bluuebunny/crossref_metadata_2025 huggingface dataset:
Tipping point: The staff wellbeing crisis in higher education
Authors: Jayman Michelle , Glazzard Jonathan , Rose Anthea
Published: August 2022

This marketised higher education environment in the UK has had dire consequences for academics at all levels. Literature suggests that academics are busier and working faster than ever. There is evidence of an undermining of academic professionalism, academic freedom and increased job insecurity in the sector. It is not possible for academics to position themselves outside of the performance culture and still be viewed as a valued team member. Within this paper, our concerns relate specifically to the impact of this culture of performativity on the wellbeing of staff who work in UK higher education institutions.
OPN inhibits autophagy through CD44, integrin and the MAPK pathway in osteoarthritic chondrocytes
Authors: Bai Rui-Jun , Liu Di , Li Yu-Sheng , Tian Jian , Yu Deng-Jie , Li Heng-Zhen , Zhang Fang-Jie
Published: August 2022

Background

To investigate whether osteopontin (OPN) affects autophagy in human osteoarthritic chondrocytes and determine the roles of CD44, αvβ3 integrin and the Mitogen-activated protein kinase (MAPK) pathway in this progress.

Methods

First, we compared the autophagy levels in the human osteoarthritis (OA) and normal cartilage, then, we cultured human OA chondrocytes in vitro and treated cells with recombinant human OPN (rhOPN) to determine autophagy changes. Next, the anti-CD44 and anti-CD51/61 monoclonal antibodies (Abs) or isotype IgG were used to determine the possible role of CD44 and αvβ3 integrin; subsequently, an inhibitor of the ERK MAPK pathway was used to investigate the role of ERK MAPK. Western blotting was used to measure the Beclin1, LC3 II and MAPK proteins expressions, mRFP-GFP-LC3 confocal imaging and transmission electron microscopy were also used to detect the autophagy levels. Cell Counting Kit-8 (CCK-8) was used to assay the proliferation and activity of chondrocytes.

Results

The LC3 protein was greatly decreased in OA cartilage compared to normal cartilage, and OPN suppressed the autophagy activity in chondrocytes in vitro. Blocking experiments with anti-CD44 and anti-CD51/61 Abs indicated that OPN could suppress the expression of LC3II and Beclin1 through αvβ3 integrin and CD44. Our results also indicated that the ratio of p-ERK/ERK but not p-P38/P38 and p-JNK/JNK was increased after the rhOPN treatment. The ERK inhibitor inhibited the activity of OPN in the suppression of autophagy, and the CCK-8 results showed that rhOPN could promote chondrocyte proliferation.

Conclusion

OPN inhibited chondrocyte autophagy through CD44 and αvβ3 integrin receptors and via the ERK MAPK signaling pathway.
The value of ultrasound grayscale ratio in the diagnosis of papillary thyroid microcarcinomas and benign micronodules in patients with Hashimoto’s thyroiditis: A two-center controlled study
Authors: Feng Na , Wei Peiying , Kong Xiangkai , Xu Jingjing , Yao Jincao , Cheng Fang , Ou Di , Wang Liping , Xu Dong , Han Zhijiang
Published: August 2022

Objective

The value of ultrasound grayscale ratio (UGSR) in the diagnosis of papillary thyroid microcarcinomas (PTMCs) and benign micronodules (BMNs) has been recognized by some authors, but studies have not examined these aspects in patients with Hashimoto’s thyroiditis (HT). This retrospective study investigated the value of UGSR in the diagnosis of PTMCs and BMNs in patients with HT using data from two medical centers.

Methods

Ultrasound images of 428 PTMCs in 368 patients with HT and 225 BMNs in 181 patients with HT in center A were retrospectively analyzed and compared to the ultrasound images of 412 PTMCs in 324 patients with HT and 315 BMNs in 229 patients with HT in medical center B. All of the cases were surgically confirmed. The UGSR was calculated as the ratio of the grayscale value of lesions to the surrounding normal thyroid tissues. The optimal UGSR thresholds for the PTMCs and BMNs in patients with HT from the two medical centers were determined using a receiver operating characteristic (ROC) curve. Furthermore, other statistics, including the area under the curve (AUC), the optimal UGSR threshold, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the two medical centers, were pair analyzed in this study.

Results

The UGSR of PTMCs and BMNs in patients with HT from medical center A were 0.513 (0.442, 0.592) and 0.857 (0.677, 0.977) (Z = −15.564, p = 0), and those from medical center B were 0.514 (0.431, 0.625) and 0.917 (0.705, 1.131) (Z = −15.564, p = 0). For both medical centers A and B, the AUC, optimal UGSR threshold, sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the UGSR in differentiating between PTMCs and BMNs in patients with HT were 0.870 and 0.889, 0.68 and 0.70, 0.921 and 0.898, 0.747 and 0.759, 0.874 and 0.829, 0.832 and 0.848, and 0.861 and 0.836, respectively. There were no significant differences in the UGSR for the PTMCs between patients from the two medical centers (Z = −0.815, p = 0.415), while there was a significant difference in the UGSR of the BMNs between patients from the two medical centers (Z = −3.637, p = 0).

