bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic analysis of synaptonemal complex dynamics during meiosis of yeast Saccharomyces cerevisiae reveals biphasic growth and abortive disassembly
Authors: Pollard Michael G. , Rockmill Beth , Oke Ashwini , Anderson Carol M. , Fung Jennifer C.
Published: February 2023

The synaptonemal complex (SC) is a dynamic structure formed between chromosomes during meiosis which stabilizes and supports many essential meiotic processes such as pairing and recombination. In budding yeast, Zip1 is a functionally conserved element of the SC that is important for synapsis. Here, we directly measure the kinetics of Zip1-GFP assembly and disassembly in live cells of the yeast S. cerevisiae. The imaging of SC assembly in yeast is challenging due to the large number of chromosomes packed into a small nucleus. We employ a zip3Δ mutant in which only a few chromosomes undergo synapsis at any given time, initiating from a single site on each chromosome, thus allowing the assembly and disassembly kinetics of single SCs to be accurately monitored in living cells. SC assembly occurs with both monophasic and biphasic kinetics, in contrast to the strictly monophasic assembly seen in C. elegans. In wild-type cells, once maximal synapsis is achieved, programmed final disassembly rapidly follows, as Zip1 protein is actively degraded. In zip3Δ, this period is extended and final disassembly is prolonged. Besides final disassembly, we found novel disassembly events involving mostly short SCs that disappeared in advance of programmed final disassembly, which we termed “abortive disassembly.” Abortive disassembly is distinct from final disassembly in that it occurs when Zip1 protein levels are still high, and exhibits a much slower rate of disassembly, suggesting a different mechanism for removal in the two types of disassembly. We speculate that abortive disassembly events represent defective or stalled SCs, possibly representing SC formation between non-homologs, that is then targeted for dissolution. These results reveal novel aspects of SC assembly and disassembly, potentially providing evidence of additional regulatory pathways controlling not just the assembly, but also the disassembly, of this complex cellular structure.
The progress of research on the application of redox nanomaterials in disease therapy
Authors: Shi Xiaolu , Tian Ye , Zhai Shaobo , Liu Yang , Chu Shunli , Xiong Zhengrong
Published: February 2023

Redox imbalance can trigger cell dysfunction and damage and plays a vital role in the origin and progression of many diseases. Maintaining the balance between oxidants and antioxidants in vivo is a complicated and arduous task, leading to ongoing research into the construction of redox nanomaterials. Nanodrug platforms with redox characteristics can not only reduce the adverse effects of oxidative stress on tissues by removing excess oxidants from the body but also have multienzyme-like activity, which can play a cytotoxic role in tumor tissues through the catalytic oxidation of their substrates to produce harmful reactive oxygen species such as hydroxyl radicals. In this review, various redox nanomaterials currently used in disease therapy are discussed, emphasizing the treatment methods and their applications in tumors and other human tissues. Finally, the limitations of the current clinical application of redox nanomaterials are considered.
Gut microbiome and mycobiome in inflammatory bowel disease patients with Clostridioides difficile infection
Authors: Yu Si , Ge Xiaomeng , Xu Hui , Tan Bei , Tian Bowen , Shi Yujie , Dai Yimin , Li Yue , Hu Songnian , Qian Jiaming
Published: February 2023

Background

Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD) and has been reported as a risk factor for poor outcome. However, gut microbiome and mycobiome of IBD patients with CDI have been barely investigated. This study aimed to assess the gut microbiome and mycobiome in IBD patients with CDI.

Methods

We collected fecal samples from patients with active IBD and concomitant CDI (IBD-CDI group, n=25), patients with active IBD and no CDI (IBD-only group, n=51), and healthy subjects (HC, n=40). Patients’ characteristics including demographic data, disease severity, and medication history were collected. Metagenomic sequencing, taxonomic and functional analysis were carried out in the samples.

Results

We found that the bacterial alpha diversity of the IBD-CDI group was decreased. The bacterial and fungal beta diversity variations between IBD patients and HC were significant, regardless of CDI status. But the IBD-CDI group did not significantly cluster separately from the IBD-only group. Several bacterial taxa, including Enterococcus faecium, Ruminococcus gnavus, and Clostridium innocuum were overrepresented in the IBD-CDI group. Furthermore, IBD patients with CDI were distinguished by several fungal taxa, including overrepresentation of Saccharomyces cerevisiae. We also identified functional differences in IBD patients with CDI include enrichment of peptidoglycan biosynthesis. The network analysis indicated specific interactions between microbial markers in IBD-CDI patients.

