bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving acid resistance of Escherichia coli base on the CfaS-mediated membrane engineering strategy derived from extreme acidophile
Authors: Hu Wenbo , Tong Yanjun , Liu Junjie , Chen Panyan , Yang Hailin , Feng Shoushuai
Published: March 2023

Industrial microorganisms used for the production of organic acids often face challenges such as inhibited cell growth and reduced production efficiency due to the accumulation of acidic metabolites. One promising way for improving the acid resistance of microbial cells is to reconstruct their membranes. Herein, the overexpression of cfa2 from extreme acidophile endowed E. coli with high-performance on resistance to the acid stress. The engineered strain M1-93-Accfa2, constructed by CRISPR/Cas9-mediated chromosome integration, also exhibited a significantly higher resistance to severe acid stress. The analysis of fatty acid profiles indicated that the proportion of Cy-19:0 in the cell membrane of M1-93-Accfa2 increased by 5.26 times compared with the control, while the proportion of C18:1w9c decreased by 5.81 times. Correspondingly, the permeability and fluidity of the membrane decreased significantly. HPLC analysis demonstrated that the contents of intracellular glutamic acid, arginine, methionine and aspartic acid of M1-93-Accfa2 were 2.59, 2.04, 22.07 and 2.65 times that of the control after environmental acidification, respectively. Meanwhile, transmission electron microscopy observation indicated that M1-93-Accfa2 could maintain a plumper cell morphology after acid stimulation. M1-93-Accfa2 also exhibited higher-performance on the resistance to organic acids, especially succinic acid stress. These results together demonstrated the great potential of M1-93-Accfa2 constructed here in the production of organic acids.
Surface decorated quantum dots: Synthesis, properties and role in herbal therapy
Authors: Baig Mirza Shahed , Suryawanshi Ravikiran Maheshrao , Zehravi Mehrukh , Mahajan Hitendra S. , Rana Ritesh , Banu Ahemadi , Subramanian Muthukumar , Kaundal Amit Kumar , Puri Sachin , Siddiqui Falak A. , Sharma Rohit , Khan Sharuk L. , Chen Kow-Tong , Emran Talha Bin
Published: March 2023

Quantum dots are the serendipitous outcome of materials research. It is the tiny carbonaceous nanoparticles with diameters ranging from 1 to 10 nm. This review is a brief discussion of the synthesis, properties, and biomedical applicability of quantum dots, especially in herbal therapy. As quantum dots are highly polar, they can be surface decorated with several kinds of polar functionalities, such as polymeric molecules, small functional molecules, and so on. The review also consists of the basic physical and optical properties of quantum dots and their excitation―dependent properties in the application section. We focus on therapeutics, where quantum dots are used as drugs or imaging probes. Nanoprobes for several diagnostics are quite new in the biomedical research domain. Quantum dot―based nanoprobes are in high demand due to their excellent fluorescence, non-bleaching nature, biocompatibility, anchoring feasibility for several analytes, and fast point―of―care sensibility. Lastly, we also included a discussion on quantum dot―based drug delivery as phytomedicine.
Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing
Authors: Wakabayashi Taku , Naito Hisamichi
Published: March 2023

Vascular endothelial cells (ECs) that constitute the inner surface of blood vessels are essential for new vessel formation and organ homeostasis. ECs display remarkable phenotypic heterogeneity across different organs and the vascular tree during angiogenesis and homeostasis. Recent advances in single cell RNA sequencing (scRNA-seq) technologies have allowed a new understanding of EC heterogeneity in both mice and humans. In particular, scRNA-seq has identified new molecular signatures for arterial, venous and capillary ECs in different organs, as well as previously unrecognized specialized EC subtypes, such as the aerocytes localized in the alveolar capillaries of the lung. scRNA-seq has also revealed the gene expression profiles of specialized tissue-resident EC subtypes that are capable of clonal expansion and contribute to adult angiogenesis, a process of new vessel formation from the pre-existing vasculature. These specialized tissue-resident ECs have been identified in various different mouse tissues, including aortic endothelium, liver, heart, lung, skin, skeletal muscle, retina, choroid, and brain. Transcription factors and signaling pathways have also been identified in the specialized tissue-resident ECs that control angiogenesis. Furthermore, scRNA-seq has also documented responses of ECs in diseases such as cancer, age-related macular degeneration, Alzheimer’s disease, atherosclerosis, and myocardial infarction. These new findings revealed by scRNA-seq have the potential to provide new therapeutic targets for different diseases associated with blood vessels. In this article, we summarize recent advances in the understanding of the vascular endothelial cell heterogeneity and endothelial stem cells associated with angiogenesis and homeostasis in mice and humans, and we discuss future prospects for the application of scRNA-seq technology.
Organoids in high-throughput and high-content screenings
Authors: Lampart Franziska L. , Iber Dagmar , Doumpas Nikolaos
Published: March 2023