Conclusion

In the context of HT, UGSR still has high sensitivity, accuracy, and stability in differentiating between PTMCs and BMNs, making it a complementary differentiator of thyroid imaging reporting and data systems. However, due to its low specificity, a comprehensive analysis of other ultrasound signs is required.
A Dynamic Evaluation Method for High-Permeability New Energy Distribution Network Planning Considering Multistage Development Trends
Authors: Zhang Junxiao , Gao Chong , Wang Tianlin , Duan Yao , Xu Min , Guo Zuogang
Published: August 2022

With the development of new power systems, high penetration of new energy (HPNE) will become a major feature of power systems in the future. In order to solve the problem that the traditional distribution network planning index makes it difficult to fully consider the impact of new energy access on the distribution network, this paper constructs a distribution network planning evaluation index system considering the characteristics of HPNE, and designs a set of static comprehensive evaluation methods of distribution network planning schemes based on the “over-average penalty” entropy weight method (EWM). At the same time, distribution network planning is a long-term dynamic process, and the static evaluation method makes it difficult to describe the actual situation of the multistage construction process of distribution networks. To this end, a dynamic evaluation method of distribution network planning is proposed, which realizes the comprehensive evaluation of multistage distribution network planning based on dual excitation control lines. Finally, an example of four 10 kV distribution network planning schemes of a power supply bureau are analyzed to prove the effectiveness of the proposed method.
Study on Waste Acid Modificated Industrial Solid Waste Aluminum Ash to Prepare Environmental Functional Materials to Remove Fluoride Ions in Wastewater
Authors: Ren Yuanchuan , Chen Xiuping , Qu Guangfei , Wu Fenghui , Yang Yuyi , Wang Zuoliang , Liu Xinxin , Jin Caiyue , Hu Yan
Published: August 2022

C-SAAoa particles synthesized by simple and low-cost calcining industrial solid waste aluminium ash combined with waste oxalic acid modification process show excellent performance in fluoride removal speed and adsorption capacity. Their adsorption capacity on fluoride was determined at about 180.57 mg/g at pH 3.0, which was among the highest reported values in the literature. It was determined that the adsorption mechanism of fluoride on C-SAAoa particles followed mechanisms such as ion exchange, electrostatic action, and the surface - OH groups played a major role in the fluoride removal process. C-SAAoa particles can effectively remove fluoride, even in the presence of a certain concentration of competing anions. At the same time, the material possesses good cycling performance, and can still maintain 78.9% of the initial adsorption capacity in the longitudinal for eight recycles. Therefore, it may have the potential to become a promising adsorbent as a supplement to industrial solid waste resource-based utilization processes and also for fluoride removal in small-scale treatment facilities or wastewater with high fluoride concentrations.
In situ, high-resolution evidence of metals at the sediment-water interface under ice cover in a seasonal freezing lake
Authors: Yuan Yuxiang , Wang Qichen , Dong Xiangqian , Zhu Yinze , Wu Zhong , Yang Qian , Zuo Yunjiang , Liang Shuang , Wang Chunqing , Zhu Xiaoyan
Published: August 2022

The ice cover in winter as a physical barrier and duration would profoundly impact on changes in endogenous metal loading, migration, and transformation. Although a gradual reduction in duration and occurrence of lake ice cover in boreal lake ecosystems has been confirmed, little attention to the ice-covered period is received compared to open water studies. In this study, novel-developed diffusive gradients in thin films (DGT, ZrO-Chelex) probes were deployed to obtain the in-situ and high-resolution information on metals (Cu, Zn, Pb, Mn, Cd, Cr, and As) at the sediment-water interface (SWI) in a seasonal ice-covered lake, Chagan Lake. In addition, “source-sink” characteristics of each metal related to their endogenous release were determined based on Fick’s first law. Concentrations of labile metals at the SWI demonstrated significant spatial heterogeneity, peaking exactly below the SWI. Compared with other similar studies, concentrations of Pb (0.55 μg/L), Cr (0.58 μg/L), and As (2.4 μg/L) were a little higher even under-ice than that in other freshwater rivers and lakes, indicating potential pollution due to the agricultural intensification and petroleum extraction. The apparent diffusive fluxes suggested that sediments acted as a sink for Pb (−0.01 mg m–2 day–1), Cr (−2.37 mg m–2 day–1), and Cd (−0.1 mg m–2 day–1), diffusing from the overlying water into the sediment, while Cu (0.12 mg m–2 day–1), Zn (0.75 mg m–2 day–1), Mn (15.89 mg m–2 day–1), and As (2.12 mg m–2 day–1) as a source from sediments into the overlying water. Dissolved oxygen was the principal factor (79.5%, P = 0.032), determining the variation of the available metals at the SWI. As the urgent need for research focused on under-ice ecosystem dynamics, this study addressed the previously unknown behavior of the labile metals at the SWI and provided a unique perspective for the lake management during the ice-cover periods when external nutrient input was cut off.
Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue
Authors: Lamkin Donald M. , Chen Shiuan , Bradshaw Karen P. , Xu Shili , Faull Kym F. , Sloan Erica K. , Cole Steve W.
Published: August 2022