Conclusion

IBD patients with CDI had pronounced microbial dysbiosis. Gut micro-ecological changes in IBD patients with CDI might provide insight into the pathological process and potential strategies for diagnosis and treatment in this subset of patients.
Measures for explainable AI: Explanation goodness, user satisfaction, mental models, curiosity, trust, and human-AI performance
Authors: Hoffman Robert R. , Mueller Shane T. , Klein Gary , Litman Jordan
Published: February 2023

If a user is presented an AI system that portends to explain how it works, how do we know whether the explanation works and the user has achieved a pragmatic understanding of the AI? This question entails some key concepts of measurement such as explanation goodness and trust. We present methods for enabling developers and researchers to: (1) Assess thea priorigoodness of explanations, (2) Assess users' satisfaction with explanations, (3) Reveal user's mental model of an AI system, (4) Assess user's curiosity or need for explanations, (5) Assess whether the user's trust and reliance on the AI are appropriate, and finally, (6) Assess how the human-XAI work system performs. The methods we present derive from our integration of extensive research literatures and our own psychometric evaluations. We point to the previous research that led to the measurement scales which we aggregated and tailored specifically for the XAI context. Scales are presented in sufficient detail to enable their use by XAI researchers. For Mental Model assessment and Work System Performance, XAI researchers have choices. We point to a number of methods, expressed in terms of methods' strengths and weaknesses, and pertinent measurement issues.
Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing
Authors: Rozenbaum Zach , Granot Yoav , Sadeh Ben , Havakuk Ofer , Arnold Joshua H. , Shimiaie Jason , Ghermezi Michael , Barak Orly , Ben Gal Yanai , Shacham Yacov , Keren Gad , Topilsky Yan , Laufer-Perl Michal
Published: February 2023

Background

We aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET).

Methods

Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex.

Results

One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction).

Conclusions

Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.
Early Cretaceous volcanic-arc magmatism in the Dalat-Kratie Fold Belt of eastern Cambodia: implications for the lithotectonic evolution of the Indochina terrane
Authors: Shellnutt J. Gregory , Ma George S.-K. , Chan Jacky S.-L. , Wong Jean P.-M. , Wang Kuo-Lung
Published: February 2023

Mesozoic granitic plutons are found throughout the Indochina terrane of eastern Cambodia and southern Vietnam. The granitic rocks range in age from Early Triassic (240 Ma) to Late Cretaceous (80 Ma) and record distinct tectonomagmatic periods associated with subduction of the Paleotethys and Paleo-Pacific oceans. Samples collected from the Snoul pluton, eastern Cambodia are composed of silicic and intermediate dioritic rocks, and basalt. The quartz diorites and diorites are magnesian, metaluminous, calcic to calc-alkalic, and similar to volcanic-arc granitoids whereas the basaltic rocks are compositionally similar to within-plate basalt. Zircon U-Pb geochronology and Lu-Hf isotopes and whole rock Sr-Nd isotopes show that the silicic rocks are Albian and isotopically juvenile (107.5 ± 0.3 Ma, 109.1 ± 0.4 Ma; εHf(t) = +7.0–+17.0; 87Sr/86Sri = 0.704313–0.707681; εNd(t) = +3.1–+4.9). Fractional crystallization modeling using a dioritic composition as the parental magma demonstrates that it is possible to generate the quartz diorite compositions under oxidizing (ΔFMQ +1) and hydrous (H2O = 2 wt%) conditions suggesting that they are consanguineous. The isotopically juvenile nature of the dioritic rocks and their compositional similarity (SiO2 ≥ 56 wt%, Al2O3 ≥ 15 wt%, Sr ≥ 400 ppm, Y ≤ 18 ppm, Yb ≤ 1.9 ppm) to adakitic rocks indicates that the parental magmas of the Snoul pluton were likely derived by partial melting of juvenile mafic basement rocks of the Indochina terrane. Moreover, Early Cretaceous plutonic rocks of Cambodia are isotopically distinct from plutonic rocks of similar age and tectonic setting from Vietnam suggesting that there could be a lithotectonic domain boundary within the Southern Indochina terrane. In contrast, the basaltic rocks likely record a temporally distinct period of magmatism associated with Late Cenozoic tensional plate stress.
Mechanical test and action mechanism of interface between gravel soil and concrete
Authors: Du Peng , Zhou Dequan , Liu Xiaoling , Chen Xin
Published: February 2023

The mechanical properties of the gravel soil-concrete structure interface are one of the important issues in academia and engineering. In this research, gravel soil samples were collected from the Three Gorges Reservoir region to carry out simple shear and direct shear tests of the gravel soil-structure interface. The shearing process was simulated with the numerical method. The strength and deformation characteristics of the interface, the applicability of the interface constitutive model, and the failure mechanism of the interface were analyzed. The results show that: 1) The direct shear test curve of the gravel soil-concrete interface shows strain softening with obvious stress peak, while the simple shear test curve shows strain hardening. The stress peak of the direct shear test is about 30% higher than that of the simple shear test. The shear contraction effect of the simple shear test is about 31% larger than that of the direct shear test. 2) The non-linear relationship of the gravel soil-concrete interface can be described by a hyperbola model, which has a good adaptability to the constitutive relationship of the interface in numerical analysis software. 3) The gravel soil-concrete interface gradually develops shear failure from the edge to the inside. The essence of soil-structure interaction is the movement of soil grains. The research results can provide a reference for the analysis of gravel soil-concrete interaction.
Research on the impact of green finance development on energy intensity in China
Authors: An Qiguang , Lin Chengwei , Li Qingzhao , Zheng Lin
Published: February 2023

