysfunction of pericytes have been reported in inflammation during diabetes and associated with the pathology of diabetic angiopathy. However, a practical approach that targets inflammatory pericytes to improve diabetic wound healing is lacking. In the current study, we showed that the inflammatory pericytes from wound skin of diabetic patients were impaired in growth potential and underwent oxidative stress and apoptosis. Expression of antioxidant gene oxidation resistance protein 1 (OXR1) specifically in pericytes through an adenovirus carrying OXR1 under a pericyte-specific neuron glia antigen-2 (NG2) promoter (AV-NG2p-OXR1) relieved the oxidative stress, reduced the apoptosis, and recovered the growth potential in diabetic pericytes. Moreover, expression of OXR1 in diabetic pericytes retrieved their potential of both suppressing the migration of co-cultured HUVECs and inducing cell aggregates at the branching points, indicating a functional recovery. In vivo gene therapy using this AV-NG2p-OXR1 to DB/DB mice, the mouse model for type 2 diabetes, significantly improved wound healing, likely through enhancing blood flow at the wound rather than increasing vessel density. Together, our data suggest that gene therapy targeting inflammatory pericytes may improve diabetes-associated impaired wound healing.
Research advance in the taxonomy and ecology of Oncaeidae Giesbrecht, 1893
Authors: Sun Rouxin , Wang Yanguo , Wang Chunguang , Xiang Peng , Chen Xiaoyin , Xing Bingpeng
Published: August 2022

The Oncaeidae is an important family of small copepods in marine ecosystems and is characterized by high diversity and abundance. The family was established by Giesbrecht in the late 19th century. Since then, 115 oncaeid species have been discovered and described. However, Oncaeidae species are small-sized and show considerable morphological similarity. The family includes a great number of sibling species and intraspecific form variants. Consequently, there are large knowledge gaps regarding their taxonomy and diversity, and their importance in marine ecosystems may have been underestimated. In this study, we have charted the progress of oncaeid taxonomy and diversity studies worldwide. We have identified the major challenges faced by the researchers and have described the marine science techniques. We also provide an overview of the distribution and ecology of the family Oncaeidae. Progress has been made toward understanding the distribution, habitat preference, and feeding behavior of oncaeids. The knowledge of oncaeids taxonomy has also been considerably increased by improvements in the research methodology, such as the use of molecular biology techniques and interdisciplinary approaches in tandem with the traditional taxonomic methods.
Comparative transcriptome analysis of the differentiating gonads in Scatophagus argus
Authors: Mustapha Umar Farouk , Peng You-Xing , Huang Yuan-Qing , Assan Daniel , Zhi Fei , Shi Gang , Huang Yang , Li Guang-Li , Jiang Dong-Neng
Published: August 2022

The reproductive-related studies, including genetic and genomic such as gonadal transcriptome analyses, have previously focused on the adult spotted scat, with little information on juvenile fish. Transcriptomics is a powerful tool that allows for massive parallel analysis to identify differential expression and the patterns of gene expression holistically at a particular stage in a cell or tissue development. This study presents the first report on gonadal transcriptome analysis of the differentiating (juvenile; 4 months after hatch; stage I ovary and testis) spotted scat gonads. The study revealed potential reproduction and gonadal development-related genes. A total of 25936 genes were identified, of which 16248 were co-expressed, 17893 and 17258 expressed in males and females, respectively, from sequence data of testis I (n = 3) and ovary I (n = 2). A total of 6549 differentially expressed genes (DEGs) were identified between males and females. Genes attributable to male gonad development pathway such as dmrt1, gsdf, and amh are significantly expressed in differentiating testes, while female-related genes such as foxl2, cyp19a1a, 42sp50 and sox3 were expressed considerably in differentiating ovaries. In addition, dmrt1/dmrt1y was not expressed in the female (FPKM=0.00), while its paralog dmrt1b was expressed in both males and females. In the male pathway, dmrt1y and gsdf are critical for sex determination and maintenance while foxl2/foxl3 and cyp19a1a are critical in the female development pathway. The current studies provide an insight into the expression patterns of sex and gonadal-related genes in differentiating gonads of spotted scat.
Injectable hyaluronic acid/oxidized chitosan hydrogels with hypochlorous acid released for instant disinfection and antibacterial effects
Authors: Chen Han , Liao Ran , Du Qianqian , Li Cong , Xiao Xiufeng , Shan Yongqi
Published: August 2022