The low-dose mixture hypothesis of carcinogenesis proposes that exposure to an environmental chemical that is not individually oncogenic may nonetheless be capable of enabling carcinogenesis when it acts in concert with other factors. A class of ubiquitous environmental chemicals that are hypothesized to potentially function in this low-dose capacity are synthesized polybrominated diphenyl ethers (PBDEs). PBDEs can affect correlates of carcinogenesis that include genomic instability and inflammation. However, the effect of low-dose PBDE exposure on such correlates in mammary tissue has not been examined. In the present study, low-dose long-term (16 weeks) administration of PBDE to mice modulated transcriptomic indicators of genomic integrity and innate immunity in normal mammary tissue. PBDE increased transcriptome signatures for the Nuclear Factor Erythroid 2 Like 2 (NFE2L2) response to oxidative stress and decreased signatures for non-homologous end joining DNA repair (NHEJ). PBDE also decreased transcriptome signatures for the cyclic GMP-AMP Synthase - Stimulator of Interferon Genes (cGAS-STING) response, decreased indication of Interferon Stimulated Gene Factor 3 (ISGF3) and Nuclear Factor Kappa B (NF-κB) transcription factor activity, and increased digital cytometry estimates of immature dendritic cells (DCs) in mammary tissue. Replication of the PBDE exposure protocol in mice susceptible to mammary carcinogenesis resulted in greater tumor development. The results support the notion that ongoing exposure to low levels of PBDE can disrupt facets of genomic integrity and innate immunity in mammary tissue. Such effects affirm that synthesized PBDEs are a class of environmental chemicals that reasonably fit the low-dose mixture hypothesis.
RNA sequencing and integrative analysis reveal pathways and hub genes associated with TGFβ1 stimulation on prostatic stromal cells
Authors: Xiang Peng , Du Zhen , Wang Mingdong , Liu Dan , Yan Wei , Hao Yongxiu , Liu Yutong , Guan Di , Ping Hao
Published: August 2022

Objective: Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. The transforming growth factor beta 1 (TGFβ1) plays an important role in the proliferation and differentiation of BPH stroma. However, it is not clear yet which important pathways and key genes are the downstream of TGFβ1 acting on prostatic stromal cells.

Methods: GSE132714 is currently the newer, available, and best high-throughput sequencing data set for BPH disease and includes the largest number of BPH cases. We examined the TGFβ1 expression level in BPH and normal prostate (NP) by analyzing the GSE132714 data set as well as carrying out immunohistochemistry of 15 BPH and 15 NP samples. Primary prostatic stromal cells (PrSCs) were isolated from five fresh BPH tissues. RNA sequencing and bioinformatics analysis were used to reveal important pathways and hub genes associated with TGFβ1 stimulation on PrSCs.

Results: TGFβ1 was upregulated in BPH stroma compared to NP stroma. A total of 497 genes (244 upregulated and 253 downregulated) were differentially expressed in PrSCs with and without TGFβ1 stimulation. The Gene Ontology revealed that differentially expressed genes (DEGs) were mainly enriched in progesterone secretion, interleukin-7 receptor binding, and CSF1-CSF1R complex. The Wnt signaling pathway, PI3K−Akt signaling pathway, JAK−STAT signaling pathway, and Hippo signaling pathway were screened based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. FN1, SMAD3, CXCL12, VCAM1, and ICAM1 were selected as hub genes according to the degree of connection from the protein–protein interaction (PPI) network.

Conclusion: This study sheds some new insights into the role of TGFβ1 in BPH stroma and provides some clues for the identification of potential downstream mechanisms and targets.
DNA Damage Repair and Current Therapeutic Approaches in Gastric Cancer: A Comprehensive Review
Authors: Wang Menghui , Xie Chuan
Published: August 2022

DNA in cells is frequently damaged by endogenous and exogenous agents. However, comprehensive mechanisms to combat and repair DNA damage have evolved to ensure genomic stability and integrity. Improper DNA damage repair may result in various diseases, including some types of tumors and autoimmune diseases. Therefore, DNA damage repair mechanisms have been proposed as novel antitumor drug targets. To date, numerous drugs targeting DNA damage mechanisms have been developed. For example, PARP inhibitors that elicit synthetic lethality are widely used in individualized cancer therapies. In this review, we describe the latent DNA damage repair mechanisms in gastric cancer, the types of DNA damage that can contribute to the development of gastric cancer, and new therapeutic approaches for gastric cancer that target DNA damage repair pathways.
The state of the art of extracellular vesicle research in protozoan infection
Authors: Wang Xinlei , Chen Jie , Zheng Jingtong
Published: August 2022

Protozoan diseases seriously affect the health of human beings, livestock and poultry and lead to high economic and medical costs. Extracellular vesicles (EVs) are membranous structures formed through biological processes that play important roles in immune regulation. Studies have shown that parasites transmit information to hosts through EVs to modulate host immune responses. The major roles played by EVs released from parasites involve facilitating parasitization of the host. In this review, we discuss relevant recently obtained data on EVs secreted by different kinds of protozoa, including their molecular mechanisms, and discuss the roles played by EVs in the occurrence and development of parasitic diseases.
Case report: Novel compound-heterozygous mutations in the TCN2 gene identified in a chinese girl with transcobalamin deficiency
Authors: Luo Juan , Guo Hongxi , Feng Lifang , Yang Luhong , Chen Xiaoqian , Du Tingting , Hu Man , Yao Hui , Chen Xiaohong
Published: August 2022

Transcobalamin (TC) deficiency is a rare autosomal recessive disease characterized by megaloblastic anemia. It is caused by cellular vitamin B12 depletion, which subsequently results in elevated levels of homocysteine and methylmalonic acid. This disease is usually diagnosed by genetic analysis of the TCN2 gene. Here, we described a 2.2-month-old Chinese girl with TC deficiency presenting with diarrhea, fever and poor feeding. Whole-exome sequencing detected a pair of compound-heterozygous mutations in TCN2 gene, c.754-12C>G and c.1031_1032delGA (p.R344Tfs*20). To our knowledge, it is the first time that they were identified and reported in TC deficiency. This study contributes to a better understanding of the TC deficiency, expanding the spectrum of TCN2 mutations in this disorder and also supporting the early diagnosis and proper treatment of similar cases in the future.
Genetic association-based functional analysis detects HOGA1 as a potential gene involved in fat accumulation
Authors: Kim Myungsuk , Park Kye Won , Ahn Yeongseon , Lim Eun Bi , Kwak Soo Heon , Randy Ahmad , Song No Joon , Park Kyong Soo , Nho Chu Won , Cho Yoon Shin
Published: August 2022