China has accelerated its energy transition to help achieve carbon peaking and neutrality. This resulted in significant investment and financial demand, and green finance has developed into a potent tool to support energy transition. This study used Chinese provincial panel data from 2007 to 2019 and investigated the effects of green finance development on energy intensity based on the mediating effect model, threshold model, and spatial Durbin model. The findings indicate that green finance development significantly lowers energy intensity, in which industrial structure upgrading plays a mediating role. Based on the threshold effect, when the green finance index rises above 0.199, the effect of reducing energy intensity becomes significant and exhibits a nonlinear feature of diminishing marginal effect. By examining the spatial spillover effect, the analysis shows that the development of green finance not only reduces the energy intensity of the region but also reduces the energy intensity of neighboring regions. Based on these findings, we proposed regionally targeted and differentiated green finance development policies to reduce energy intensity as soon as possible and assist in reaching carbon neutrality.
Hypothyroidism: The difficulty in attributing symptoms to their underlying cause
Authors: Jansen Heleen I. , Boelen Anita , Heijboer Annemieke C. , Bruinstroop Eveline , Fliers Eric
Published: February 2023

Common symptoms of overt hypothyroidism are non-specific and include fatigue, lethargy, and dry skin. Although the diagnosis is considered to be straightforward, no single symptom can be used to identify patients with overt hypothyroidism, while many patients with subclinical hypothyroidism are asymptomatic. A large population-based study on the spectrum of symptoms in subclinical hypothyroidism showed similar rates of thyroid disease-related symptoms compared with euthyroid subjects, while the TSH concentration had no impact on symptom score. Together, these findings make it challenging to attribute symptoms to their underlying cause. This is also true in the case of unexplained persistent symptoms in levothyroxine-treated patients. Although generally considered a life-long replacement therapy, successful thyroid hormone discontinuation resulting in euthyroidism has been reported in approximately one third of patients. Thus, we overtreat patients with (subclinical) hypothyroidism, highlighting the importance of reliable diagnostic criteria. The diagnostic process, including the implementation of robust TSH and FT4 reference intervals, is especially challenging in specific situations including aging, pregnancy, non-thyroidal illness, and central hypothyroidism. There is a clear need for improved adherence to current guidelines from scientific societies and for willingness to manage symptoms without a clear pathological correlate, especially in the case of mild TSH elevations. This review will highlight recent literature on this topic and offers some practice points.
Techno-economic analysis of the transition toward the energy self-sufficiency community based on virtual power plant
Authors: Wang Yafei , Gao Weijun , Li You , Qian Fanyue , Yao Wanxiang
Published: February 2023

Distributed energy resources are important measures to increase energy self-sufficiency and overcome the global carbon reduction problem. However, individual planned renewable energy generation poses a significant threat to the power grid. Therefore, virtual power plant (VPP) is attracting considerable attention as a means of aggregating distributed energy in urban areas. This study proposed a VPP model consisting of updating high-efficiency appliances and photovoltaic and energy storage systems. A comprehensive analysis for assessing the technical, economic, and environmental benefits derived from the VPP was presented, indicating the feasibility of a smart community to achieve power self-sufficiency with the support of the VPP. A smart community in Japan was selected as the research object, with a peak power demand of 57,350 kW. The VPP’s load leveling performance, return on investment (ROI), and CO2 emission reduction were analyzed. In addition, external factors, such as electricity price changes and FiT policies, are considered to assess the impact on the economics of the VPP. The results show that the introduction of the VPP system in the community can effectively stabilize the grid load with a peak shaving rate reaching 42.55% and improve the energy self-sufficiency rate of the region reached 100%, besides providing superior economic and environmental benefits (16.26% CO2 emission reduction) on the demand side. Furthermore, the economic performance of VPP shows a good prospect with the fall in equipment prices and the future trend of carbon tax growth. This study provides important insights into the development of VPP in other countries, especially for low-energy self-sufficiency regions.
Multi-time scale stochastic production simulation under VHVDC long-term contract trading electricity quantity constraint
Authors: Hao Lili , Zheng Cheng , Cai Jilin , Lv Xiaoxu , Chen Hao , Shao Yijun
Published: February 2023