Bacterial infections of wounds significantly increase the occurrence of complications, which have become a public health problem and pose a serious threat to human health. Therefore, an ideal wound dressing should not only possess suitable mechanical strength and a moist environment, but also instant disinfection and antibacterial properties. Owing to their high water content and permeability, hydrogels have great potential for the application in wound dressing. In this study, we developed an injectable hyaluronic acid (HA)/oxidized chitosan (OCS) hydrogel with good biocompatibility, self-healing, and tissue adhesive properties. Moreover, the slow release of micro hypochlorous acid (HClO), which is a common bactericide during hydrogel formation, can lead to instant disinfection; and the positive charge of OCS in this hydrogel can achieve a sustainable antibacterial effect. Thus, this hydrogel is a promising wound dressing material in clinical treatments.
Effectiveness and safety of morinidazole in the treatment of pelvic inflammatory disease: A multicenter, prospective, open-label phase IV trial
Authors: Zhou Ting , Yuan Ming , Cui Pengfei , Li Jingjing , Jia Feifei , Wang Shixuan , Liu Ronghua
Published: August 2022

Background

Antimicrobial resistance to metronidazole has emerged after several decades of worldwide use of the drug. The purpose of this study was to evaluate the effectiveness, safety and population pharmacokinetics of morinidazole plus levofloxacin in adult women with pelvic inflammatory disease (PID).

Methods

Patients in 30 hospitals received a 14-day course of 500 mg intravenous morinidazole twice daily plus 500 mg of levofloxacin daily. A total of 474 patients were included in the safety analysis set (SS); 398 patients were included in the full analysis set (FAS); 377 patients were included in the per protocol set (PPS); 16 patients were included in the microbiologically valid (MBV) population.

Results

The clinical resolution rates in the FAS and PPS populations at the test of cure (TOC, primary effectiveness end point, 7–30 days post-therapy) visit were 81.91 and 82.49% (311/377), respectively. There were 332 patients who did not receive antibiotics before treatment, and the clinical cure rate was 82.83%. Among 66 patients who received antibiotics before treatment, 51 patients were clinically cured 7–30 days after treatment, with a clinical cure rate of 77.27%. The bacteriological success rate in the MBV population at the TOC visit was 87.5%. The minimum inhibitory concentration (MIC) values of morinidazole for use against these anaerobes ranged from 1 to 8 μg/mL. The rate of drug-related adverse events (AEs) was 27.43%, and no serious AEs or deaths occurred during the study.

Conclusions

The study showed that treatment with a 14-day course of intravenous morinidazole, 500 mg twice daily, plus levofloxacin 500 mg daily, was effective and safe. The results of this study were consistent with the results of a phase III clinical trial, which verified the effectiveness and safety of morinidazole.
Neutralizing monoclonal antibodies against SARS-CoV-2 for COVID-19 pneumonia in a rituximab treated patient with systemic sclerosis—A case report and literature review
Authors: Yalcin Mutlu Melek , Taubmann Jule , Wacker Jochen , Tascilar Koray , Fagni Filippo , Gerner Maximilian , Klett Daniel , Schett Georg , Manger Bernhard , Simon David
Published: August 2022

