bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on stimulating mechanism and restricting factors of employees’ innovative behaviour under COVID-19
Authors: Wu Guosong
Published: August 2022

Innovation is the foundation of an enterprise’s survival and development. Employee innovation is the source of enterprise innovation. Under the COVID-19 epidemic, staff innovation is crucial to whether an enterprise can transform a crisis into an opportunity. However, the negative emotions caused by the epidemic will hinder staff innovation. The influence of the COVID-19 pandemic in China was investigated from May 2020 to October 2021 by using questionnaires. This study explores the motivating mechanism and restricting factors of employees’ innovative behaviour under sudden public crisis events. The software SPSS 22.0 is used for the descriptive statistical and correlation analyses of the collected data. Enterprise managers need to study the influencing factors of employees’ innovative behaviour under the COVID-19 epidemic to solve the problem of employees’ negative emotions. Based on the statistical analysis of 639 valid questionnaires for employees of high-tech enterprises, this study explores the motivating mechanism and influencing factors of employees’ innovative behaviour from the aspects of positive psychological quality and leaders’ interpersonal emotion management. This study also uses work autonomy as a mediating variable to verify its mediating role in the process of employees’ positive psychological quality and leaders’ interpersonal emotion management on innovation behaviour. This study tested the moderating effect of employees’ perceived corporate social responsibility on the relationship between employees’ positive psychological quality, leaders’ interpersonal emotion management and innovative behaviour. Through the statistical analysis of 639 valid questionnaires of employees in high-tech enterprises, the relevant model assumptions are verified. Therefore, under the COVID-19 pandemic, enterprises should take responsibility from the aspect of caring for employees to promote the positive effect of employees’ psychological attitudes on work results. This study provides countermeasures to ensure the smooth progress of employee innovation activities.
Resource utilization of waste tailings: Simulated removal of nitrogen from secondary effluent by autotrophic denitrification based on pyrite tailings
Authors: Mao Jie , He Mengqi , Qin Ying , Chen You , Wang Xinyu , Che Haojie , Cheng Chun , Wang Tiantian , Wang Wenliang , Sun Bai , Zhu Shuguang
Published: August 2022

In this report, eco-friendly and low-cost pyrite tailings are utilized as denitrification materials, while pyrite and magnetite are used as the control experimental groups to explore the denitrification performance of pyrite tailings. The results show that the removal effect of pyrite tailings on NO3− is slightly lower than that of pyrite. However, the concentration of NH4+ decreased, and the effluent SO42- concentration was lower than that of pyrite. In addition, pyrite with different particle sizes is prepared by the ball milling method, and the effect of particle size on the denitrification performance of pyrite is studied. The results show that with the decrease in particle size, microorganisms are more likely to use S in tailings as electron donors, the denitrification rate is faster, and the denitrification effect was better at the same time.
Delineating and characterizing critical habitat for the Eastern Pacific olive ridley turtle (Lepidochelys olivacea): Individual differences in migratory routes present challenges for conservation measures
Authors: Figgener Christine , Bernardo Joseph , Plotkin Pamela T.
Published: August 2022

The effective conservation of highly migratory marine species is only possible if core areas of activity and critical habitat can be identified within the vast and dynamic oceanic environment and later on used to delineate marine protected areas (MPAs). However, gathering population-level data and identifying universal patterns within a species or population can be difficult when only a small sample size exists and individuals are not ecologically interchangeable. In addition, the open ocean beyond the Exclusive Economic Zone (EEZ) of a country is considered the high-seas and is not part of any jurisdiction and therefore challenging to govern by laws. Granting protection to species using these waters is sometimes virtually impossible. Another challenge is the dynamic nature of the oceanic environment. MPAs are usually based on spatially explicit and static areas, but migratory routes can shift following available food, currents, and temperatures or else, potentially rendering designated areas useless. The red-listed olive ridley turtle is known for its nomadic migratory and feeding behavior and a divergent nesting strategy among females. Our study used two approaches to identify critical habitats for the population nesting in Costa Rica and feeding in the Eastern Tropical Pacific. One was based on a static Kernel Density Approach to identify core areas. The other was a habitat preference model that took into account changing environmental variables such as sea surface temperature and chlorophyll-a concentrations. We were able to identify core areas at the population level by pooling two datasets and increasing our sample size. Our habitat preference model showed a high correlation of olive ridley presence with all tested environmental variables, except chlorophyll-a concentration. Our results reveal that olive ridleys use mainly regions that fall within EEZs and, therefore, the jurisdiction of six countries in Central America and provide an essential conservation tool.
California’s forest carbon offsets buffer pool is severely undercapitalized
Authors: Badgley Grayson , Chay Freya , Chegwidden Oriana S. , Hamman Joseph J. , Freeman Jeremy , Cullenward Danny
Published: August 2022