A two-layer multi-time scale stochastic production simulation framework is constructed to account for the long-term contract electricity quantity of ultra-high voltage direct current (UHVDC) transmission. On the upper layer, based on the characteristics of load demand and renewable energy output extracted from the historical operating data, monthly and daily production simulation models are carried out considering the seasonal characteristics of hydropower during a high-water period and low-water period to optimize the distribution of contract electric quantity sending through UHVDC transmission in the target year or month. According to the DC transmission electric quantity optimized by the daily production simulation in the upper layer, together with the forecast scenario, the lower layer of the framework provides the optimization of day-ahead scheduling and intra-day rolling dispatch in the implementation process. The day-ahead dispatch optimization makes full use of the adjustment capability of transmission and optimizes the DC transmission electric quantity correction. Its compensation is based on the result of the daily production simulation, then the correction will be returned to the upper layer to restart the optimization of the remaining UHVDC contract electric quantity of the subsequent period and its distribution plan. Combined with the day-ahead DC transmission plan, the intra-day rolling optimization is carried out to adjust the output of the unit using more accurate forecasting scenarios. The distributionally robust optimization model is used in the lower layer to convert an uncertain problem into a deterministic quadratically constrained quadratic programming (QCQP) problem according to the form of an uncertain distribution set. Then the QCQP problem is further converted into a linear programming (LP) problem by using the reformulation linearization technique (RLT). A test system with the energy composition and distribution referring to a real provincial power grid in northwest China is established for verification. The results show that the proposed method can effectively improve the economics of system operation and the accommodation of renewable energy based on ensuring security.
Characterization of 35 Masson pine (Pinus massoniana) half-sib families from two provinces based on metabolite properties
Authors: Quan Wenxuan , Zhao Xizhou , Zhao Chao , Duan Honglang , Ding Guijie
Published: February 2023

Plant metabolism is an important functional trait, and its metabolites have physiological and ecological functions to adapt to the growth environment. However, the physiological and ecological functions of metabolites from different provinces of the same plant species are still unclear. Therefore, this study aimed to determine whether metabolites from different provinces of Masson pine (Pinus massoniana Lamb.) have the corresponding metabolic traits. The gas chromatography–mass spectrometry technique and metabonomic analysis methods were used to characterize 35 Masson pine half-sib families from two provinces. A total of 116 metabolites were putatively identified in 35 families of Masson pine, among which the average content of organic acids was the highest, followed by saccharides and alcohols, and phosphoric acids. Comparative analysis of metabolite groups showed that organic acids, amines, and others were significantly different between the Masson pine families from Guangxi and Guizhou provinces. Six differential metabolites were found between the provinces from Guizhou and Guangxi, namely caffeic acid, L-ascorbic acid, gentiobiose, xylitol, d-pinitol, and β-sitosterol. The most significantly enriched pathways among differentially expressed metabolites between the two provinces were steroid biosynthesis, phenylpropanoid biosynthesis, glutathione metabolism, pentose and glucuronate interconversions. Overall, the results showed that Masson pine half-sib families from different geographical provinces have different metabolite profiles and their metabolites are affected by geographical provenance and growth environment adaptability. This study revealed that the breeding of Masson pine families from different provinces changed the metabolite profiles, providing a reference for the multipurpose breeding of Masson pine.
Characterization of early myocardial inflammation in ischemia-reperfusion injury
Authors: Wu Qihong , Xu Rong , Zhang Kun , Sun Ran , Yang Mengxi , Li Kuan , Liu Hanrui , Xue Yiyuan , Xu Huayan , Guo Yingkun
Published: February 2023

Background

Myocardial injury may be caused by myocardial ischemia-reperfusion (IR), and salvaging such an injury is still a great challenge in clinical practice. This study comprehensively characterized the physiopathologic changes of myocardial injury after IR to explore the underlying mechanism in the early reperfusion phase with particular emphasis on early myocardial inflammation.

Methods and Results

The experimental IR model was obtained by the left anterior descending artery’s transient ligation of C57BL/6 mice. T2W signals of all mice showed increased signal at different IR stages. It was positively correlated with inflammatory cytokines and cells. T2W imaging by 7.0 T MRI surprisingly detected signal enhancement, but histopathology and flow cytometry did not reveal any inflammatory cells infiltration within 3 h after IR. Cardiomyocyte swelling and increased vascular permeability were observed by WGA staining and ultrastructural analysis, respectively. The 3 h IR group showed that the cardiomyocytes were severely affected with disintegrating myofilaments and mitochondria. Both VEGF and phosphorylated Src protein were markedly expressed in the 3 h IR group in comparison with the sham group, and TUNEL staining displayed little positive cells. Cleaved caspase-3 apoptin also has similar expression levels with that of the sham group. Resident macrophages had notably become M1 phenotype. The T2W signal was still elevated, and we observed that collagen deposition occurred from 1 to 7 days.