Although there are a number of discoveries from genome-wide association studies (GWAS) for obesity, it has not been successful in linking GWAS results to biology. We sought to discover causal genes for obesity by conducting functional studies on genes detected from genetic association analysis. Gene-based association analysis of 917 individual exome sequences showed that HOGA1 attains exome-wide significance (p-value < 2.7 × 10–6) for body mass index (BMI). The mRNA expression of HOGA1 is significantly increased in human adipose tissues from obese individuals in the Genotype-Tissue Expression (GTEx) dataset, which supports the genetic association of HOGA1 with BMI. Functional analyses employing cell- and animal model-based approaches were performed to gain insights into the functional relevance of Hoga1 in obesity. Adipogenesis was retarded when Hoga1 was knocked down by siRNA treatment in a mouse 3T3-L1 cell line and a similar inhibitory effect was confirmed in mice with down-regulated Hoga1. Hoga1 antisense oligonucleotide (ASO) treatment reduced body weight, blood lipid level, blood glucose, and adipocyte size in high-fat diet-induced mice. In addition, several lipogenic genes including Srebf1, Scd1, Lp1, and Acaca were down-regulated, while lipolytic genes Cpt1l, Ppara, and Ucp1 were up-regulated. Taken together, HOGA1 is a potential causal gene for obesity as it plays a role in excess body fat development.
I’ve looked at gut from both sides now: Gastrointestinal tract involvement in the pathogenesis of SARS-CoV-2 and HIV/SIV infections
Authors: Pandrea Ivona , Brooks Kelsie , Desai Rahul P. , Tare Minali , Brenchley Jason M. , Apetrei Cristian
Published: August 2022

The lumen of the gastrointestinal (GI) tract contains an incredibly diverse and extensive collection of microorganisms that can directly stimulate the immune system. There are significant data to demonstrate that the spatial localization of the microbiome can impact viral disease pathogenesis. Here we discuss recent studies that have investigated causes and consequences of GI tract pathologies in HIV, SIV, and SARS-CoV-2 infections with HIV and SIV initiating GI pathology from the basal side and SARS-CoV-2 from the luminal side. Both these infections result in alterations of the intestinal barrier, leading to microbial translocation, persistent inflammation, and T-cell immune activation. GI tract damage is one of the major contributors to multisystem inflammatory syndrome in SARS-CoV-2-infected individuals and to the incomplete immune restoration in HIV-infected subjects, even in those with robust viral control with antiretroviral therapy. While the causes of GI tract pathologies differ between these virus families, therapeutic interventions to reduce microbial translocation-induced inflammation and improve the integrity of the GI tract may improve the prognoses of infected individuals.
A rapid method for isolation of bacterial extracellular vesicles from culture media using epsilon-poly-L–lysine that enables immunological function research
Authors: Wei Shujin , Jiao Dian , Xing Wanli
Published: August 2022

Both Gram-negative and Gram-positive bacteria can release vesicle-like structures referred to as bacterial extracellular vesicles (BEVs), which contain various bioactive compounds. BEVs play important roles in the microbial community interactions and host-microbe interactions. Markedly, BEVs can be delivered to host cells, thus modulating the development and function of the innate immune system. To clarify the compositions and biological functions of BEVs, we need to collect these vesicles with high purity and bioactivity. Here we propose an isolation strategy based on a broad-spectrum antimicrobial epsilon-poly-L-lysine (ϵ-PL) to precipitate BEVs at a relatively low centrifugal speed (10,000 × g). Compared to the standard ultracentrifugation strategy, our method can enrich BEVs from large volumes of media inexpensively and rapidly. The precipitated BEVs can be recovered by adjusting the pH and ionic strength of the media, followed by an ultrafiltration step to remove ϵ-PL and achieve buffer exchange. The morphology, size, and protein composition of the ϵ-PL-precipitated BEVs are comparable to those purified by ultracentrifugation. Moreover, ϵ-PL-precipitated BEVs retained the biological activity as observed by confocal microscopy studies. And THP-1 cells stimulated with these BEVs undergo marked reprogramming of their transcriptome. KEGG analysis of the differentially expressed genes showed that the signal pathways of cellular inflammatory response were significantly activated. Taken together, we provide a new method to rapidly enrich BEVs with high purity and bioactivity, which has the potential to be applied to BEVs-related immune response studies.
The potential role of exosomal miRNAs and membrane proteins in acute HIV-infected people
Authors: Li Xin , Wang Wenjing , Chen Jing , Xie Bangxiang , Luo Shumin , Chen Dexi , Cai Chao , Li Chuanyun , Li Weihua
Published: August 2022