California operates a large forest carbon offsets program that credits carbon stored in forests across the continental United States and parts of coastal Alaska. These credits can be sold to buyers who wish to justify ongoing emissions, including in California’s cap-and-trade program. Although fossil CO2 emissions have effectively permanent atmospheric consequences, carbon stored in forests is inherently less durable because forests are subject to significant socioeconomic and physical risks that can cause temporarily stored carbon to be re-released into the atmosphere. To address these risks, California’s program is nominally designed to provide a 100-year guarantee on forest carbon claims based on a self-insurance program known as a buffer pool. Projects contribute credits to the buffer pool based on a suite of project-specific risk factors, with buffer pool credits retired as needed to cover carbon losses from events such as wildfire or drought. So long as the buffer pool remains solvent, the program’s permanence claim remains intact. Here, we perform an actuarial analysis of the performance of California’s buffer pool. We document how wildfires have depleted nearly one-fifth of the total buffer pool in less than a decade, equivalent to at least 95 percent of the program-wide contribution intended to manage all fire risks for 100 years. We also show that potential carbon losses from a single forest disease, sudden oak death, could fully encumber all credits set aside for disease and insect risks. These findings indicate that California’s buffer pool is severely undercapitalized and therefore unlikely to be able to guarantee the environmental integrity of California’s forest offsets program for 100 years.
Application of apoptosis-related genes in a multiomics-related prognostic model study of gastric cancer
Authors: Xu Chengfei , Liu Zilin , Yan Chuanjing , Xiao Jiangwei
Published: August 2022

Gastric cancer (GC) is one of the most common tumors in the world, and apoptosis is closely associated with GC. A number of therapeutic methods have been implemented to increase the survival in GC patients, but the outcomes remain unsatisfactory. Apoptosis is a highly conserved form of cell death, but aberrant regulation of the process also leads to a variety of major human diseases. As variations of apoptotic genes may increase susceptibility to gastric cancer. Thus, it is critical to identify novel and potent tools to predict the overall survival (OS) and treatment efficacy of GC. The expression profiles and clinical characteristics of TCGA-STAD and GSE15459 cohorts were downloaded from TCGA and GEO. Apoptotic genes were extracted from the GeneCards database. Apoptosis risk scores were constructed by combining Cox regression and LASSO regression. The GSE15459 and TCGA internal validation sets were used for external validation. Moreover, we explored the relationship between the apoptosis risk score and clinical characteristics, drug sensitivity, tumor microenvironment (TME) and tumor mutational burden (TMB). Finally, we used GSVA to further explore the signaling pathways associated with apoptosis risk. By performing TCGA-STAD differential analysis, we obtained 839 differentially expressed genes, which were then analyzed by Cox regressions and LASSO regression to establish 23 genes associated with apoptosis risk scores. We used the test validation cohort from TCGA-STAD and the GSE15459 dataset for external validation. The AUC values of the ROC curve for 2-, 3-, and 5-years survival were 0.7, 0.71, and 0.71 in the internal validation cohort from TCGA-STAD and 0.77, 0.74, and 0.75 in the GSE15459 dataset, respectively. We constructed a nomogram by combining the apoptosis risk signature and some clinical characteristics from TCGA-STAD. Analysis of apoptosis risk scores and clinical characteristics demonstrated notable differences in apoptosis risk scores between survival status, sex, grade, stage, and T stage. Finally, the apoptosis risk score was correlated with TME characteristics, drug sensitivity, TMB, and TIDE scores.
The prognostic value and clinical significance of mitophagy-related genes in hepatocellular carcinoma
Authors: Xu Wei , Zhao Dongxu , Huang Xiaowei , Zhang Man , Yin Minyue , Liu Lu , Wu Hongyu , Weng Zhen , Xu Chunfang
Published: August 2022

Background: Mitophagy has been found to play a significant part in the cancer process in a growing number of studies in recent years. However, there is still a lack of study on mitophagy-related genes’ (MRGs) prognostic potential and clinical significance in hepatocellular carcinoma (HCC).

Methods: We employed bioinformatics and statistical knowledge to examine the transcriptome data of HCC patients in the TCGA and GEO databases, with the goal of constructing a multigene predictive model. Then, we separated the patients into high- and low-risk groups based on the score. The model’s dependability was determined using principal components analysis (PCA), survival analysis, independent prognostic analysis, and receiver operating characteristic (ROC) analysis. Following that, we examined the clinical correlations, pharmacological treatment sensitivity, immune checkpoint expression, and immunological correlations between patients in high and low risk groups. Finally, we evaluated the variations in gene expression between high- and low-risk groups and further analyzed the network core genes using protein-protein interaction network analysis.

Results: Prognostic models were built using eight genes (OPTN, ATG12, CSNK2A2, MFN1, PGAM5, SQSTM1, TOMM22, TOMM5). During validation, the prognostic model demonstrated high reliability, indicating that it could accurately predict the prognosis of HCC patients. Additionally, we discovered that typical HCC treatment medicines had varying impacts on patients classified as high or low risk, and that individuals classified as high risk are more likely to fail immunotherapy. Additionally, the high-risk group expressed more immunological checkpoints. The immunological status of patients in different risk categories varies as well, and patients with a high-risk score have a diminished ability to fight cancer. Finally, PPI analysis identified ten related genes with potential for research.