Conclusions

The inflammation response during the first week after reperfusion injury gradually increase 3 h later, but the main manifestation before that was edema. This study indicated that the first 3 h may be crucial to the early rescue process for reperfusion-induced myocardial injury due to inflammatory cell infiltration absence and apoptosis.
Humoral and Cellular Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients with Multiple Sclerosis: An Israeli Multi-Center Experience Following 3 Vaccine Doses
Authors: Milo Ron , Staun-Ram Elsebeth , Karussis Dimitrios , Karni Arnon , Hellmann Mark A. , Bar-Haim Erez , Miller Ariel ,   The Israeli Neuroimmunology Study Group on COVID-19 Vaccination in Multiple Sclerosis
Published: February 2023

Background

Immunomodulatory/immunosuppressive activity of multiple sclerosis (MS) disease modifying therapies (DMTs) might affect immune responses to SARS-CoV-2 exposure or vaccination in patients with MS (PwMS). We evaluated the effect of DMTs on humoral and cell-mediated immune responses to 2 and 3 vaccinations and the longevity of SARS-Cov-2 IgG levels in PwMS.

Methods

522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, or recovering from COVID-19, were recruited in a nation-wide multi-center study. Blood was collected at 3 time-points: 2-16 weeks and ~6 months post 2nd vaccination and 1-16 weeks following 3rd vaccination. Serological responses were measured by quantifying IgG levels against the spike-receptor-binding-domain of SARS-CoV-2, and cellular responses (in a subgroup analysis) by quantifying IFNγ secretion in blood incubated with COVID-19 spike-antigen.

Results

75% PwMS were seropositive post 2nd or 3rd vaccination. IgG levels decreased by 82% within 6 months from vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2nd vaccination (p=0.025). Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. Similarly, in COVID-19-recovered patients only 54% of ocrelizumab-treated, 75% of fingolimod-treated and 67% of cladribine-treated patients were seropositive. A time interval of ≥5 months between ocrelizumab infusion and vaccination was associated with higher IgG levels (p=0.039 post-2nd vaccination; p=0.036 post-3rd vaccination), and with higher proportions of seropositive patients. Most fingolimod- and ocrelizumab-treated patients responded similarly to 2nd and 3rd vaccination. IFNγ-T-cell responses were detected in 89% and 63% of PwMS post 2nd and 3rd vaccination, however in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively.

Conclusion

PwMS treated with most DMTs developed humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations. Fingolimod- or ocrelizumab-treated patients had diminished humoral responses, and fingolimod compromised the cellular responses, with no improvement after a 3rd booster. Vaccination following >5 months since ocrelizumab infusion was associated with better sero-positivity. These findings may contribute to the development of treatment-stratified vaccination guidelines for PwMS.
Construction and validation of a cuproptosis-related prognostic model for glioblastoma
Authors: Zhang Bohong , Xie Lin , Liu Jiahao , Liu Anmin , He Mingliang
Published: February 2023

Background

Cuproptosis, a newly reported type of programmed cell death, takes part in the regulation of tumor progression, treatment response, and prognosis. But the specific effect of cuproptosis-related genes (CRGs) on glioblastoma (GBM) is still unclear.

Methods

The transcriptome data and corresponding clinical data of GBM samples were downloaded from the TCGA and GEO databases. R software and R packages were used to perform statistical analysis, consensus cluster analysis, survival analysis, Cox regression analysis, Lasso regression analysis, and tumor microenvironment analysis. The mRNA and protein expression levels of model-related genes were detected by RT-qPCR and Western blot assays, respectively.

Results

The expression profile of CRGs in 209 GBM samples from two separate datasets was obtained. Two cuproptosis subtypes, CRGcluster A and CRGcluster B, were identified by consensus cluster analysis. There were apparent differences in prognosis, tumor microenvironment, and immune checkpoint expression levels between the two subtypes, and there were 79 prognostic differentially expressed genes (DEGs). According to the prognostic DEGs, two gene subtypes, geneCluster A and geneCluster B, were identified, and a prognostic risk score model was constructed and validated. This model consists of five prognostic DEGs, including PDIA4, DUSP6, PTPRN, PILRB, and CBLN1. Ultimately, to improve the applicability of the model, a nomogram was established. Patients with GBM in the low-risk cluster have a higher mutation burden and predict a longer OS than in the high-risk group. Moreover, the risk score was related to drug sensitivity and negatively correlated with the CSC index.

Conclusion

We successfully constructed a cuproptosis-related prognostic model, which can independently predict the prognosis of GBM patients. These results further complement the understanding of cuproptosis and provide new theoretical support for developing a more effective treatment strategy.
Estrogen-related genes influence immune cell infiltration and immunotherapy response in Hepatocellular Carcinoma
Authors: Gao Biao , Wang Yafei , Li Chonghui , Lu Shichun
Published: February 2023

Background

Immunotherapy has been the first-line treatment option in advanced Hepatocellular Carcinoma(HCC); but now, there are no established molecular markers that can predict immunotherapy response. Estrogen has a crucial role in the development of a variety of liver illnesses, including liver fibrosis, Nonalcoholic fatty liver disease (NAFLD), and HCC. Nonetheless, the significance of estrogen-related genes in HCC immunotherapy and the underlying molecular mechanisms are not yet fully understood.