Patients with immune-mediated diseases (IMID) such as systemic sclerosis (SSc), who are treated with B cell depleting treatments, are at risk for developing severe COVID-19 due to inadequate humoral immune response. During B cell depletion, therapeutic substitution of neutralizing monoclonal antibodies against the SARS-CoV-2 spike protein (mAbs) might be helpful to prevent severe COVID-19. It has been shown, that in non-IMID patients mABs reduce SARS-CoV-2 viral load and lower the risk of COVID-19 associated hospitalization or death. However, there are limited data on the effect of mAbs in IMID patients after exposure, especially in patients treated with B cell depleting agents. Herein, we report a case of a rituximab treated SSc patient who developed COVID-19 and was successfully treated with a combination of mAbs (casirivimab/imdevimab). With this case we show that IMID patients may benefit from post-exposure administration of mAbs. In our case treatment with neutralizing autoantibodies was safe and a possible contributor in protecting the patient from mechanical ventilation and eventually death. We frame this case within the current evidence from the literature and provide a perspective on the future potential role of mAbs for treating IMID patients suffering from COVID-19.
Overactivation of the complement system may be involved in intrarenal arteriolar lesions in IgA nephropathy
Authors: Guo Wei-yi , An Xiu-ping , Sun Li-jun , Dong Hong-rui , Cheng Wen-rong , Ye Nan , Wang Guo-qin , Xu Xiao-yi , Zhao Zhi-rui , Cheng Hong
Published: August 2022

Introduction

IgA nephropathy (IgAN) encompasses a wide range of clinical and histology features. Some patients present without hematuria, with or without hypertension, still rapidly progress in renal function. Renal pathology of this part of patients were predominant intrarenal arteriolar lesions, rarely presented glomerular proliferative lesions. We aim to investigate the clinical and pathological characteristics and prognosis of these IgAN patients and initially explore whether the abnormal activation of complement is involved in the intrarenal arteriolar lesions of IgAN.

Methods

A total of 866 patients with renal biopsy-proven IgAN diagnosed at Beijing Anzhen Hospital were recruited. IgAN patients without intrarenal arteriolar lesions and proliferative lesions were excluded (n = 115), the rest were divided into arteriolar lesions group (n = 202) and proliferative lesions group (n = 549). Among them, 255 patients were regularly followed up for at least 1 year. Renal biopsy tissues of 104 IgAN patients were stained for complement components by immunohistochemistry and immunofluorescence.

Results

Compared with proliferative lesions group, the arteriolar lesions group experienced high percentage of hypertension (p = 0.004), low percentage of gross hematuria (p = 0.001), microscopic hematuria (p < 0.001) and less initial proteinuria (p = 0.033). Renal survival between the two groups was not significantly different (p = 0.133). MBL, C4d, FH and FHR5, C3c, and MAC deposited on intrarenal arteriole in arteriolar lesions group. Compare with the proliferative lesion group, the arteriolar lesions group exhibited a higher intensity of C3c deposition on the intrarenal arterioles (p = 0.048). C3c and CD31 co-deposited on intrarenal arterioles area in patients with intrarenal arteriolar lesions.

Conclusion

Renal survival of the IgAN patients in arteriolar lesions group was not better than those in proliferative lesions group. Abnormal activation of complement may be involved in the pathogenesis of arteriolar damage through the injury of endothelial cells in this clinical phenotype of IgAN.
Naringenin restores colistin activation against colistin-resistant gram-negative bacteria in vitro and in vivo
Authors: Xu Mengxin , Yao Zhuocheng , Zhao Yining , Shi Shiyi , Sun Yao , Feng Luozhu , Zhou Cui , Zhang Xiaodong , Cao Jianming , Zhou Tieli
Published: August 2022