Conclusion: Our prognostic model had good and reliable predictive ability, as well as clinical diagnosis and treatment guiding significance. Eight prognostic MRGs and ten network core genes merited further investigation.
Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker
Authors: Zhang Chi , Zeng Yuanxiao , Guo Xiuchen , Shen Hangjing , Zhang Jianhao , Wang Kaikai , Ji Mengmeng , Huang Shengwei
Published: August 2022

Background: The latest research identified cuproptosis as an entirely new mechanism of cell death. However, as a key regulator in copper-induced cell death, the prognostic and immunotherapeutic value of FDX1 in pan-cancer remains unclear.

Methods: Data from the UCSC Xena, GEPIA, and CPTAC were analyzed to conduct an inquiry into the overall differential expression of FDX1 across multiple cancer types. The expression of FDX1 in GBM, LUAD and HCC cell lines as well as their control cell lines was verified by RT-QPCR. The survival prognosis, clinical features, and genetic changes of FDX1 were also evaluated. Finally, the relationship between FDX1 and immunotherapy response was further explored through Gene Set Enrichment Analysis enrichment analysis, tumor microenvironment, immune cell infiltration, immune gene co-expression and drug sensitivity analysis.

Results: The transcription and protein expression of FDX1 were significantly reduced in most cancer types and had prognostic value for the survival of certain cancer patients such as ACC, KIRC, HNSC, THCA and LGG. In some cancer types, FDX1 expression was also markedly correlated with the clinical characteristics, TMB, MSI, and antitumor drug susceptibility or resistance of different tumors. Gene set enrichment analysis showed that FDX1 was significantly associated with immune-related pathways. Moreover, the expression level of FDX1 was confirmed to be strongly correlated with immune cell infiltration, immune checkpoint genes, and immune regulatory genes to a certain extent.

Conclusion: This study comprehensively explored the potential value of FDX1 as a prognostic and immunotherapeutic marker for pan-cancer, providing new direction and evidence for cancer therapy.
Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis
Authors: Wu Gan , Liu Can , Cao Ben , Cao Zelin , Zhai Haige , Liu Bin , Jin Shengwei , Yang Xinyu , Lv Chen , Wang Jianguang
Published: August 2022

Connective tissue growth factor (CTGF) has been recently acknowledged as an ideal biomarker in the early disease course, participating in the pathogenesis of pannus formation in rheumatoid arthritis (RA). However, existing approaches for the detection of or antagonist targeting CTGF are either lacking or unsatisfactory in the diagnosis and treatment of RA. To address this, we synthesized and screened high-affinity single-stranded DNA aptamers targeting CTGF through a protein-based SELEX procedure. The structurally optimized variant AptW2-1-39-PEG was characterized thoroughly for its high-affinity (KD 7.86 nM), sensitivity (minimum protein binding concentration, 2 ng), specificity (negative binding to other biomarkers of RA), and stability (viability-maintaining duration in human serum, 48 h) properties using various biochemical and biophysical assays. Importantly, we showed the antiproliferative and antiangiogenic activities of the aptamers obtained using functional experiments and further verified the therapeutic effect of the aptamers on joint injury and inflammatory response in collagen-induced arthritis (CIA) mice, thus advancing this study into actual therapeutic application. Furthermore, we revealed that the binding within AptW2-1-39-PEG/CTGF was mediated by the thrombospondin 1 (TSP1) domain of CTGF using robust bioinformatics tools together with immunofluorescence. In conclusion, our results revealed a novel aptamer that holds promise as an additive or alternative approach for CTGF-targeting diagnostics and therapeutics for RA.
Acute Lyme disease IgG N-linked glycans contrast the canonical inflammatory signature
Authors: Haslund-Gourley Benjamin Samuel , Grauzam Stéphane , Mehta Anand S. , Wigdahl Brian , Comunale Mary Ann
Published: August 2022

Lyme disease (LD) infection is caused by Borrelia burgdorferi sensu lato (Bb). Due to the limited presence of this pathogen in the bloodstream in humans, diagnosis of LD relies on seroconversion. Immunoglobulins produced in response to infection are differentially glycosylated to promote or inhibit downstream inflammatory responses by the immune system. Immunoglobulin G (IgG) N-glycan responses to LD have not been characterized. In this study, we analyzed IgG N-glycans from cohorts of healthy controls, acute LD patient serum, and serum collected after acute LD patients completed a 2- to 3-week course of antibiotics and convalesced for 70-90 days. Results indicate that during the acute phase of Bb infection, IgG shifts its glycosylation profile to include structures that are not associated with the classic proinflammatory IgG N-glycan signature. This unexpected result is in direct contrast to what is reported for other inflammatory diseases. Furthermore, IgG N-glycans detected during acute LD infection discriminated between control, acute, and treated cohorts with a sensitivity of 75-100% and specificity of 94.7-100%.
The versatility of macrophage heterogeneity in liver fibrosis
Authors: Gao Chun-Chen , Bai Jian , Han Hua , Qin Hong-Yan
Published: August 2022