Method

In this study, we constructed a novel estrogen-related gene prognostic signature (ERGPS) by analyzing bulk RNA sequencing data from 365 HCC patients. Based on the median risk score, we divided 365 HCC patients into low- and high-risk groups. Tumor mutation burden (TMB), Microsatellite instability (MSI), T cell receptor (TCR) richness, B cell receptor (BCR) richness, single-nucleotide variants (SNV) Neoantigens, Cancer Testicular Antigens (CTA) scores, and Tumour Immune Dysfunction and Exclusion (TIDE) scores were used to evaluate the magnitude of immunotherapy response. Multiple external datasets validate the validity and robustness of the prognostic signature. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate estrogen-related gene overexpression in HCC tissue samples.

Results

ERGPS is an independent risk factor affecting the prognosis of HCC patients and is superior to other clinical variables in predicting patient survival and immunotherapy response. Multiple independent external datasets confirmed the superior predictive efficacy of the prognostic signature. The prognostic signature was positively correlated with TMB score, MSI score, TCR richness, BCR richness, SNV Neoantigens score, CTA score, expression levels of immune checkpoint-related genes, and TIDE score. Patients with HCC in the high-risk group identified by the prognostic signature were likely to be more responsive to immunotherapy and more suitable for immunotherapy. qRT-PCR confirmed that estrogen-related genes of the construct signature were highly expressed in HCC tumor tissues.

Conclusion

Estrogen-related genes are overexpressed in HCC tissues. Our novel prognostic signature can accurately predict not only the prognosis but also the immunotherapy response of HCC patients. In the future, prognostic signatures will be a useful tool for clinicians to screen patients with HCC who are suitable for immunotherapy.
Single-cell RNA datasets and bulk RNA datasets analysis demonstrated C1Q+ tumor-associated macrophage as a major and antitumor immune cell population in osteosarcoma
Authors: Tu Jihao , Wang Duo , Zheng XiaoTian , Liu Bin
Published: February 2023

Background

Osteosarcoma is the most frequent primary bone tumor with a poor prognosis. Immune infiltration proved to have a strong impact on prognosis. We analyzed single-cell datasets and bulk datasets to confirm the main immune cell populations and their properties in osteosarcoma.

Methods

The examples in bulk datasets GSE21257 and GSE32981 from the Gene Expression Omnibus database were divided into two immune infiltration level groups, and 34 differentially expressed genes were spotted. Then, we located these genes among nine major cell clusters and their subclusters identified from 99,668 individual cells in single-cell dataset GSE152048 including 11 osteosarcoma patients. Especially, the markers of all kinds of myeloid cells identified in single-cell dataset GSE152048 were set to gene ontology enrichment. We clustered the osteosarcoma samples in the TARGET-OS from the Therapeutically Applicable Research to Generate Effective Treatments dataset into two groups by complete component 1q positive macrophage markers and compared their survival.

Results

Compared with the low-immune infiltrated group, the high-immune infiltrated group showed a better prognosis. Almost all the 34 differentially expressed genes expressed higher or exclusively among myeloid cells. A group of complete component 1q-positive macrophages was identified from the myeloid cells. In the bulk dataset TARGET-OS, these markers and the infiltration of complete component 1q-positive macrophages related to longer survival.

Conclusions

Complete component 1q-positive tumor-associated macrophages were the major immune cell population in osteosarcoma, which contributed to a better prognosis.
Operationalising ODEMM risk assessment for Integrated Ecosystem Assessment scoping: Complexity vs. manageability
Authors: Pedreschi Debbi , Niiranen Susa , Skern-Mauritzen Mette , Reid David G.
Published: February 2023

Integrated Ecosystem Assessments (IEA) require consideration of the full suite of pressures and impacts affecting ecosystems. However, capacity limitations often severely limit our ability to do everything that we want or ‘should’ do, outside of short-term fully-funded focused research projects. In order to make IEA a reality in many contexts, priority consideration has to be given to how to achieve such comprehensive assessments. Ecoregions and Large Marine Ecosystems (LMEs) have been identified as potential management units, however these large areas encompass diverse habitats, and multiple nations with diverse human communities and use of marine environments, and a multitude of different management strategies. In this context, how can we make IEA an operational tool that can be applied at such high-level in a comparable, yet regionally-relevant adaptable approach? This paper outlines the demonstration and adaptation of an established risk assessment approach (Options for Delivering Ecosystem-Based Marine Management: ODEMM) to a rapid risk scoping tool, and how this approach has been applied using open source common analytical tools to improve operationality in both the Mission Atlantic project and the International Council for the Exploration of the Seas (ICES) Integrated Ecosystem Assessment Working Groups. Furthermore, a hierarchical approach is detailed that allows the integration of different levels of detail into a common format. The resulting assessments are then ground-truthed with stakeholders to identify issues, omissions, potential conflicts, and key areas of interest for the next steps of the IEA process.
Strong hydrodynamic processes observed in the Mediterranean Cassidaigne submarine canyon
Authors: Brun Lénaïg , Pairaud Ivane , Jacinto Ricardo Silva , Garreau Pierre , Dennielou Bernard
Published: February 2023

Introduction

Submarine canyons are incisive morphologies that play an important role in the exchange between shallow and deep waters. They interact with the general circulation and induce a specific circulation locally oriented by the morphology. The characteristics of the physical processes at play, the way they interact with each other and the influence of extreme events is still an open question as few observations are available. To answer this question and to improve the representation of submarine canyons in numerical models, it is key to understand the specific circulation patterns and their transitions in these specific environments.