Colistin is used as the “last line of defense” against multidrug-resistant (MDR) Gram-negative bacteria (GNB). However, improper use of colistin may further lead to an increasing number of colistin-resistant (Col-R) strains worldwide, which greatly limits antibiotic treatment options. In this study, we investigated the antibacterial and antibiofilm activities of naringenin (NG) combined with colistin against Col-R GNB in vitro and in vivo. The checkerboard method and time-kill test showed that NG combined with colistin has better antibacterial activity (FICI < 0.5) compared with NG and colistin alone. Biofilm formation inhibition tests demonstrated that combining the two drugs could inhibit biofilm formation; scanning electron microscopy (SEM) confirmed that the combination of the two significantly reduces the number of cells in the biofilm compared with the drug alone. The in vivo experiment showed that the combination of NG and colistin can improve the survival rate of the Galleria mellonella (G. mellonella) and reduce the microbial load in the mouse thigh infection model. Mechanistically, the combination of NG and colistin synergistically enhances the antibacterial activity and changes the permeability of the bacterial outer membrane. More importantly, cytotoxicity tests showed no cell cytotoxicity of NG in combination with colistin. In conclusion, our data revealed that NG combined with colistin exhibited good synergistic effects in vivo and in vitro, thus providing a new therapeutic option for clinical Col-R GNB infections.
The attenuated Mycoplasma bovis strain promotes apoptosis of bovine macrophages by upregulation of CHOP expression
Authors: Zhang Hui , Lu Siyi , Chao Jin , Lu Doukun , Zhao Gang , Chen Yingyu , Chen Huanchun , Faisal Muhammad , Yang Liguo , Hu Changmin , Guo Aizhen
Published: August 2022

Mycoplasma bovis (M. bovis) is one of the major pathogens in the bovine respiratory disease complex, which includes pneumonia, mastitis, and arthritis and causes a great economic loss in the cattle industry. In China, a live-attenuated vaccine strain M. bovis P150 was obtained by a continuous culture of the wild-type strain M. bovis HB0801 (P1) in vitro for 150 passages. Using the infected bovine macrophage cell line BoMac, this work attempted to investigate the mechanism of P150 attenuation and protective immune response. To begin, we show that M. bovis P150 effectively triggered cytotoxicity and apoptosis in BoMac, although with lower intracellular survival than P1. The transcriptomes of BoMac after infection with M. bovis strains P1 and P150 were sequenced, and bioinformatic analysis identified 233 differentially expressed genes (DEGs), with 185 upregulated and 48 downregulated. Further Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses revealed that the majority of the DEGs were linked to CHOP complex, MAP kinase phosphatase activity and were involved in the IL-17 signaling pathway in immune response, MAPK signaling pathway in signal transduction, and p53 signaling pathway in cell growth and death. Among them, the level of C/EBP homologous protein (CHOP) was significantly upregulated in P150-infected BoMac compared to P1-infected cells at different time points, along with its upstream and downstream genes phosphorylated-PERK, phosphorylated-EIF2α, ATF4, and GADD45A increased in the PERK-dependent ER stress response. The role of CHOP in apoptosis was further verified by M. bovis-induced siCHOP knockdown in BoMac cells. The results showed that CHOP knockdown enhanced P150-induced apoptosis and dramatically increased the M. bovis P1 and P150 intracellular survival, particularly for P150. These data suggest that P150 infection upregulates CHOP expression, which can increase apoptosis and mediate a crosstalk between ER stress and apoptosis during infection, and hence, contribute to high cytotoxicity and low intracellular survival.
Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027
Authors: Li Xingxing , Ren Weicong , Li Yihong , Shi Yuanyuan , Sun Hongmin , Wang Lifei , Wu Linzhuan , Xie Yunying , Du Yu , Jiang Zhibo , Hong Bin
Published: August 2022

Natural products from microorganisms are important sources for drug discovery. With the development of high-throughput sequencing technology and bioinformatics, a large amount of uncharacterized biosynthetic gene clusters (BGCs) in microorganisms have been found, which show the potential for novel natural product production. Nine BGCs containing PKS and/or NRPS in Streptomyces globisporus C-1027 were transcriptionally low/silent under the experimental fermentation conditions, and the products of these clusters are unknown. Thus, we tried to activate these BGCs to explore cryptic products of this strain. We constructed the cluster-situated regulator overexpressing strains which contained regulator gene(s) under the control of the constitutive promoter ermE*p in S. globisporus C-1027. Overexpression of regulators in cluster 26 resulted in significant transcriptional upregulation of biosynthetic genes. With the separation and identification of products from the overexpressing strain OELuxR1R2, three ortho-methyl phenyl alkenoic acids (compounds 1–3) were obtained. Gene disruption showed that compounds 1 and 2 were completely abolished in the mutant GlaEKO, but were hardly affected by deletion of the genes orf3 or echA in cluster 26. The type II PKS biosynthetic pathway of chain-extended cinnamoyl compounds was deduced by bioinformatics analysis. This study showed that overexpression of the two adjacent cluster-situated LuxR regulator(s) is an effective strategy to connect the orphan BGC to its products.
The oxygen dilemma: The challenge of the anode reaction for microbial electrosynthesis from CO2
Authors: Abdollahi Maliheh , Al Sbei Sara , Rosenbaum Miriam A. , Harnisch Falk
Published: August 2022