Organoids are self-organized three-dimensional (3D) multicellular tissue cultures which derive from cancerous and healthy stem cells, sharing a highly similarity to the corresponding in vivo organs. Since their introduction in 2009, they have emerged as a valuable model for studying early embryogenesis, organ and tissue development, as well as tools in drug screening, disease modeling and personalized therapy. Organoids can now be established for various tissues, including brain, retina, thyroid, gastrointestinal, lung, liver, pancreas, and kidney. These micro-tissues resemble the native organ in terms of gene expression, protein expression, tissue architecture and cell-cell interactions. Despite the success of organoid-based research and the advances in patient-derived organoid culture, important challenges remain. In this review, we briefly showcase the evolution from the primary 3D systems to complex, multilayered 3D structures such as assembloids, gastruloids and ETiX embryoids. We discuss current developments in organoid research and highlight developments in organoid culturing systems and analysis tools which make organoids accessible for high-throughput and high-content screening. Finally, we summarize the potential of machine learning and computational modeling in conjunction with organoid systems.
USP8 inhibition regulates autophagy flux and controls Salmonella infection
Authors: Santelices John , Ou Mark , Maegawa Gustavo H. B. , Hercik Kamil , Edelmann Mariola J.
Published: March 2023

Introduction

Ubiquitination is an important protein modification that regulates various essential cellular processes, including the functions of innate immune cells. Deubiquitinases are enzymes responsible for removing ubiquitin modification from substrates, and the regulation of deubiquitinases in macrophages during infection with Salmonella Typhimurium and Yersinia enterocolitica remains unknown.

Methods

To identify deubiquitinases regulated in human macrophages during bacterial infection, an activity-based proteomics screen was conducted. The effects of pharmacological inhibition of the identified deubiquitinase, USP8, were examined, including its impact on bacterial survival within macrophages and its role in autophagy regulation during Salmonella infection.

Results

Several deubiquiitnases were differentially regulated in infected macrophages. One of the deubiquitinases identified was USP8, which was downregulated upon Salmonella infection. Inhibition of USP8 was associated with a decrease in bacterial survival within macrophages, and it was found to play a distinct role in regulating autophagy during Salmonella infection. The inhibition of USP8 led to the downregulation of the p62 autophagy adaptor.

Discussion

The findings of this study suggest a novel role of USP8 in regulating autophagy flux, which restricts intracellular bacteria, particularly during Salmonella infection.
Case report: Aggressive progression of acute heart failure due to juvenile tuberculosis-associated Takayasu arteritis with aortic stenosis and thrombosis
Authors: Xuan Wenjie , Wang Zhaoling , Lin Jinjing , Zou Lixia , Xu Xisheng , Yang Xinghui , Xu Yiping , Zhang Yan , Zheng Qi , Xu Xuefeng , Lu Meiping
Published: March 2023

Background

Takayasu arteritis (TA) is a chronic granulomatous vasculitis with unknown pathophysiology. TA with severe aortic obstruction has a poor prognosis. However, the efficacy of biologics and appropriate timing of surgical intervention remain controversial. We report a case of tuberculosis (TB)-associated TA with aggressive acute heart failure (AHF), pulmonary hypertension (PH), thrombosis, and seizure, who failed to survive after surgery.

Case presentation

A 10-year-old boy who developed a cough with chest tightness, shortness of breath, hemoptysis with reduced left ventricular ejection fraction, PH, and increased C-reactive protein and erythrocyte sedimentation rate was hospitalized at the pediatric intensive care unit of our hospital. He had strongly positive purified protein derivative skin test and interferon-gamma release assay result. Computed tomography angiography (CTA) showed occlusion of proximal left subclavian artery and stenosis of descending aorta and upper abdominal aorta. His condition did not improve after administration of milrinone, diuretics, antihypertensive agents, and intravenous methylprednisolone pulse followed by oral prednisone. Intravenous tocilizumab was administered for five doses, followed by two doses of infliximab, but his HF worsened, and CTA on day 77 showed complete occlusion of the descending aorta with large thrombus. He had a seizure on day 99 with deterioration of renal function. Balloon angioplasty and catheter-directed thrombolysis were performed on day 127. Unfortunately, the child's heart function continued to deteriorate and died on day 133.

Conclusion

TB infection may be related to juvenile TA. The biologics, thrombolysis, and surgical intervention failed to achieve the anticipated effect in our case with aggressive AHF due to severe aortic stenosis and thrombosis. More studies are needed to determine the role of biologics and surgery in such dire cases.
The risk of long-term cardiometabolic disease in women with premature or early menopause: A systematic review and meta-analysis
Authors: Liu Jiajun , Jin Xueshan , Liu Wenbin , Chen Wanying , Wang Lan , Feng Ziyi , Huang Jieming
Published: March 2023

Background

Transition into menopause is associated with an increased risk of cardiovascular disease (CVD). However, it is unclear whether the association exists between premature menopause (defined as age at menopause 40 years) or early menopause (defined as age at menopause 40–45 years) and CVD or cardiovascular risk factors. The aim of this review was to comprehensively evaluate and meta-analyze the most reliable evidence about the relationship between menopausal age and the risk of long-term cardiometabolic disease.