Liver fibrosis is a highly conserved wound healing response to liver injury, characterized by excessive deposition of extracellular matrix (ECM) in the liver which might lead to loss of normal functions. In most cases, many types of insult could damage hepatic parenchymal cells like hepatocytes and/or cholangiocytes, and persistent injury might lead to initiation of fibrosis. This process is accompanied by amplified inflammatory responses, with immune cells especially macrophages recruited to the site of injury and activated, in order to orchestrate the process of wound healing and tissue repair. In the liver, both resident macrophages and recruited macrophages could activate interstitial cells which are responsible for ECM synthesis by producing a variety of cytokines and chemokines, modulate local microenvironment, and participate in the regulation of fibrosis. In this review, we will focus on the main pathological characteristics of liver fibrosis, as well as the heterogeneity on origin, polarization and functions of hepatic macrophages in the setting of liver fibrosis and their underlying mechanisms, which opens new perspectives for the treatment of liver fibrosis.
Three types of pulsed signal trains emitted by Indo-Pacific humpback dolphins (Sousa chinensis) in Beibu Gulf, South China Sea
Authors: Wang Xiao-yan , Jiang Ying , Liu Zong-wei , Yang Chun-mei , Chen Bing-yao , Lü Lian-gang
Published: August 2022

Pulsed signal trains comprising clicks, buzzes, and burst-pulses play important roles in the life activities of odontocetes, but they have not been distinguished in Indo-Pacific humpback dolphins. Underwater vocalizations of this species were recorded from 27 September to 2 October 2019 in the Beibu Gulf, South China Sea. Pulsed signal trains were detected with variations in the pulsed signal number (range of 6–76), mean inter-pulse interval (IPIs_m: 0.1–315 ms), and mean duration (D ranged from tens to thousands of milliseconds). Principal component analysis and hierarchical cluster analysis based on six acoustic parameters in the pulsed signal trains identified three categories of trains designated as clicks, burst-pulses, and buzzes. Buzzes and burst-pulses (different from those described in previous research) were detected for the first time in Indo-Pacific humpback dolphins in China. The results indicated that the IPIs_m was longest for clicks but shortest for buzzes, and the D values were longer for both clicks and burst-pulses than buzzes. The three train types could be identified based on the IPIs_m, with threshold values of 4.9 and 15.5 ms. The significant variations in the three vocalization types were related to surface behaviors, and buzzes could have a special function in foraging by this species, thereby requiring further research. These findings may facilitate future quantitative evaluations of the echolocation performance in wild Indo-Pacific humpback dolphins and provide important guidance regarding acoustic observations and the identification of this species.
Design selection and dynamic response analysis of CFG pile composite foundation in soft soil areas
Authors: Zhang Huahua , Liu Liming , Feng Wei , Zhou Yuru , Zheng Wei , Zhao Bingqin
Published: August 2022

The construction of roads along rivers plays a crucial role in the construction of economic belts and social and economic development along rivers. Roadbeds are the foundation of highway construction, while the soft soil foundation is widely distributed on both sides of rivers, resulting in some difficulties for roadbed construction and highway use. Despite diverse technical methods for the treatment of general roadbeds, the treatment of soft soil roadbeds should be further explored. In this paper, various advantages of applying CFG (Cement Fly-ash Gravels) pile treatment to the soft foundation in Bailinhe Road, Yichang are investigated. Specifically, the soft soil roadbed treated by CFG pile is numerically simulated, the changes in engineering index response before and after foundation treatment are analyzed, and then the dynamic analysis under vehicle dynamic load is performed. The results demonstrate that the reinforcement effect of the CFG pile significantly weakens the influence of vehicle dynamic load on roadbeds.
Adeno-associated virus-mediated expression of activated factor V (FVa) for hemophilia phenotypic correction
Authors: Sun Junjiang , Chen Xiaojing , Chai Zheng , Niu Hongqian , Dobbins Amanda L. , Nichols Timothy C. , Li Chengwen
Published: August 2022

Adeno-associated virus (AAV) gene therapy has been successfully applied in hemophilia patients excluding patients with inhibitors. During the coagulation pathway, activated factor V (FVa) functions downstream as a cofactor of activated factor X (FXa) to amplify thrombin generation. We hypothesize that the expression of FVa via gene therapy can improve hemostasis of both factor IX and FVIII deficiencies, regardless of clotting factor inhibitor. A human FVa (hFVa) expression cassette was constructed, and AAV8 vectors encoding hFVa (AAV8/TTR-hFVa) were intravenously administrated into mice with hemophilia A and B with or without FVIII inhibitors. Hemostasis, including hFVa level, activated partial thromboplastin time (aPTT), tail clip, and the saphenous vein bleeding assay (SVBA), was evaluated. In hemophilia B mice, a dose of 4 × 1013 vg/kg AAV8/TTR-hFVa vectors achieved a complete phenotypic correction over 28 weeks. In hemophilia A mice, hemostasis improvement was also achieved, regardless of FVIII inhibitor development. In vivo hemostasis efficacy was confirmed by tail clip and SVBA. Interestingly, while minimal shortening of aPTT was observed at a lower dose of AAV8 vectors, hemostasis improvement was still achieved via in vivo bleeding assays. Collectively, FVa-based AAV gene therapy shows promise for hemostasis correction in hemophilia, regardless of inhibitor development and no potential risk for thrombosis.
Case report: Eosinophilic pneumonia associated with vedolizumab therapy in a patient with ulcerative colitis
Authors: Zhu Wanwan , Zhao Tianhao , Wei Jun , Chai Damin , Zhao Cancan , Zhu Yu , Deng Min
Published: August 2022

