bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of UDP-glucose ceramide glucosyltransferase in venous malformation
Authors: Chen Sheng , Wang Yuan , Kong Liangliang , Ji Yi , Cui Jie , Shen Weimin
Published: May 2023

Venous malformation (VM) results from the abnormal growth of the vasculature; however, the detailed molecular mechanism remains unclear. As a glycosyltransferase, UDP-glucose ceramide glucosyltransferase (UGCG) is localized to the Golgi body and is a key enzyme in the first step of glycosphingolipid synthesis. Here, we aimed to explore the relationship between UGCG and the development of VM. First, investigations using RT-qPCR and Western blotting on the diseased vasculature of VM patients and normal vascular tissues revealed that UGCG expression was markedly elevated in the diseased vessels. Subsequently, immunofluorescence assay showed that UGCG was co-localized with CD31, an endothelial cell marker, in tissues from patients with VM and healthy subjects. Then, we established TIE2-L914F-mutant human umbilical vein endothelial cells (HUVECs) by lentivirus transfection. Next, Western blotting revealed that UGCG expression was considerably higher in HUVECsTIE2-L914F. In addition, we established a UGCG-overexpressing HUVECs line by plasmid transfection. With the CCK8 cell proliferation experiment, wound healing assay, and tube formation assay, we found that UGCG could promote the proliferation, migration, and tube formation activity of HUVECs, whereas the inhibition of UGCG could inhibit the proliferation, migration, and tube formation activity of HUVECsTIE2-L914F. Finally, Western blotting revealed that UGCG regulates the AKT/mTOR pathway in HUVECs. These data demonstrated that UGCG can affect the activity of vascular endothelial cells and regulate the AKT/mTOR signaling pathway; this is a potential mechanism underlying VM pathogenesis.
Preparation of CsPb(Cl/Br)3/TiO2:Eu3+ composites for white light emitting diodes
Authors: Zhang Chen , Wang Minqiang , Shi Jindou , Wang Junnan , Da Zheyuan , Zhou Yun , Xu Youlong , Gaponenko Nikolai V. , Bhatti Arshad Saleem
Published: May 2023

The inherent single narrow emission peak and fast anion exchange process of cesium lead halide perovskite CsPbX3 (X = Cl, Br, I) nanocrystals severely limited its application in white light-emitting diodes. Previous studies have shown that composite structures can passivate surface defects of NCs and improve the stability of perovskite materials, but complex post-treatment processes commonly lead to dissolution of NCs. In this study, CsPb(Cl/Br)3 NCs was in-situ grown in TiO2 hollow shells doped with Eu3+ ions by a modified thermal injection method to prepare CsPb(Cl/Br)3/TiO2:Eu3+ composites with direct excitation of white light without additional treatment. Among them, the well-crystalline TiO2 shells acted as both a substrate for the dopant, avoiding the direct doping of Eu3+ into the interior of NCs to affect the crystal structure of the perovskite materials, and also as a protection layer to isolate the contact between PL quenching molecules and NCs, which significantly improves the stability. Further, the WLED prepared using the composites had bright white light emission, luminous efficiency of 87.39 lm/W, and long-time operating stability, which provided new options for the development of perovskite devices.
Nickel-phytic acid hybrid for highly efficient electrocatalytic upgrading of HMF
Authors: Liu Shuyi , Yuan Xue , Huang Xin , Huang Yu , Sun Chen , Qian Kun , Zhang Wenjie
Published: May 2023

Electrocatalytic upgrading of 5-hydroxymethylfurfural (HMF) provides a promising way to obtain both high-value-added biomass-derived chemicals and clean energy. However, development of efficient electrocatalysts for oxidizing HMF with depressed side reactions remains a challenge. Herein, we report a nickel-phytic acid hybrid (Ni-PA) using natural phytic acid as building block for highly efficient electrocatalytic oxidation of HMF to 2, 5-furandicarboxylic acid (FDCA). Due to the coordination of nickel ion and phosphate groups of phytic acid molecule, high selectivity and yield of FDCA were achieved at 1.6 V vs. RHE. Besides, Ni-PA has a higher electrochemical surface area and lower charge-transfer resistance than Cu/Fe-PA, which significantly promotes the oxidation of HMF to FDCA. This work demonstrates the potential of metal-phytic acid hybrids as effective electrocatalysts for biomass valorization.
Foodborne Parasites Dominate Current Parasitic Infections in Hunan Province, China
Authors: Liu Xiaohua , Wu Mengqi , Liu Yuan , Li Jing , Yang Dongqian , Jiang Liping
Published: May 2023