Methods

A comprehensive literature search of the PubMed, Web of Science, and Embase databases from inception to October 1, 2022, for titles and abstracts with a restriction to English language papers led to the discovery of the studies. Data are expressed as the Hazard Ratio (HR) with 95% confidence intervals (CI). The degree of heterogeneity was measured using the I-square (I2) index.

Results

921,517 participants from 20 cohort studies published between 1998 and 2022 were considered. Compared to women with menopause at age >45 years, women with premature menopause (PM) or early menopause (EM) had a higher risks of type 2 diabetes (RR: 1.32, 95% CI: 1.08–1.62; RR: 1.11, 95% CI: 0.91–1.36, respectively), hyperlipidemia (RR: 1.21, 95% CI: 1.05–1.39; RR: 1.17, 95% CI: 1.02–1.33, respectively), coronary heart disease (RR: 1.52, 95% CI: 1.22–1.91; RR: 1.19, 95% CI: 1.07–1.32, respectively), stroke (RR: 1.27, 95% CI: 1.02–1.58; RR: 1.13, 95% CI: 0.97–1.32, respectively) and total cardiovascular event (RR: 1.36, 95% CI: 1.16–1.60; RR: 1.14, 95% CI: 0.97–1.35, respectively). No difference was found for hypertension in PM or EM women (RR: 0.98, 95% CI: 0.89–1.07; RR: 0.97, 95% CI: 0.91–1.04, respectively). Additionally, we also found that PM women, but not EM women, were linked with an increased risk of ischemic and hemorrhagic stroke. However, this is not in line with the conclusion that both PM and EM had a higher risk of total stroke.

Conclusion

Women with PM or EM have a higher risk of developing long-term CVD, compared to women with menopause at age >45 years. Therefore, we recommend early lifestyle interventions (e.g., maintaining a healthy lifestyle) and medical treatments (e.g., timely initiation of menopausal hormone therapy) to decrease the risk of cardiometabolic disease in early or premature menopausal women.

Systematic Review Registration

PROSPERO, identifier CRD42022378750
Establishment of a nomogram model for acute chest pain triage in the chest pain center
Authors: Yan Na , Wei Ling , Li Zhiwei , Song Yu
Published: March 2023

Background

Acute myocardial infarction (AMI) is the leading life-threatening disease in the emergency department (ED), so rapid chest pain triage is important. This study aimed to establish a clinical prediction model for the risk stratification of acute chest pain patients based on the Point-of-care (POC) cardiac troponin (cTn) level and other clinical variables.

Methods

We conducted a post-hoc analysis of the database from 6,019 consecutive patients (excluding prehospital-diagnosed non-cardiac chest pain patients) attending a local chest pain center (CPC) in China between October 2016 and January 2019. The plasma concentration of cardiac troponin I (cTnI) was measured using a POC cTnI (Cardio Triage, Alere) assay. All the eligible patients were randomly divided into training and validation cohorts by a 7:3 ratio. We performed multivariable logistic regression to select variables and build a nomogram based on the significant predictive factors. We evaluated the model's generalization ability of diagnostic accuracy in the validation cohort.

Results

We analyzed data from 5,397 patients that were included in this research. The median turnaround time (TAT) of POC cTnI was 16 min. The model was constructed with 6 variables: ECG ischemia, POC cTnI level, hypotension, chest pain symptom, Killip class, and sex. The area under the ROC curve (AUC) in the training and validation cohorts was 0.924 and 0.894, respectively. The diagnostic performance was superior to the GRACE score (AUC: 0.737).

Conclusion

A practical predictive model was created and could be used for rapid and effective triage of acute chest pain patients in the CPC.
Factors contributing to morning rain in the upper Río Chagres Basin, Panamá
Authors: Ishizaki Noriko N. , Nakaegawa Tosiyuki , Pinzón Reinhardt , Sasaki Hidetaka
Published: March 2023

The Upper Chagres River Basin plays an important role in the stable operation of the Panama Canal. Previous studies have shown that there is a salient regional difference in the diurnal variation of precipitation in the basin. Precipitation during the rainy season peaks in the early afternoon throughout the basin, but precipitation is also observed in the morning at sites in the northern part of the basin. However, the cause of this is not clear due to limited ground observation. To address this issue, we conducted dynamical downscaling experiments with a horizontal grid spacing of 5 and 2 km and nested in a global atmospheric model with horizontal grid spacing of approximately 20 km. The results showed that the 2 km convection-permitting model successfully reproduced regional differences in observed diurnal variations. The downscaled results indicated that intensified low-level northeasterly winds over the southern Caribbean Sea triggered favorable conditions for morning rain with an orographic effect under the seaside coastal regime in the western Caribbean Sea. This is in contrast to precipitation peaks in the early afternoon under a landside coastal regime.
An in-situ modification method for coal roadways with heightened burst risk
Authors: Ouyang Zhenhua , Li Gen , Wang Qiong , Yi Haiyang , Li Zhengsheng , Shi Qingwen
Published: March 2023