Extraintestinal manifestations are common in patients with inflammatory bowel disease, while respiratory involvement is less common. Vedolizumab is a new class of anti-integrin biological agents approved for treating inflammatory bowel disease. In this report, we present the case of a 38-year-old patient with ulcerative colitis for 7 years who developed cough, fever, and pulmonary infiltrates after taking vedolizumab. There was a spontaneous improvement in clinical symptoms and radiological abnormalities after discontinuing vedolizumab and introducing steroids. Despite the rarity of vedolizumab-induced eosinophilic pneumonia, the case reports indicate that patients with unexplained respiratory symptoms that are taking vedolizumab should be fully contemplated.
The avian gut microbiota: Diversity, influencing factors, and future directions
Authors: Sun Fengfei , Chen Junfeng , Liu Kai , Tang Meizhen , Yang Yuewei
Published: August 2022

The gut microbiota is viewed as the “second genome” of animals, sharing intricate relationships with their respective hosts. Because the gut microbial community and its diversity are affected by many intrinsic and extrinsic factors, studying intestinal microbes has become an important research topic. However, publications are dominated by studies on domestic or captive birds, while research on the composition and response mechanism of environmental changes in the gut microbiota of wild birds remains scarce. Therefore, it is important to understand the co-evolution of host and intestinal bacteria under natural conditions to elucidate the diversity, maintenance mechanisms, and functions of gut microbes in wild birds. Here, the existing knowledge of gut microbiota in captive and wild birds is summarized, along with previous studies on the composition and function, research methods employed, and factors influencing the avian gut microbial communities. Furthermore, research hotspots and directions were also discussed to identify the dynamics of the avian gut microbiota, aiming to contribute to studies of avian microbiology in the future.
The root zone of graminoids: A niche for H2-consuming acetogens in a minerotrophic peatland
Authors: Meier Anja B. , Oppermann Sindy , Drake Harold L. , Schmidt Oliver
Published: August 2022

The importance of acetogens for H2 turnover and overall anaerobic degradation in peatlands remains elusive. In the well-studied minerotrophic peatland fen Schlöppnerbrunnen, H2-consuming acetogens are conceptualized to be largely outcompeted by iron reducers, sulfate reducers, and hydrogenotrophic methanogens in bulk peat soil. However, in root zones of graminoids, fermenters thriving on rhizodeposits and root litter might temporarily provide sufficient H2 for acetogens. In the present study, root-free peat soils from around the roots of Molinia caerulea and Carex rostrata (i.e., two graminoids common in fen Schlöpnnerbrunnen) were anoxically incubated with or without supplemental H2 to simulate conditions of high and low H2 availability in the fen. In unsupplemented soil treatments, H2 concentrations were largely below the detection limit (∼10 ppmV) and possibly too low for acetogens and methanogens, an assumption supported by the finding that neither acetate nor methane substantially accumulated. In the presence of supplemental H2, acetate accumulation exceeded CH4 accumulation in Molinia soil whereas acetate and methane accumulated equally in Carex soil. However, reductant recoveries indicated that initially, additional unknown processes were involved either in H2 consumption or the consumption of acetate produced by H2-consuming acetogens. 16S rRNA and 16S rRNA gene analyses revealed that potential acetogens (Clostridium, Holophagaceae), methanogens (Methanocellales, Methanobacterium), iron reducers (Geobacter), and physiologically uncharacterized phylotypes (Acidobacteria, Actinobacteria, Bacteroidetes) were stimulated by supplemental H2 in soil treatments. Phylotypes closely related to clostridial acetogens were also active in soil-free Molinia and Carex root treatments with or without supplemental H2. Due to pronounced fermentation activities, H2 consumption was less obvious in root treatments, and acetogens likely thrived on root organic carbon and fermentation products (e.g., ethanol) in addition to H2. Collectively, the data highlighted that in fen Schlöppnerbrunnen, acetogens are associated to graminoid roots and inhabit the peat soil around the roots, where they have to compete for H2 with methanogens and iron reducers. Furthermore, the study underscored that the metabolically flexible acetogens do not rely on H2, potentially a key advantage over other H2 consumers under the highly dynamic conditions characteristic for the root-zones of graminoids in peatlands.
Protein stability [determination] problems
Authors: Ahmad Faizan
Published: August 2022