Microbial electrosynthesis (MES) from CO2 provides chemicals and fuels by driving the metabolism of microorganisms with electrons from cathodes in bioelectrochemical systems. These microorganisms are usually strictly anaerobic. At the same time, the anode reaction of bioelectrochemical systems is almost exclusively water splitting through the oxygen evolution reaction (OER). This creates a dilemma for MES development and engineering. Oxygen penetration to the cathode has to be excluded to avoid toxicity and efficiency losses while assuring low resistance. We show that this dilemma derives a strong need to identify novel reactor designs when using the OER as an anode reaction or to fully replace OER with alternative oxidation reactions.
Changes in phosphorus mobilization and community assembly of bacterial and fungal communities in rice rhizosphere under phosphate deficiency
Authors: Sun Ruibo , Zhang Wenjie , Liu Yangbing , Yun Wenjing , Luo Bingbing , Chai Rushan , Zhang Chaochun , Xiang Xingjia , Su Xiaofeng
Published: August 2022

Rhizosphere microorganisms are closely associated with phosphorus (P) uptake in plants and are considered potential agents to mitigate P shortage. However, the mechanisms of rhizospheric microbial community assembly under P deficiency have yet to be elucidated. In this study, bacterial and fungal communities in rice rhizosphere and their P mobilization potential under high (+P) and low (−P) concentrations of P were investigated. Bacterial and fungal community structures were significantly different between −P and +P treatments. And both bacterial and fungal P-mobilizing taxa were enriched in-P treatment; however, the proportion of P-mobilizing agents in the fungal community was markedly greater than that in the bacterial community. A culture experiment confirmed that microbial phosphate solubilizing capacity was significantly higher in −P treatment compared with that in +P treatment. −P treatment lowered bacterial diversity in rice rhizosphere but increased fungal diversity. Further analysis demonstrated that the contribution of deterministic processes in governing bacterial community assembly was strengthened under P deficiency but was largely weakened in shaping the fungal community. These results highlighted that enriching P-mobilizing microbes in the rhizosphere is a vital way for rice to cope with P deficiency, and that fungi contribute considerably to P mobilization in rice rhizosphere. Findings from the study provide novel insights into the assembly of the rhizosphere microbiome under P deficiency and this will facilitate the development of rhizosphere microbial regulation strategies to increase nutrient uptake in plants.
Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
Authors: García-Crespo Carlos , Vázquez-Sirvent Lucía , Somovilla Pilar , Soria María Eugenia , Gallego Isabel , de Ávila Ana Isabel , Martínez-González Brenda , Durán-Pastor Antoni , Domingo Esteban , Perales Celia
Published: August 2022

We report a quantification of the decrease of effectiveness of antiviral agents directed to hepatitis C virus, when the agents are added during an ongoing infection in cell culture vs. when they are added at the beginning of the infection. Major determinants of the decrease of inhibitory activity are the time post-infection of inhibitor administration and viral replicative fitness. The efficacy decrease has been documented with antiviral assays involving the combination of the direct-acting antiviral agents, daclatasvir and sofosbuvir, and with the combination of the lethal mutagens, favipiravir and ribavirin. The results suggest that strict antiviral effectiveness assays in preclinical trials may involve the use of high fitness viral populations and the delayed administration of the agents, relative to infection onset.