Methods

This paper presents observations of currents, temperature and turbidity along the Cassidaigne canyon, northwestern Mediterranean Sea. Two oceanographic cruises carried out in 2017 and 2019 gathered data from the outer shelf and canyon head at 100-400 m depth to the base of the continental slope at 1900 m depth.

Results and Discussion

The circulation in the Cassidaigne area is subject to upwelling and downwelling-favorable winds, to the Northern Current and its associated mesoscale structures and is oriented by the local morphology. Upwellings occur both during stratified and non-stratified conditions. They are triggered by a wind forcing higher than 14 m s–1 and their consecutive relaxations are marked by a counter-current. Near the canyon head and on the shelf, the current orientation depends on the stratification, the wind, the bottom morphology and the general circulation. The mesoscale variability of the Northern Current can lead to its intrusion over the shelf leading to barotropic cross currents over the canyon. At 1700 m depth, a quasi-permanent residual up-canyon flow is observed in a narrow gorge area and can be extrapolated to the canyon body. Finally, turbidity currents were observed for the first time in connection with upwelling events, suggesting the key role of canyons’ internal hydrodynamics on shelf sedimentary processes.
Seasonal variability of satellite-derived primary production in the South China Sea from an absorption-based model
Authors: Lv Hang , Wang Guifen , Xu Wenlong , Zhang Yinxue , Jiang Long
Published: February 2023

Seasonal patterns of marine net primary production (NPP) are crucial for understanding the marine ecosystem and biogeochemical cycles. Uncoupling of seasonal variations between NPP and phytoplankton chlorophyll-a over different areas has attracted much attention. In this study, following a review of previous studies, monthly climatological NPP data from 2003 to 2020, estimated using the Size-fractioned Phytoplankton Pigment Absorption (aph)-based NPP Model (SABPM), were selected to study the seasonal variability of NPP in the South China Sea (SCS). Results showed the spatial differences of NPP seasonality and its departures from climatology in extreme El Niño-Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD) years. Cluster analysis for climatological monthly data identified significant differences of NPP seasonality in five typical regions. In coastal regions along the northern SCS and off eastern Vietnam, NPP exhibited the most obvious seasonal cycle with maximum (minimum) values in summer (winter), attributable mainly to river discharge and summer upwelling. In regions off northwestern Luzon and coast of southern SCS, NPP showed peaks in winter, which were related to strong mixing and upwelling. In northwestern SCS, NPP was high during May–September in phase with sea surface temperature and the primary controlling factors were found to be shallow nutricline depth and wind-driven mixing. Owing to the deep nutricline depth in the central basin, NPP exhibited little seasonal variability; only a weak signal was observed in spring in phase with photosynthetically active radiation. Local dynamics on regulating the nutrient supply and light availability contribute to these regional differences in NPP seasonality, which could also be affected by extreme climate events. The largest anomalies of the NPP seasonal cycle coincide with 2015/2016 ENSO and super IOD in 2020. During these events, enhanced (weakened) westerly winds caused fall (rise) of SLA and increase (decrease) of NPP in coastal regions along the northern SCS and that off eastern Vietnam. Overall, theaph-based model shows a new perspective to study the spatiotemporal variations of NPP in the SCS.
Numerical study of sediment suspension affected by rigid cylinders under unidirectional and combined wave–current flows
Authors: Lou Sha , Chen Xiaolan , Zhou Shengyu , Ma Gangfeng , Liu Shuguang , Radnaeva Larisa Dorzhievna , Nikitina Elena , Fedorova Irina Viktorovna
Published: February 2023

Sediment transport modeling for flows with cylinders is very challenging owing to the complicated flow–cylinder–sediment interactions, especially under the combined wave-current flows. In this paper, an improved formulation for incipient sediment suspension considering the effect of cylinder density (i.e., solid volume fraction) is employed to simulate the bottom sediment flux in the flow with cylinders. The proposed model is calibrated and validated using laboratory measurements under unidirectional and combined wave-current flows in previous studies. It is proved that the effects of cylinders on sediment suspension can be accounted for through a modified critical Shields number, and the proposed model is capable of simulating sediment suspension under both unidirectional and combined wave–current flows reasonably well with the average the coefficients of determination and model skills greater than 0.8 and 0.64.
In vitro responses of human dermal fibroblasts to mechanical strain: A systematic review and meta-analysis
Authors: van Haasterecht L. , Dsouza C. , Ma Y. , Korkmaz H. I. , de Jong Y. , Ket J. C. F. , van Zuijlen P. P. M. , Groot M. L. , Komarova S. V.
Published: February 2023