Human health depends on the correct folding of proteins, for misfolding and aggregation lead to diseases. An unfolded (denatured) protein can refold to its original folded state. How does this occur is known as the protein folding problem. One of several related questions to this problem is that how much more stable is the folded state than the unfolded state. There are several measures of protein stability. In this article, protein stability is given a thermodynamic definition and is measured by Gibbs free energy change (ΔGD0) associated with the equilibrium, native (N) conformation ↔ denatured (D) conformation under the physiological condition usually taken as dilute buffer (or water) at 25 °C. We show that this thermodynamic quantity (ΔGD0), where subscript D represents transition between N and D states, and superscript 0 (zero) represents the fact that the transition occurs in the absence of denaturant, can be neither measured nor predicted under physiological conditions. However, ΔGD can be measured in the presence of strong chemical denaturants such as guanidinium chloride and urea which are shown to destroy all noncovalent interactions responsible for maintaining the folded structure. A problem with this measurement is that the estimate of ΔGD0 comes from the analysis of the plot of ΔGDversus denaturant concentration, which requires a long extrapolation of values of ΔGD, and all the three methods of extrapolation give three different values of ΔGD0 for a protein. Thus, our confidence in the authentic value of ΔGD0 is eroded. Another problem with this in vitro measurement of ΔGD0 is that it is done on the pure protein sample in dilute buffer which is a very large extrapolation of the in vivo conditions, for the crowding effect on protein stability is ignored.
Characterizing the role of SLC3A2 in the molecular landscape and immune microenvironment across human tumors
Authors: He Jiajun , Liu Dong , Liu Mei , Tang Rong , Zhang Dongqing
Published: August 2022

Background: Inducing ferroptosis in human tumors has become a potential strategy to improve the prognosis of patients, even in those with chemotherapeutic resistance. The xCT complex is a major target for ferroptosis induction, constituted by SLC7A11 and SLC3A2. The role of SLC7A11 in cancer has been widely studied in recent years. However, related research studies for its partner SLC3A2 are still rare.

Methods: Bulk transcriptome, single-cell sequencing, and immunohistochemical staining were analyzed to explore the expression distribution of SLC3A2. Clinical outcomes were referred to uncover the relationship between SLC3A2 expression and patients’ prognosis. Immune cell infiltration was estimated by multiple deconvolution algorithms. The effect of SLC3A2 on the proliferation and drug resistance of cancer cell lines was evaluated by DEPMAP.

Results: Upregulated SLC3A2 may have an adverse effect on the survival of multiple cancers such as lower-grade glioma and acute myeloid leukemia. SLC3A2 expression is indispensable for multiple cell lines’ proliferation, especially for ESO51 (a cell line for esophageal cancer). In addition, SLC3A2 expression level was related to the remodeling of the immune microenvironment in cancers and some immune checkpoints such as PD-1 and PD-L1, which were potential therapeutic targets in many distinct cancers.

Conclusion: Our study systematically elucidated the role of SLC3A2 in the survival of cancer patients and the potential immunotherapeutic response. Few molecular mechanisms by which SLC3A2 regulates anti-tumor immunity have been clarified in the present study, which is the main limitation. Future research into the biological mechanism could further help with targeted treatment for cancer patients.
Expression of Opsins of the Box Jellyfish Tripedalia cystophora Reveals the First Photopigment in Cnidarian Ocelli and Supports the Presence of Photoisomerases
Authors: Garm Anders , Svaerke Jens-Erik , Pontieri Daniela , Oakley Todd H.
Published: August 2022

Cubomedusae, or box jellyfish, have a complex visual system comprising 24 eyes of four types. Like other cnidarians, their photoreceptor cells are ciliary in morphology, and a range of different techniques together show that at least two of the eye types—the image-forming upper and lower lens eyes—express opsin as the photopigment. The photoreceptors of these two eye types express the same opsin (Tc LEO), which belongs to the cnidarian-specific clade cnidops. Interestingly, molecular work has found a high number of opsin genes in box jellyfish, especially in the Caribbean species Tripedalia cystophora, most of which are of unknown function. In the current study, we raised antibodies against three out of five opsins identified from transcriptomic data from T. cystophora and used them to map the expression patterns. These expression patterns suggest one opsin as the photopigment in the slit eyes and another as a putative photoisomerase found in photoreceptors of all four eyes types. The last antibody stained nerve-like cells in the tentacles, in connection with nematocytes, and the radial nerve, in connection with the gonads. This is the first time photopigment expression has been localized to the outer segments of the photoreceptors in a cnidarian ocellus (simple eye). The potential presence of a photoisomerase could be another interesting convergence between box jellyfish and vertebrate photoreceptors, but it awaits final experimental proof.
Disrupted development from head to tail: Pervasive effects of postnatal restricted resources on neurobiological, behavioral, and morphometric outcomes
Authors: Kent Molly H. , Jacob Joanna C. , Bowen Gabby , Bhalerao Janhavi , Desinor Stephanie , Vavra Dylan , Leserve Danielle , Ott Kelly R. , Angeles Benjamin , Martis Michael , Sciandra Katherine , Gillenwater Katherine , Glory Clark , Meisel Eli , Choe Allison , Olivares-Navarrete Rene , Puetzer Jennifer L. , Lambert Kelly
Published: August 2022