It is hard to control roadways effectively with a heightened burst risk using conventional support techniques, which may cause burst fatalities in the coal mine. Thus, an in-situ modification method, which involves artificially constructing a cracked zone and a reinforced zone, was proposed to improve the stability of the roadways with heightened burst risk. This paper investigated the efficiency to non of the in-situ modification method in improving burstroadway safety by performing a physical experiment. The results of the experiment indicated that the dynamic stress was obviously reduced in the modified roadway. Accordingly, the influence factors of the in-situ modification method were explored using numerical simulation. It was found that the thickness and the degree of damage to the cracked zone were key governing factors in reducing energy and improving roadway stability. The energy dissipation value increased as the thickness and the degree of damage to the cracked zone increased but showed a slower growth trend when the thickness and the degree of damage to the cracked zone increased to a certain value. In addition, the high sensitivity to dynamic load was found in parts of the roadway side exhibiting a larger stress reduction rate even with thinner cracked zone thickness and a lower degree of damage. This research provides an effective and economical method for coal roadways with heightened burst risk.
Diabetic endothelial microangiopathy and pulmonary dysfunction
Authors: Zhang Lanlan , Jiang Faming , Xie Yingying , Mo Yan , Zhang Xin , Liu Chuntao
Published: March 2023

Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with a high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by the macrovascular and microvascular bed degradation brought on by metabolic, hemodynamic, and inflammatory variables. However, research in recent years has expanded the target organ in T2DM to include the lung. Inflammatory lung diseases also impose a severe financial burden on global healthcare. T2DM has long been recognized as a significant comorbidity that influences the course of various respiratory disorders and their disease progress. The pathogenesis of the glycemic metabolic problem and endothelial microangiopathy of the respiratory disorders have garnered more attention lately, indicating that the two ailments have a shared history. This review aims to outline the connection between T2DM related endothelial cell dysfunction and concomitant respiratory diseases, including Coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
Impact of COVID-19 during pregnancy on placental pathology, maternal and neonatal outcome – A cross-sectional study on anemic term pregnant women from a tertiary care hospital in southern India
Authors: Surekha M. V. , Suneetha N. , Balakrishna N. , Putcha Uday Kumar , Satyanarayana K. , Geddam J. J. Babu , Sreenu Pagidoju , Tulja B. , Mamidi Raja Sriswan , Rutter Guy A. , Meur Gargi
Published: March 2023

Background

SARS-CoV-2 infection during pregnancy may cause adverse maternal, neonatal and placental outcomes. While tissue hypoxia is often reported in COVID-19 patients, pregnant women with anemia are suspected to be more prone to placental hypoxia-related injuries.

Methods

This hospital-based cross-sectional study was conducted between August-November 2021, during COVID-19 second wave in India. Term pregnant women (N=212) admitted to hospital for delivery were enrolled consecutively. Since hospital admission mandated negative RT-PCR test for SARS-CoV-2 virus, none had active infection. Data on socio-demography, COVID-19 history, maternal, obstetric, and neonatal outcomes were recorded. Pre-delivery maternal and post-delivery cord blood samples were tested for hematological parameters and SARS-CoV-2 IgG. Placentae were studied for histology.

Results

Of 212 women, 122 (58%) were seropositive for SARS-CoV-2 IgG, but none reported COVID-19 history; 134 (63.2%) were anemic. In seropositive women, hemoglobin (p=0.04), total WBC (p=0.009), lymphocytes (p=0.005) and neutrophils (p=0.02) were significantly higher, while ferritin was high, but not significant and neutrophils to lymphocytes (p=0.12) and platelets to lymphocytes ratios (p=0.03) were lower. Neonatal outcomes were similar. All RBC parameters and serum ferritin were significantly lower in anemic mothers but not in cord blood, except RDW that was significantly higher in both, maternal (p=0.007) and cord (p=0.008) blood from seropositive anemic group compared to other groups. Placental histology showed significant increase in villous hypervascularity (p=0.000), dilated villous capillaries (p=0.000), and syncytiotrophoblasts (p=0.02) in seropositive group, typically suggesting placental hypoxia. Maternal anemia was not associated with any histological parameters. Univariate and multivariate logistic regression analyses of placental histopathological adverse outcomes showed strong association with SARS-CoV-2 seropositivity but not with maternal anemia. When adjusted for several covariates, including anemia, SARS-CoV-2 seropositivity emerged as independent risk factor for severe chorangiosis (AOR 8.74, 95% CI 3.51-21.76, p<0.000), dilated blood vessels (AOR 12.74, 95% CI 5.46-29.75, p<0.000), syncytiotrophoblasts (AOR 2.86, 95% CI 1.36-5.99, p=0.005) and villus agglutination (AOR 9.27, 95% CI 3.68-23.32, p<0.000).