Exosomes play an important role during human immunodeficiency virus (HIV) acute infection. Yet, information regarding its cargo and its association with HIV rapid progressors (RPs) and typical progressors (TPs) remain largely unknown. In this study, exosomal miRNAs sequencing and mass cytometry were used to identify differential exosomal miRNAs and membrane proteins that participate in the pathogenesis of TPs and RPs. We discovered that miR-144-5p, miR-1180-3p, miR-451a, miR-362-5p, and miR-625-5p are associated with the TPs and miR-362-5p with the RPs. Decreased autophagy, amino acid metabolism, immune response, and IL-6 are closely related to RPs. In addition, SP1 was selected as the most significant transcription factor (TF) associated with disease progression. CD49D, CD5, CCR5, CD40, CD14, and CD86 were selected as the differential exosomal membrane proteins between TPs and RPs. This study provides valuable information for clarifying the mechanism in people with acute HIV infection.
Heterogeneity of tumor immune microenvironment and real-world analysis of immunotherapy efficacy in lung adenosquamous carcinoma
Authors: Li Chao , Zheng Xiaobin , Li Pansong , Wang Huijuan , Hu Jie , Wu Lin , Wang Zhijie , Guo Hui , Wu Fang , Zhong Wenzhao , Zhou Chengzhi , Chu Qian , Zhao Jun , Zheng Xinlong , Xiao Weijin , Zhu Weifeng , Zhang Longfeng , Li Qian , Jiang Kan , Miao Qian , Wu Biao , Xu Yiquan , Wu Shiwen , Wang Haibo , Yang Shanshan , Li Yujing , Xia Xuefeng , Yi Xin , Huang Cheng , Zhu Bo , Lin Gen
Published: August 2022

Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T-cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. Twenty-two (73.3%) patients were EGFR-positive. The TIME was defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) were predominantly expressed in squamous cell carcinoma components (SCCCs) versus adenocarcinoma components (ACCs), where enhanced CD4+ FOXP3+ regulatory T cell and attenuated CD57+ natural killer cell infiltration were present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCCs had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort III, the efficacy of ICI-based therapy was estimated using a real-world data of 46 ASCs from 11 centers. Majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. The overall objective response rate of 28%, median progression-free survival of 6.0 months (95% confidence interval [CI] 4.3–7.7), and median overall survival of 24.7 months (95% CI 7.2–42.2) were observed in the ICI-based treatment. This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACCs and SCCCs. Lung ASC patients have a moderate response to ICI-based immunotherapy.
Impaired functionality of antigen presenting cells in HIV- exposed uninfected infants in the first six months of life
Authors: Jalbert Emilie , Ghosh Tusharkanti , Smith Christiana , Amaral Fabiana R. , Mussi-Pinhata Marisa M. , Weinberg Adriana
Published: August 2022

HIV-exposed uninfected infants (HEU) have increased morbidity and mortality due to infections in the first 6 months of life that tapers down to 2 years of life. The underlying immunologic defects remain undefined. We investigated antigen-presenting cells (APC) by comparing the phenotype of unstimulated APC, responses to toll-like receptor (TLR) stimulation, and ability to activate natural killer (NK) cells in 24 HEU and 64 HIV-unexposed infants (HUU) at 1-2 days of life (birth) and 28 HEU and 45 HUU at 6 months of life. At birth, unstimulated APC showed higher levels of activation and cytokine production in HEU than HUU and stimulation with TLR agonists revealed lower expression of inflammatory cytokines and activation markers, but similar expression of IL10 regulatory cytokine, in APC from HEU compared to HUU. Differences were still present at 6 months of life. From birth to 6 months, APC underwent extensive phenotypic and functional changes in HUU and minimal changes in HEU. TLR stimulation also generated lower NK cell expression of CD69 and/or IFNγ in HEU compared with HUU at birth and 6 months. In vitro experiments showed that NK IFNγ expression depended on APC cytokine secretion in response to TLR stimulation. Ex vivo IL10 supplementation decreased APC-mediated NK cell activation measured by IFNγ expression. We conclude that APC maturation was stunted or delayed in the first 6 months of life in HEU compared with HUU. Deficient inflammatory APC responses and/or the imbalance between inflammatory and regulatory responses in HEU may play an important role in their increased susceptibility to severe infections.
Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis
Authors: Wang Lin , He Chengqi
Published: August 2022

Macrophages are the most abundant immune cells within the synovial joints, and also the main innate immune effector cells triggering the initial inflammatory responses in the pathological process of osteoarthritis (OA). The transition of synovial macrophages between pro-inflammatory and anti-inflammatory phenotypes can play a key role in building the intra-articular microenvironment. The pro-inflammatory cascade induced by TNF-α, IL-1β, and IL-6 is closely related to M1 macrophages, resulting in the production of pro-chondrolytic mediators. However, IL-10, IL1RA, CCL-18, IGF, and TGF are closely related to M2 macrophages, leading to the protection of cartilage and the promoted regeneration. The inhibition of NF-κB signaling pathway is central in OA treatment via controlling inflammatory responses in macrophages, while the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway appears not to attract widespread attention in the field. Nrf2 is a transcription factor encoding a large number of antioxidant enzymes. The activation of Nrf2 can have antioxidant and anti-inflammatory effects, which can also have complex crosstalk with NF-κB signaling pathway. The activation of Nrf2 can inhibit the M1 polarization and promote the M2 polarization through potential signaling transductions including TGF-β/SMAD, TLR/NF-κB, and JAK/STAT signaling pathways, with the regulation or cooperation of Notch, NLRP3, PI3K/Akt, and MAPK signaling. And the expression of heme oxygenase-1 (HO-1) and the negative regulation of Nrf2 for NF-κB can be the main mechanisms for promotion. Furthermore, the candidates of OA treatment by activating Nrf2 to promote M2 phenotype macrophages in OA are also reviewed in this work, such as itaconate and fumarate derivatives, curcumin, quercetin, melatonin, mesenchymal stem cells, and low-intensity pulsed ultrasound.
Case report: A pediatric case of Bickerstaff brainstem encephalitis after COVID-19 vaccination and Mycoplasma pneumoniae infection: Looking for the culprit
Authors: Monte Gabriele , Pro Stefano , Ursitti Fabiana , Ferilli Michela Ada Noris , Moavero Romina , Papetti Laura , Sforza Giorgia , Bracaglia Giorgia , Vigevano Federico , Palma Paolo , Valeriani Massimiliano
Published: August 2022