When a maternal rat nurtures her pups, she relies on adequate resources to provide optimal care for her offspring. Accordingly, limited environmental resources may result in atypical maternal care, disrupting various developmental outcomes. In the current study, maternal Long-Evans rats were randomly assigned to either a standard resource (SR) group, provided with four cups of bedding and two paper towels for nesting material or a limited resource (LR) group, provided with a quarter of the bedding and nesting material provided for the SR group. Offspring were monitored at various developmental phases throughout the study. After weaning, pups were housed in same-sex dyads in environments with SRs for continued observations. Subsequent behavioral tests revealed a sex × resource interaction in play behavior on PND 28; specifically, LR reduced play attacks in males while LR increased play attacks in females. A sex × resource interaction was also observed in anxiety-related responses in the open field task with an increase in thigmotaxis in LR females and, in the social interaction task, females exhibited more external rears oriented away from the social target. Focusing on morphological variables, tail length measurements of LR males and females were shorter on PND 9, 16, and 21; however, differences in tail length were no longer present at PND 35. Following the behavioral assessments, animals were perfused at 56 days of age and subsequent immunohistochemical assays indicated increased glucocorticoid receptors in the lateral habenula of LR offspring and higher c-Fos immunoreactivity in the basolateral amygdala of SR offspring. Further, when tail vertebrae and tail tendons were assessed via micro-CT and hydroxyproline assays, results indicated increased trabecular separation, decreased bone volume fraction, and decreased connectivity density in bones, along with reduced collagen concentration in tendons in the LR animals. In sum, although the restricted resources only persisted for a brief duration, the effects appear to be far-reaching and pervasive in this early life stress animal model.
Non-invasive Brain Temperature Measurement in Acute Ischemic Stroke
Authors: Horn MacKenzie , Diprose William K , Pichardo Samuel , Demchuk Andrew , Almekhlafi Mohammed
Published: August 2022

Selective therapeutic hypothermia in the setting of mechanical thrombectomy (MT) is promising to further improve the outcomes of large vessel occlusion stroke. A significant limitation in applying hypothermia in this setting is the lack of real-time non-invasive brain temperature monitoring mechanism. Non-invasive brain temperature monitoring would provide important information regarding the brain temperature changes during cooling, and the factors that might influence any fluctuations. This review aims to provide appraisal of brain temperature changes during stroke, and the currently available non-invasive modalities of brain temperature measurement that have been developed and tested over the past 20 years. We cover modalities including magnetic resonance spectroscopy imaging (MRSI), radiometric thermometry, and microwave radiometry, and the evidence for their accuracy from human and animal studies. We also evaluate the feasibility of using these modalities in the acute stroke setting and potential ways for incorporating brain temperature monitoring in the stroke workflow.
Case report: Meningitis and intracranial aneurysm caused by mixed infection of oral microflora dominated by anaerobes
Authors: Cheng Hongjiang , Xu Lina , Yang Fengbing , Jia Longbin , Zhao Doudou , Li Huimin , Liu Wei , Li Yujuan , Liu Xiaoli , Geng Xia , Guo Jiaying , Ling Chen , Zhang Jing
Published: August 2022

Introduction

Meningitis caused by oral anaerobic bacteria is rare, especially when complicated with an infected intracranial aneurysm. This paper has described an extremely rare case of bacterial meningitis caused by a mixed infection of oral microflora dominated by anaerobes, which developed cerebral infarcts, brain abscess, intracranial aneurysm, and severe hydrocephalus during treatment.

Case report

We describe a 65-year-old male patient who was presented with fever and headache as the initial symptoms and then developed left ophthalmoplegia, right hemiplegia, and disturbance of consciousness. Brain imaging showed that intracranial lesions were increased progressively, and cerebral infarcts, brain abscesses, intracranial aneurysm, and severe hydrocephalus were appeared gradually. Eventually, we diagnosed it as anaerobic meningitis by making deoxyribonucleic acid sequencing from the brain abscess pus. After using an anti-microbial regimen that can sufficiently cover anaerobes, the patient's condition was effectively controlled.

Conclusion

Anaerobic meningitis can cause a series of intracranial complications. Among them, the intracranial aneurysm is extremely rare. When evidence shows that the infection originates from oral flora, physicians should consider the possibility of this type of encephalitis. An early diagnosis and timely treatment are crucial to improving the prognosis.
How do cardiovascular risk factors correlate with post-stroke cognitive function: Directly or indirectly through stroke severity?
Authors: Hua Jianian , Zhou Yixiu , Chen Licong , Tang Xiang , Diao Shanshan , Fang Qi
Published: August 2022

Objectives

Cognitive impairment may affect one-third of stroke survivors. Cardiovascular risk factors and stroke severity were known to be associated with cognitive function after stroke. However, it is unclear whether cardiovascular risk factors directly affect cognition after stroke, indirectly affect cognition by changing stroke severity, or both. Moreover, the effect of a combination of hypertension and diabetes mellitus was conflicting. We aimed to investigate the multiple direct and indirect associations and inspire potential intervention strategies.

Materials and methods

From February 2020 to January 2021, 350 individuals received cognitive tests within 7 days after incident stroke. Cognitive tests were performed using the Chinese version of the Mini-Mental State Examination (MMSE). A moderated mediation model was constructed to test the indirect associations between cardiovascular and demographic risk factors and cognition mediated through stroke severity, the direct associations between risk factors and cognition, and the moderating effects of hypertension and diabetes.

Results

Age (estimate, −0.112), atrial fibrillation (estimate, −4.092), and stroke severity (estimate, −1.994) were directly associated with lower cognitive function after stroke. Vascular disease (estimate, 1.951) and male sex (estimate, 2.502) were directly associated with better cognition after stroke. Higher education level was associated with better cognition directly (estimate, 1.341) and indirectly (estimate, 0.227) through stroke severity. The combination of hypertension decreased the magnitude of the negative association between atrial fibrillation and cognition (estimate, from −4.092 to −3.580).