Conclusion

Asymptomatic COVID-19 during pregnancy seemed to be associated with various abnormal placental histopathologic changes related to placental hypoxia independent of maternal anemia status. Our data supports an independent role of SARS-CoV-2 in causing placental hypoxia in pregnant women.
Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women
Authors: Williams Camille Y. , Wylie Amanda , Ghobrial Verina , Coe Christopher L. , Short Sarah J.
Published: March 2023

Background

The prevalence of obesity among women of child-bearing age has contributed to an increased risk of pregnancy complications with a disproportional impact on women of lower socioeconomic status and among certain racial groups. In particular, socio-demographic and historical factors have resulted in higher rates of premature births and small-for-gestational age infants among Black women, which may be associated with placental function during pregnancy. The current study investigated the influence of maternal pre-pregnancy adiposity and race on the associations between inflammatory proteins, placental growth hormone (PGH), and infant birthweight. This information was collected for a subsample of 109 participants (Black, n = 39 vs. White, n = 70) from the Brain and Early Experiences (BEE) study.

Methods

Serum samples were acquired late in the second trimester to assess PGH levels, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin-1 receptor antagonist (IL-1Ra). Participant questionnaire responses provided information on pre-pregnancy BMI, health, race, educational attainment, and infant birthweight. Bivariate correlations and multiple linear regression models were utilized to evaluate associations by race between preconception adiposity, inflammatory markers and PGH.

Results

After controlling for covariates including maternal age and education, gestational age, and fetal sex, regression models indicated that pre-pregnancy BMI was negatively associated with PGH (β=-0.42, p<0.05) and IL-8 was positively associated with PGH (β=0.35, p<0.05) among the Black mothers only; neither were significantly associated with PGH in the White mothers. When extending models to birth outcomes, BMI was positively associated with birthweight corrected for gestational age (BWz) (β=0.24, p<0.05) and educational attainment was negatively associated with BWz (β=0.28, p<0.05) for infants of White women. In contrast, neither variable was predictive of BWz for infants of Black mothers.

Conclusion

Future work is needed to investigate racial differences in the association between adiposity and placental functioning, which are likely to contribute to differential effects on pregnancy outcomes and fetal growth.
MRI-based porosity index (PI) and suppression ratio (SR) in the tibial cortex show significant differences between normal, osteopenic, and osteoporotic female subjects
Authors: Jerban Saeed , Ma Yajun , Moazamian Dina , Athertya Jiyo , Dwek Sophia , Jang Hyungseok , Woods Gina , Chung Christine B. , Chang Eric Y. , Du Jiang
Published: March 2023

Introduction

Ultrashort echo time (UTE) MRI enables quantitative assessment of cortical bone. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques developed to reduce the time demand and cost in future clinical studies. The goal of this study was to investigate the performance of PI and SR in detecting bone quality differences between subjects with osteoporosis (OPo), osteopenia (OPe), and normal bone (Normal).

Methods

Tibial midshaft of fourteen OPe (72 ± 6 years old), thirty-one OPo (72 ± 6 years old), and thirty-seven Normal (36 ± 19 years old) subjects were scanned using dual-echo UTE and IR-UTE sequences on a clinical 3T scanner. Measured PI, SR, and bone thickness were compared between OPo, OPe, and normal bone (Normal) subjects using the Kruskal–Wallis test by ranks. Spearman’s rank correlation coefficients were calculated between dual-energy x-ray absorptiometry (DEXA) T-score and UTE-MRI results.

Results

PI was significantly higher in the OPo group compared with the Normal (24.1%) and OPe (16.3%) groups. SR was significantly higher in the OPo group compared with the Normal (41.5%) and OPe (21.8%) groups. SR differences between the OPe and Normal groups were also statistically significant (16.2%). Cortical bone was significantly thinner in the OPo group compared with the Normal (22.0%) and OPe (13.0%) groups. DEXA T-scores in subjects were significantly correlated with PI (R=-0.32), SR (R=-0.50), and bone thickness (R=0.51).