Bickerstaff brainstem encephalitis (BBE) is a rare, immune-mediated disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance. It has a complex multifactorial etiology, and a preceding infectious illness is seen in the majority of cases. Immune-mediated neurological syndromes following COVID-19 vaccination have been increasingly described. Here we report the case of a child developing BBE 2 weeks after COVID-19 vaccination. Despite nerve conduction studies and CSF analysis showing normal results, BBE was diagnosed on clinical ground and immunotherapy was started early with a complete recovery. Later, diagnosis was confirmed by positive anti-GQ1b IgG in serum. Even if there was a close temporal relationship between disease onset and COVID-19 vaccination, our patient also had evidence of a recent Mycoplasma pneumoniae infection that is associated with BBE. Indeed, the similarity between bacterial glycolipids and human myelin glycolipids, including gangliosides, could lead to an aberrantly immune activation against self-antigens (i.e., molecular mimicry). We considered the recent Mycoplasma pneumoniae infection a more plausible explanation of the disease onset. Our case report suggests that suspect cases of side effects related to COVID-19 vaccines need a careful evaluation in order to rule out well-known associated factors before claiming for a causal relationship.
Win some, lose some: The ecophysiology of Porites astreoides as a key coral species to Caribbean reefs
Authors: Lima Lais F.O. , Bursch Hayden , Dinsdale Elizabeth A.
Published: August 2022

Caribbean reefs have undergone large-scale losses in coral cover in past decades, sparking a search for species that are resilient under stress. Porites astreoides has been considered a “winner” and a key player in sustaining coral cover in the Caribbean as more sensitive species struggle. However, P. astreoides has recently declined in abundance, raising concern about its status as a winner. Here, we reviewed the ecophysiology of P. astreoides in response to environmental stress to elucidate whether this species could thrive in the future of Caribbean reefs. We examined ecophysiological variables of P. astreoides related to photosynthesis, growth, recruitment, tissue condition, and microbiome in response to temperature, pH, macroalgal competition, depth, and sedimentation. Overall, P. astreoides was sensitive to environmental stress and each physiological feature showed varying levels of sensitivity. Coral-algal photosynthesis and coral tissue condition could withstand single events of thermal stress but reflected a metabolic imbalance that hinders recovery from repeated bleaching events, compromising long-term success. Colony growth was particularly vulnerable to low pH and macroalgal competition. Recruitment was unaffected, or even favored, by depth and could tolerate high temperatures, but it was sensitive to exposure to macroalgae, especially in combination with abiotic stressors. The response of the microbiome of P. astreoides to stressors is still poorly understood. In relation to other corals, P. astreoides was frequently reported as the most sensitive species in the reviewed literature. The success of P. astreoides is tightly integrated into the future of Caribbean reefs, which could be losing an old winner.
Interactive effects of fishing effort reduction and climate change in a central Mediterranean fishing area: Insights from bio-economic indices derived from a dynamic food-web model
Authors: Agnetta Davide , Badalamenti Fabio , Colloca Francesco , Cossarini Gianpiero , Fiorentino Fabio , Garofalo Germana , Patti Bernardo , Pipitone Carlo , Russo Tommaso , Solidoro Cosimo , Libralato Simone
Published: August 2022

Disentangling the effects of mixed fisheries and climate change across entire food-webs requires a description of ecosystems using tools that can quantify interactive effects as well as bio-economic aspects. A calibrated dynamic model for the Sicily Channel food web, made up of 72 functional groups and including 13 fleet segments, was developed. A temporal simulation until 2050 was conducted to evaluate the bio-economic interactive effects of the reduction of bottom trawling fishing effort by exploring different scenarios that combine fishery and climate change. Our results indicate that direct and indirect effects produce a net increase in biomass of many functional groups with immediate decline of trawlers’ catches and economic incomes, followed by a long term increase mainly due to biomass rebuilding of commercial species which lasts 5-10 years after fishing reduction. Synergistic and antagonistic effects caused by changes in the fishing effort and in climate characterize a specific functional group’s response in biomass which, in turn, modulate also the catch and income of the other fleets, and especially of those sharing target resources. However, trawler’s intra-fleet competition is higher than the others fleet effects. In the medium term, the effects of fishing effort reduction are higher than those of climate change and seem to make exploitation of marine resources more sustainable over time and fishery processes more efficient by improving ecosystem health.
Microbial community characteristics of the intestine and gills of medium-form populations of Sthenoteuthis oualaniensis in the South China Sea
Authors: Hu Xiaojuan , Su Haochang , Zhang Peng , Chen Zuozhi , Xu Yu , Xu Wujie , Li Jie , Wen Guoliang , Cao Yucheng
Published: August 2022