Conclusion

This is the first Chinese study exploring the moderated and mediating associations between cardiovascular risk factors, stroke severity, and cognitive function after stroke. Age, female sex, and atrial fibrillation were directly associated with lower cognition after stroke. The combination of hypertension might have a positive effect on cognition.
A Novel Therapeutic Approach With Sodium Pyruvate on Vital Signs, Acid–Base, and Metabolic Disturbances in Rats With a Combined Blast and Hemorrhagic Shock
Authors: Saha Biswajit , Sahu Geetaram , Sharma Pushpa
Published: August 2022

Background

Blast injuries from improvised explosive devices (IEDs) are known to cause blast traumatic brain injuries (bTBIs), hemorrhagic shock (HS), organ damage, mitochondrial dysfunction, and subsequent free radical production. A pre-citric acid cycle reagent, pyruvate, is suggested to improve mitochondrial ATP production through the activation of the mitochondrial gatekeeper enzyme “pyruvate dehydrogenase complex (PDH).” Our study aimed to investigate the role of physiologic, metabolic, and mitochondrial effects of hypertonic sodium pyruvate resuscitation in rats with a combined blast and HS injury.

Methods

A pre-clinical rat model of combined injury with repetitive 20 PSI blast exposure accompanied with HS and fluid resuscitation (sodium pyruvate as metabolic adjuvant or hypertonic saline as control), followed by transfusion of shed blood was used in this study. Control sham animals (instrumental and time-matched) received anesthesia and cannulation, but neither received any injury nor treatment. The mean arterial pressure and heart rate were recorded throughout the experiment by a computerized program. Blood collected at T0 (baseline), T60 (after HS), and T180 (end) was analyzed for blood chemistry and mitochondrial PDH enzyme activity.

Results

Sodium pyruvate resuscitation significantly improved the mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), hemodynamic stability (Shock index), and autonomic response (Kerdo index) after the HS and/or blast injury. Compared with the baseline values, plasma lactate and lactate/pyruvate ratios were significantly increased. In contrast, base excess BE/(HCO3-) was low and the pH was also acidotic <7.3, indicating the sign of metabolic acidosis after blast and HS in all animal groups. Sodium pyruvate infusion significantly corrected these parameters at the end of the experiment. The PDH activity also improved after the sodium pyruvate infusion.

Conclusion

In our rat model of a combined blast and HS injury, hypertonic sodium pyruvate resuscitation was significantly effective in hemodynamic stabilization by correcting the acid–base status and mitochondrial mechanisms via its pyruvate dehydrogenase enzyme.
Association between serum calcium levels and first stroke: A community-based nested case-control study
Authors: Ding Congcong , Bi Chonglei , Lin Tengfei , Liu Lishun , Song Yun , Wang Binyan , Wang Ping , Fang Chongqian , Ma Hai , Huang Xiao , Xu Xiping , Zhang Hao , Hu Lihua , Huo Yong , Wang Xiaobin , Bao Huihui , Cheng Xiaoshu
Published: August 2022

Background

Evidence from epidemiologic studies has been limited and inconsistent regarding the role of serum calcium in stroke incidence risk. We aimed to evaluate the association between serum albumin-corrected calcium and the risk of the first stroke in the Chinese community-dwelling population.

Methods

The study sample population was drawn from the “H-type Hypertension and Stroke Prevention and Control Project.” Using a nested case-control study, a total of 1,255 first-stroke cases and 1,255 controls matched for age, sex, and village were included in the final data analysis. We measured the serum calcium by inductively coupled plasma mass spectrometry and assessed the associations between serum albumin-corrected calcium and first stroke using conditional logistic regression.

Results

The overall mean (SD) serum albumin-corrected calcium was 8.9 (0.6) mg/dl. Compared with the middle tertile (8.7–9.1 mg/dl), the multivariate-adjusted odds ratios (95% CIs) of first total stroke associated with the lowest tertile and the highest tertile of serum albumin-corrected calcium were 1.37 (1.10, 1.70) and 1.30 (1.04, 1.62), respectively. Similar trends were observed for the first ischemic stroke. Consistently, restricted cubic spline showed a U-shaped association between serum albumin-corrected calcium and risk of total stroke and ischemic stroke. However, serum albumin-corrected calcium had no significant effect on first hemorrhagic stroke. No significant effect modification was observed in the subgroup analysis.

Conclusions

Our results suggested a U-shaped association between serum calcium and first stroke; both low and high serum calcium levels were associated with an increased risk of the first stroke in the Chinese population.
Application of DTI and fMRI in moyamoya disease
Authors: Hao Xiaokuan , Liu Ziqi , He Shihao , Wang Yanru , Zhao Yuanli , Wang Rong
Published: August 2022

Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) are used to detect the microstructure of white matter and the function of gray matter, respectively. The damage of these structures will lead to the change of cognitive level in patients with moyamoya disease. In this paper, the principles of DTI and fMRI, their applications and challenges in moyamoya disease are reviewed.