Discussion

PI and SR, as rapid UTE-MRI-based techniques, may be useful tools to detect and monitor bone quality changes, in addition to bone morphology, in individuals affected by osteoporosis.
Does capital market liberalization promote ESG disclosure? Empirical evidence from the mainland-HK stock connect
Authors: Nie Mingjian , Chen Changyu , Song Chang , Qin Chao
Published: March 2023

With the growing popularity of environmental, social, and governance (ESG), ESG performance is becoming increasingly important in investors’ decisions about firms. Capital market liberalization brings in more sophisticated and mature foreign investors who are more interested in corporate ESG performance. We investigate whether capital market liberalization improves corporate ESG disclosure using Shanghai-Hong Kong Stock Connect and Shenzhen-Hong Kong Stock Connect as exogenous shocks. By compiling a comprehensive dataset of Chinese A-share listed firms from 2006 to 2019 and manually calculating the ESG disclosure score, we find that the mainland-HK Stock Connect scheme enhances corporate ESG disclosure. This effect is heterogeneous for firms with different external environments, corporate characteristics, and environmental performance. The results suggest that the competition effect dominates the role of capital market liberalization in improving ESG disclosure of mainland listed firms and firms disclose their ESG practices to cater to the need of investors. This paper enriches the empirical research on the impact of capital market liberalization on firm behavior and performance and provides a theoretical basis for strengthening regulations in ESG information disclosure.
A self-training subspace clustering algorithm based on adaptive confidence for gene expression data
Authors: Li Dan , Liang Hongnan , Qin Pan , Wang Jia
Published: March 2023

Gene clustering is one of the important techniques to identify co-expressed gene groups from gene expression data, which provides a powerful tool for investigating functional relationships of genes in biological process. Self-training is a kind of important semi-supervised learning method and has exhibited good performance on gene clustering problem. However, the self-training process inevitably suffers from mislabeling, the accumulation of which will lead to the degradation of semi-supervised learning performance of gene expression data. To solve the problem, this paper proposes a self-training subspace clustering algorithm based on adaptive confidence for gene expression data (SSCAC), which combines the low-rank representation of gene expression data and adaptive adjustment of label confidence to better guide the partition of unlabeled data. The superiority of the proposed SSCAC algorithm is mainly reflected in the following aspects. 1) In order to improve the discriminative property of gene expression data, the low-rank representation with distance penalty is used to mine the potential subspace structure of data. 2) Considering the problem of mislabeling in self-training, a semi-supervised clustering objective function with label confidence is proposed, and a self-training subspace clustering framework is constructed on this basis. 3) In order to mitigate the negative impact of mislabeled data, an adaptive adjustment strategy based on gravitational search algorithm is proposed for label confidence. Compared with a variety of state-of-the-art unsupervised and semi-supervised learning algorithms, the SSCAC algorithm has demonstrated its superiority through extensive experiments on two benchmark gene expression datasets.
Furious depletion—Conceptualizing artisan mining and extractivism through gender, race, and environment
Authors: Côte Muriel
Published: March 2023

A buoyant debate has grown in political ecology and agrarian studies around the concept of extractivism. It shines a light on forms of human and non-human depletion that fuel contemporary capitalism. Within this debate however, artisan mining has been hard to fit in. Artisan mining is a form of small scale mineral extraction that occupies around 45 million people around the world, and sustains the life of many more, especially in the Global South. Much research has looked at this expanding form of livelihood, particularly through the prism of its persistent informality, its labor organization, and its challenges to environmental and labor rights. However, it has not been well-theorized in relations to extractivism, sitting uncomfortably with dominant categories such as “the community”, “the company”, and “social movements” in political ecology analyses. The paper maps out entry points to studying the significance of artisan mining within dynamics of extractive capitalism by bringing in conversation political ecology scholarship on extractivism and research on artisan mining through a feminist lens. It develops the notions of “furious depletion”, attempting to capture the stark socioenvironmental injustice through which artisan mining forms an integral part of extractive capitalism, as both a victim and fuel thereof. The notion also emphasizes the significance of emotions - such as infuriation - in thinking through unjust human-environment relations for transformation. It focuses specifically on the ways relations of gender and race mediate human-environment relations, can help clarify an understanding of artisan mining in the depletion dynamics underlying extractivism. Given the acceleration of mining as part of digital and energy transitions, and the expansion of artisan mining, an engaged conceptualization of artisan mining may support struggles away from extractive capitalism for the decades to come.
Abnormal thrombosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients
Authors: Narang Jatin , Jatana Samreen , Ponti András K. , Musich Ryan , Gallop Joshua , Wei Angela H. , Seck Sokhna , Johnson Jessica , Kokoczka Lynne , Nowacki Amy S. , McBride Jeffrey D. , Mireles-Cabodevila Eduardo , Gordon Steven , Cooper Kevin , Fernandez Anthony P. , McDonald Christine
Published: March 2023

Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19.
CRISPR/Cas9-engineering of HMC-1.2 cells renders a human mast cell line with a single D816V-KIT mutation: An improved preclinical model for research on mastocytosis
Authors: Bandara Geethani , Falduto Guido H. , Luker Andrea , Bai Yun , Pfeiffer Annika , Lack Justin , Metcalfe Dean D. , Olivera Ana
Published: March 2023