Sthenoteuthis oualaniensis (purpleback squid) is an excellent biological resource in the South China Sea. However, the microbiological characteristics of this South China Sea squid, especially those of the medium-form of different sexes and gonadal maturities, are poorly understood. In this study, the characteristics of the bacterial community in the intestinal and gill tissues of female and male S. oualaniensis with different gonadal maturities, collected from the Nansha Sea of China in spring 2020, were analyzed. The results showed that Tenericutes, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in the intestinal microbial samples of female immature gonad (FN), male immature gonad (MN), and male sexual maturity (MY) samples of the S. oualaniensis populations. Proteobacteria, Firmicutes, Bacteroidetes, and Tenericutes were the dominant phyla in the intestinal microbial sample of the female sexual maturity (FY) group. The microbial community in the gills differed from that of the intestinal flora. The dominant phyla in the gill samples were Proteobacteria, Firmicutes, and Bacteroidetes, regardless of sex or gonadal maturity. According to the random forest analysis, the gill samples had significantly (p<0.001) more Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the top 20 than the intestinal samples. Correlation analysis showed that the mantle length of S. oualaniensis was significantly (p<0.05) negatively correlated with the abundance of Tenericutes, but significantly (p<0.01) positively correlated with Firmicutes and Bacteroidetes. The mantle length of FY was significantly (p<0.05) longer than that of the other types. The results indicated that the differences in the intestinal bacterial community were related to the growth and feeding characteristics of S. oualaniensis of different sexes and maturities.
Pharmacokinetics of Dantrolene in the Plasma Exchange Treatment of Malignant Hyperthermia in a 14-Year-Old Chinese Boy: A Case Report and Literature Review
Authors: Li Xiaoxiao , Li Chao , Zhou Yang , Li Zhengqian , Xiong Xin , Wang Chuhui , Zhou Congya , Han Bin , Yang Li , Guo Xiangyang
Published: August 2022

Malignant hyperthermia (MH) is a rare life-threatening response that is triggered by exposure to specific anesthetics commonly used during surgical interventions. Dantrolene is a well-known drug used as the first-line therapy for MH. A 14-year-old Chinese boy with a mutation in type 1 Ryanodine receptor (RyR1) whose muscle biopsy diagnosis was central core disease (CCD) had an occurrence of MH after a cervical spine surgery, during which he was placed under general anesthesia without volatile anesthetics or succinylcholine. The MH crisis treatment workflow was started and intravenous dantrolene was used, which was soon combined with sequent continuous veno-venous hemofiltration (CVVH) and plasma exchange (PE) therapy. We explored the pharmacokinetic profile of dantrolene during PE treatment. It showed that a one-compartment model with first-order kinetics was sufficient to characterize dantrolene pharmacokinetics (PK). The renal clearance estimate for dantrolene was 0.33 mL/(min*kg) and the volume of distribution was 0.51 L/kg. Though a 4-h PE elevated about 27% off-clearance for dantrolene, it eliminated extra dantrolene by a mere 4% of the area under the curve (AUC). We made no recommendation with respect to adjusting dantrolene dosing for MH adolescents with a 4-h PE.
Comparison of clinically indicated replacement and routine replacement of peripheral intravenous catheters: A systematic review and meta-analysis of randomized controlled trials
Authors: Chen Ching-Yi , Chen Wang-Chun , Chen Jung-Yueh , Lai Chih-Cheng , Wei Yu-Feng
Published: August 2022

Background

It is unknown whether clinically indicated replacement of peripheral intravenous catheters (PIVCs) increases the risks of PIVC-associated complications and infections compared to routine replacement of PIVCs.

Methods

We searched PubMed, the Web of Science, the Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov for randomized controlled trials (RCTs) that compare the safety outcomes of routine replacement and clinically indicated replacement of PIVCs were included for meta-analysis. The primary outcome was the incidence of phlebitis, and secondary outcomes included the risks of occlusion, local infection, infiltration, catheter-related bloodstream infection (CRBSI), and accidental removal of the PIVC.

Results

A total of 9 RCTs involving 10 973 patients were included in this meta-analysis, of whom 5,546 and 5,527 were assigned to the study group (clinically indicated replacement of PIVCs) and control group (routine replacement of PIVCs every 72–96 h), respectively. The incidence of phlebitis in the study group was significantly higher than that in the control group [risk ratio (RR), 1.20; 95% confidence interval (CI), 1.01–1.44, P = 0.04, I2 = 49%]. In addition, the study group was associated with a higher risk of occlusion (RR, 1.45; 95% CI, 1.08–1.95, P = 0.01, I2 = 82%) and infiltration (fluid leaks) (RR, 1.27; 95% CI, 1.06–1.53, P = 0.01, I2 = 72%) than the control group. However, no significant differences were observed in the risks of local infection (RR, 1.75; 95% CI, 0.38–8.16, P = 0.48, I2 = 0%) and CRBSI (RR, 0.61; 95% CI, 0.08–4.68, P = 0.64, I2 = 0%) between the study and control groups.

Conclusion

The clinically indicated replacement of PIVCs may increase the risks of PIVC-associated phlebitis, infiltration, and occlusion compared to the routine replacement of PIVCs, but did not increase the risk of PIVC-associated infections. Based on these findings, routine replacement of PIVCs every 72–96 h maybe a preferred option than clinically indicated replacement of PIVCs.