In vitro research in the field of mechanotransducive regulation of dermal fibroblasts is characterized by highly variable methodology and contradictory results. The primary objective of this systematic review was to establish how in vitro mechanical stretch affects human dermal fibroblast function, by means of a quantitative synthesis of all available evidence. The secondary objectives were to examine the effects of covariates related to donor age, fibroblast origin, experimental treatments, and mechanical stimulation parameters on dermal fibroblast responsiveness to mechanical strain. Summary outcomes for fibroblast proliferation and collagen production were combined using a fixed-effects meta-analytical model. Subgroup analysis and meta-regression were used to investigate the effects of different conditions on the summary outcomes. Mechanical strain was found to not affect fibroblast proliferation in neonatal fibroblasts, while adult fibroblasts proliferation was significantly increased. Collagen production was significantly increased in response to mechanical stimulation, with Vitamin C stimulation as the most important covariate. Stretching frequency emerged as positively associated with fibroblast proliferation and negatively associated with collagen production. We conclude from this study that distinct differences exist in the effects of mechanical stretching between dermal fibroblasts from neonatal and adult donors, which will help to further elucidate the pathophysiological mechanism behind tension-induced scarring.
Archaea and their interactions with bacteria in a karst ecosystem
Authors: Cheng Xiaoyu , Xiang Xing , Yun Yuan , Wang Weiqi , Wang Hongmei , Bodelier Paul L. E.
Published: February 2023

Karst ecosystems are widely distributed around the world, accounting for 15–20% of the global land area. However, knowledge on microbial ecology of these systems does not match with their global importance. To close this knowledge gap, we sampled three niches including weathered rock, sediment, and drip water inside the Heshang Cave and three types of soils overlying the cave (forest soil, farmland soil, and pristine karst soil). All these samples were subjected to high-throughput sequencing of V4-V5 region of 16S rRNA gene and analyzed with multivariate statistical analysis. Overall, archaeal communities were dominated by Thaumarchaeota, whereas Actinobacteria dominated bacterial communities. Thermoplasmata, Nitrosopumilaceae, Aenigmarchaeales, Crossiella, Acidothermus, and Solirubrobacter were the important predictor groups inside the Heshang Cave, which were correlated to NH4+ availability. In contrast, Candidatus Nitrososphaera, Candidatus Nitrocosmicus, Thaumarchaeota Group 1.1c, and Pseudonocardiaceae were the predictors outside the cave, whose distribution was correlated with pH, Ca2+, and NO2−. Tighter network structures were found in archaeal communities than those of bacteria, whereas the topological properties of bacterial networks were more similar to those of total prokaryotic networks. Both chemolithoautotrophic archaea (Candidatus Methanoperedens and Nitrosopumilaceae) and bacteria (subgroup 7 of Acidobacteria and Rokubacteriales) were the dominant keystone taxa within the co-occurrence networks, potentially playing fundamental roles in obtaining energy under oligotrophic conditions and thus maintaining the stability of the cave ecosystem. To be noted, all the keystone taxa of karst ecosystems were related to nitrogen cycling, which needs further investigation, particularly the role of archaea. The predicted ecological functions in karst soils mainly related to carbohydrate metabolism, biotin metabolism, and synthesis of fatty acid. Our results offer new insights into archaeal ecology, their potential functions, and archaeal interactions with bacteria, which enhance our understanding about the microbial dark matter in the subsurface karst ecosystems.
The antibacterial activity and mechanism of imidazole chloride ionic liquids on Staphylococcus aureus
Authors: Hu Yanhui , Xing Yuyuan , Ye Peng , Yu Haikuan , Meng Xianglei , Song Yuting , Wang Gongying , Diao Yanyan
Published: February 2023

Ionic liquids (ILs) have garnered increasing attention in the biomedical field due to their unique properties. Although significant research has been conducted in recent years, there is still a lack of understanding of the potential applications of ILs in the biomedical field and the underlying principles. To identify the antibacterial activity and mechanism of ILs on bacteria, we evaluated the antimicrobial potency of imidazole chloride ILs (CnMIMCl) on Staphylococcus aureus (S. aureus). The toxicity of ILs was positively correlated to the length of the imidazolidinyl side chain. We selected C12MIMCl to study the mechanism of S. aureus. Through the simultaneous change in the internal and external parts of S. aureus, C12MIMCl caused the death of the bacteria. The production of large amounts of reactive oxygen species (ROS) within the internal parts stimulated oxidative stress, inhibited bacterial metabolism, and led to bacterial death. The external cell membrane could be destroyed, causing the cytoplasm to flow out and the whole cell to be fragmented. The antibacterial effect of C12MIMCl on skin abscesses was further verified in vivo in mice.