The HMC-1.2 human mast cell (huMC) line is often employed in the study of attributes of neoplastic huMCs as found in patients with mastocytosis and their sensitivity to interventional drugs in vitro and in vivo. HMC-1.2 cells express constitutively active KIT, an essential growth factor receptor for huMC survival and function, due to the presence of two oncogenic mutations (D816V and V560G). However, systemic mastocytosis is commonly associated with a single D816V-KIT mutation. The functional consequences of the coexisting KIT mutations in HMC-1.2 cells are unknown. We used CRISPR/Cas9-engineering to reverse the V560G mutation in HMC-1.2 cells, resulting in a subline (HMC-1.3) with a single mono-allelic D816V-KIT variant. Transcriptome analyses predicted reduced activity in pathways involved in survival, cell-to-cell adhesion, and neoplasia in HMC-1.3 compared to HMC-1.2 cells, with differences in expression of molecular components and cell surface markers. Consistently, subcutaneous inoculation of HMC-1.3 into mice produced significantly smaller tumors than HMC-1.2 cells, and in colony assays, HMC-1.3 formed less numerous and smaller colonies than HMC-1.2 cells. However, in liquid culture conditions, the growth of HMC-1.2 and HMC-1.3 cells was comparable. Phosphorylation levels of ERK1/2, AKT and STAT5, representing pathways associated with constitutive oncogenic KIT signaling, were also similar between HMC-1.2 and HMC-1.3 cells. Despite these similarities in liquid culture, survival of HMC-1.3 cells was diminished in response to various pharmacological inhibitors, including tyrosine kinase inhibitors used clinically for treatment of advanced systemic mastocytosis, and JAK2 and BCL2 inhibitors, making HMC-1.3 more susceptible to these drugs than HMC-1.2 cells. Our study thus reveals that the additional V560G-KIT oncogenic variant in HMC-1.2 cells modifies transcriptional programs induced by D816V-KIT, confers a survival advantage, alters sensitivity to interventional drugs, and increases the tumorigenicity, suggesting that engineered huMCs with a single D816V-KIT variant may represent an improved preclinical model for mastocytosis.
Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19
Authors: Matthay Zachary A. , Fields Alexander T. , Wick Katherine D. , Jones Chayse , Lane H. Clifford , Herrera Kimberly , Nuñez-Garcia Brenda , Gennatas Efstathios , Hendrickson Carolyn M. , Kornblith Aaron E. , Matthay Michael A. , Kornblith Lucy Z. ,   the COVID-19 Associated Coagulopathy Inflammation Thrombosis (Co-ACIT) Study Group
Published: March 2023

Introduction

There remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19.

Methods

Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured.

Results

Differences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis.

Discussion

Elevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.
PCSK9 regulates the efficacy of immune checkpoint therapy in lung cancer
Authors: Gao Xiang , Yi Ling , Jiang Chang , Li Shuping , Wang Xiaojue , Yang Bin , Li Weiying , Che Nanying , Wang Jinghui , Zhang Hongtao , Zhang Shucai
Published: March 2023