Systematic review registration

[www.crd.york.ac.uk/prospero/], identifier [CRD42022302021].
Dysbiosis and predicted function of dental and ruminal microbiome associated with bovine periodontitis
Authors: Borsanelli Ana C. , Athayde Flávia R. F. , Riggio Marcello P. , Brandt Bernd W. , Rocha Fernando I. , Jesus Ederson C. , Gaetti-Jardim Elerson , Schweitzer Christiane M. , Dutra Iveraldo S.
Published: August 2022

Extensive cattle livestock is advancing in Amazonia and its low productivity, with consequent pressure to open new areas, is partly due to sanitary problems and, among them, the periodontal diseases, whose environmental triggers or modifying factors are unknown. In this study, we used high-throughput sequencing, network analysis and predicted functions to investigate the dental and ruminal microbiota of cattle raised in new livestock areas in the Amazon and identify possible keystone pathogens and proteins associated with the disease. Ninety-three genera were common in dental and ruminal fluid microbiomes and among them periodontal pathogens such as Fusobacterium, Prevotella, Porphyromonas and Actinomyces were recognized. Network analysis showed that dental microbiomes of clinically healthy animals tend to comprise a group of OTUs in homeostasis and when analyzed together, dental and ruminal fluid microbiomes of animals with periodontitis had almost twice the number of negative edges, indicating possible competition between bacteria and dysbiosis. The incisor dental and ruminal fluid microbiomes were dominated by a core community composed of members of the phyla Firmicutes and Bacteroidetes. Network results showed that members of the Prevotella genus stood out among the top five OTUs, with the largest number of hubs in the dental and ruminal microbiota of animals with periodontitis. Protein families linked to an inflammatory environment were predicted in the dental and ruminal microbiota of cattle with periodontitis. The dissimilarity between dental microbiomes, discriminating between healthy cattle and those with periodontitis and the identification of possible key pathogens, represent an important reference to elucidate the triggers involved in the etiopathogenesis of bovine periodontitis, and possibly in the development of measures to control the disease and reduce the pressures for deforestation.
Deficiency of migration inhibitory factor influences the gut microbiota of C57BL/6 mice infected with Plasmodium berghei ANKA
Authors: Xie Yiting , Guan Wei , Zhao Yanqing , Yan Siyi , Guo Kun , Chen Sirui , Hu Xinyi , Shi Haimei , Li Jian
Published: August 2022

Cerebral malaria (CM), as one of the most common complications in severe malaria, has threatened millions of individuals’ neurological health and even their lives. Macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory factor in humans, seems to be a risk factor for death in patients with CM, but its functional mechanism remains unclear. To verify whether affecting the intestinal microbes of the host was one of the mechanisms by which MIF regulates CM, C57BL/6 mice, including WT + PbA, MIF-KO + PbA and their uninfected controls, were sent for 16S rRNA-based sequencing targeting the V4 region of the intestinal microbiota through the Illumina MiSeq platform. The results showed that OTU clustering, alpha and beta diversity in the four groups involved had evident variation. The relative abundance at different taxonomic levels, especially the dominant intestinal flora, was obviously changed. The LEfSe analysis screened out several biomarkers, including significantly reduced Ligilactobacillus (Lactobacillus murinus) in WPbA mice compared to the WT group and Akkermansia (Akkermansia_muciniphila) in KPbA mice compared to the WPbA group. For MIF KO groups, mice infected with PbA or uninfected showed significant enrichment of producers of short-chain fatty acids, including Dubosiella and Faecalibaculum (Faecalibaculum rodentium) in KPbA, and Lachnospiraceae_NK4A136_group and Firmicutes_bacterium_M10-2 in KO. This study not only further proved the gut microbiota changes in C57BL/6 mice caused by PbA infection, but also found that MIF deletion directly affected the changes in the gut microbiota of C57BL/6 mice before and after PbA infection. This finding reveals a potential mechanism by which MIF regulates CM. Combining MIF with potential microbial biomarkers will provide a promising idea to develop combined drugs for improving CM in the future.
Multimodal magnetic resonance imaging reveals distinct sensitivity of hippocampal subfields in asymptomatic stage of Alzheimer’s disease
Authors: Wu Junjie , Shahid Syed S. , Lin Qixiang , Hone-Blanchet Antoine , Smith Jeremy L. , Risk Benjamin B. , Bisht Aditya S. , Loring David W. , Goldstein Felicia C. , Levey Allan I. , Lah James J. , Qiu Deqiang
Published: August 2022

While hippocampal atrophy and its regional susceptibility to Alzheimer’s disease (AD) are well reported at late stages of AD, studies of the asymptomatic stage of AD are limited but could elucidate early stage pathophysiology as well as provide predictive biomarkers. In this study, we performed multi-modal magnetic resonance imaging (MRI) to estimate morphometry, functional connectivity, and tissue microstructure of hippocampal subfields in cognitively normal adults including those with asymptomatic AD. High-resolution resting-state functional, diffusion and structural MRI, cerebral spinal fluid (CSF), and neuropsychological evaluations were performed in healthy young adults (HY: n = 40) and healthy older adults with negative (HO−: n = 47) and positive (HO+ : n = 25) CSF biomarkers of AD. Morphometry, functional connectivity, and tissue microstructure were estimated from the structural, functional, and diffusion MRI images, respectively. Our results indicated that normal aging affected morphometry, connectivity, and microstructure in all hippocampal subfields, while the subiculum and CA1-3 demonstrated the greatest sensitivity to asymptomatic AD pathology. Tau, rather than amyloid-β, was closely associated with imaging-derived synaptic and microstructural measures. Microstructural metrics were significantly associated with neuropsychological assessments. These findings suggest that the subiculum and CA1-3 are the most vulnerable in asymptomatic AD and tau level is driving these early changes.