Proprotein convertase subtilisin/kexin type 9 (PCSK9) secreted by tumors was reported as a deleterious factor that led to the reduction of lymphocyte infiltration and the poorer efficacy of ICIs in vivo. This study aimed to explore whether PCSK9 expression in tumor tissue could predict the response of advanced non-small cell lung cancer (NSCLC) to anti-PD-1 immunotherapy and the synergistic antitumor effect of the combination of the PCSK9 inhibitor with the anti-CD137 agonist. One hundred fifteen advanced NSCLC patients who received anti-PD-1 immunotherapy were retrospectively studied with PCSK9 expression in baseline NSCLC tissues detected by immunohistochemistry (IHC). The mPFS of the PCSK9lo group was significantly longer than that of the PCSK9hi group [8.1 vs. 3.6 months, hazard ratio (HR): 3.450; 95% confidence interval (CI), 2.166-5.496]. A higher objective response rate (ORR) and a higher disease control rate (DCR) were observed in the PCSK9lo group than in the PCSK9hi group (54.4% vs. 34.5%, 94.7% vs. 65.5%). Reduction and marginal distribution of CD8+ T cells were observed in PCSK9hi NSCLC tissues. Tumor growth was retarded by the PCSK9 inhibitor and the anti-CD137 agonist alone in the Lewis lung carcinoma (LLC) mice model and further retarded by the PCSK9 inhibitor in combination with the CD137 agonist with long-term survival of the host mice with noticeable increases of CD8+ and GzmB+ CD8+ T cells and reduction of Tregs. Together, these results suggested that high PCSK9 expression in baseline tumor tissue was a deleterious factor for the efficacy of anti-PD-1 immunotherapy in advanced NSCLC patients. The PCSK9 inhibitor in combination with the anti-CD137 agonist could not only enhance the recruitment of CD8+ and GzmB+ CD8+ T cells but also deplete Tregs, which may be a novel therapeutic strategy for future research and clinical practice.
Identification of common molecular signatures of SARS-CoV-2 infection and its influence on acute kidney injury and chronic kidney disease
Authors: Zhang Weiwei , Liu Leping , Xiao Xiangcheng , Zhou Hongshan , Peng Zhangzhe , Wang Wei , Huang Ling , Xie Yanyun , Xu Hui , Tao Lijian , Nie Wannian , Yuan Xiangning , Liu Fang , Yuan Qiongjing
Published: March 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main cause of COVID-19, causing hundreds of millions of confirmed cases and more than 18.2 million deaths worldwide. Acute kidney injury (AKI) is a common complication of COVID-19 that leads to an increase in mortality, especially in intensive care unit (ICU) settings, and chronic kidney disease (CKD) is a high risk factor for COVID-19 and its related mortality. However, the underlying molecular mechanisms among AKI, CKD, and COVID-19 are unclear. Therefore, transcriptome analysis was performed to examine common pathways and molecular biomarkers for AKI, CKD, and COVID-19 in an attempt to understand the association of SARS-CoV-2 infection with AKI and CKD. Three RNA-seq datasets (GSE147507, GSE1563, and GSE66494) from the GEO database were used to detect differentially expressed genes (DEGs) for COVID-19 with AKI and CKD to search for shared pathways and candidate targets. A total of 17 common DEGs were confirmed, and their biological functions and signaling pathways were characterized by enrichment analysis. MAPK signaling, the structural pathway of interleukin 1 (IL-1), and the Toll-like receptor pathway appear to be involved in the occurrence of these diseases. Hub genes identified from the protein–protein interaction (PPI) network, including DUSP6, BHLHE40, RASGRP1, and TAB2, are potential therapeutic targets in COVID-19 with AKI and CKD. Common genes and pathways may play pathogenic roles in these three diseases mainly through the activation of immune inflammation. Networks of transcription factor (TF)–gene, miRNA–gene, and gene–disease interactions from the datasets were also constructed, and key gene regulators influencing the progression of these three diseases were further identified among the DEGs. Moreover, new drug targets were predicted based on these common DEGs, and molecular docking and molecular dynamics (MD) simulations were performed. Finally, a diagnostic model of COVID-19 was established based on these common DEGs. Taken together, the molecular and signaling pathways identified in this study may be related to the mechanisms by which SARS-CoV-2 infection affects renal function. These findings are significant for the effective treatment of COVID-19 in patients with kidney diseases.
A first-year maize/cassava relay intercropping system improves soil nutrients and changes the soil microbial community in the symbiotic period
Authors: He Cuicui , Zhou Bin , Wang Hua , Wei Yunxia , Huang Jie
Published: March 2023

The maize/cassava relay intercropping system can be a specific and efficient cropping pattern in a tropical/subtropical field. Relay intercropping systems contribute to the optimization of land use, fostering sustainable and efficient agriculture. This study entails a first-year comparative intercropping experiment using maize (Zea mays L.) and cassava (Manihot esculenta Crantz). We determined the soil nutrient contents and physicochemical properties as well as the microbial communities by high-throughput sequencing. We found that the relay intercropping system changed the bacterial community structure, especially the rhizosphere microorganisms. The bacterial community was characterized by a higher abundance of the phyla Chloroflexi, Proteobacteria, and Actinobacteria and of the genus AD3, which are related to nutrient cycling and decreased bioavailability of Cd. At the same time, the relay intercropping system reduces the relative abundance of pathogenic bacteria and biomarkers of organic pollution. The relay intercropping systems significantly boosted soil pH and available K levels in addition to the monocropping yield. The results of this study suggest that maize/cassava relay intercropping, starting from the first year, not only provides a stable supply of food and income due to the diversified cropping systems but is also beneficial for the improvement of soil quality and the soil microbial community.
Modulation of the nanoscale motion rate of Candida albicans by X-rays
Authors: Starodubtseva Maria N. , Chelnokova Irina A. , Shkliarava Nastassia M. , Villalba María Inés , Tapalski Dmitry V. , Kasas Sandor , Willaert Ronnie G.
Published: March 2023

Introduction

Patients undergoing cancer treatment by radiation therapy commonly develop Candida albicans infections (candidiasis). Such infections are generally treated by antifungals that unfortunately also induce numerous secondary effects in the patient. Additional to the effect on the immune system, ionizing radiation influences the vital activity of C. albicans cells themselves; however, the reaction of C. albicans to ionizing radiation acting simultaneously with antifungals is much less well documented. In this study, we explored the effects of ionizing radiation and an antifungal drug and their combined effect on C. albicans.

Methods

The study essentially relied on a novel technique, referred to as optical nanomotion detection (ONMD) that monitors the viability and metabolic activity of the yeast cells in a label and attachment-free manner.

Results and discussion

Our findings demonstrate that after exposure to X-ray radiation alone or in combination with fluconazole, low-frequency nanoscale oscillations of whole cells are suppressed and the nanomotion rate depends on the phase of the cell cycle, absorbed dose, fluconazole concentration, and post-irradiation period. In a further development, the ONMD method can help in rapidly determining the sensitivity of C. albicans to antifungals and the individual concentration of antifungals in cancer patients undergoing radiation therapy.