Great progress has been made in the prevention and treatment of human parasitic diseases in China over the past six decades, but parasitic diseases are still one of the most serious public health problems in the world. The specific prevalence of parasitic diseases varies in different provinces due to their geographical environment and the dietary habits of people. In this study, a total of 4,428 patients suspected to have parasitic infection by clinicians or themselves from January 1, 2016, to December 31, 2020 were recommended to our laboratory for further testing. In total, 5,246 samples including fecal, blood, and other body fluids were detected by etiological and immunological methods. Approximately 15.20% (673/4,428) of all suspected patients were infected by at least one species of parasite, and the overall positive rate of suspected patients from Hunan Province was 15.10% (594/3,933). A total of 18 species of parasites, namely, nematodes (4 species), trematodes (5 species), cestodes (4 species), protozoa (2 species), and medical arthropods (3 species), and 3 of them were imported parasites outside of Hunan Province. There are 9 species of foodborne parasites, accounting for 89.92% (464/516) of patients infected by one species of parasite. Common parasites in Hunan Province include plerocercoid, Paragonimus westermani, Clonorchis sinensis, cysticercus, Toxoplasma gondii, and Schistosoma japonicum. In this study, we found that the incidence of soilborne nematode infections has decreased significantly. However, foodborne parasites gradually become the main parasitic infections as well as multiple infections are becoming more common. Therefore, we should not only continue the prevention and control of soil-derived nematodes but also focus on the prevention and control of foodborne parasites in the future.
Comparison of long-term complications in cancer patients with incidental and acute symptomatic venous thromboembolism
Authors: Barca-Hernando María , Lopez-Ruz Sergio , Marin-Romero Samira , Elias-Hernandez Teresa , Otero-Candelera Remedios , Jara-Palomares Luis
Published: May 2023

Background

Clinical practice guidelines recommend that patients with incidental venous thromboembolism (VTE) receive the same anticoagulant therapy as those with symptomatic VTE. We aimed to compare the rate of complications between cancer patients with incidental and symptomatic VTE through a long-term follow-up cohort.

Methods

We performed a post hoc analysis of prospective studies of cancer patients with VTE between 2008 and 2019, with the primary outcome of rates of recurrent VTE and clinically relevant bleeding (CRB) in incidental and symptomatic VTE groups.

Results

In total, 796 patients were included, of which 42.8% had incidental VTE. No significant differences were noted in the rate of recurrent VTE (0.4 per 100 patients/month vs. 0.5 per 100 patients/month; p = 0.313) and in the rate of CRB (0.6 per 100 patients/month vs. 0.5 per 100 patients/month; p = 0.128) between patients with incidental VTE and symptomatic VTE, respectively. At six-month follow-ups, the cumulative incidence of CRB was significantly higher in patients with incidental VTE than that in those with symptomatic VTE (7.9% vs. 4.4%, respectively; OR: 1.8; 95% CI: 1.01–3.2).

Conclusion

Cancer patients with incidental VTE had similar rates of CRB and VTE recurrence in long-term follow-up compared with patients with symptomatic VTE. At six-month follow-ups, patients with incidental VTE had a higher cumulative incidence of CRB than those with symptomatic VTE.
Case report: A case of perinodal atrial tachycardia and review of the relevant clinical anatomy surrounding the retroaortic node
Authors: Raina Anvi , Tan Nicholas Y. , Fatunde Olubadewa A. , Asirvatham Samuel J. , DeSimone Christopher V.
Published: May 2023

A 70-year-old female presented with incessant supraventricular tachycardia that was refractory to metoprolol and sotalol. ECG revealed a narrow complex tachycardia with a rate of 163 beats per minute with a short RP relationship. She had salvos of atrial tachycardia which led to a severe reduction in ejection fraction as noted on echocardiography and hemodynamic instability. An electrophysiological study was performed, and findings suggested this to be an atrial tachycardia with earliest activation in the perinodal area. Radiofrequency ablation was carried out along the septum and associated structures to surround this region including the right atrium, non-coronary sinus of Valsalva, and the left atrium (anterior wall outside of the right superior pulmonary vein) to isolate this area and surround the focus with ablation lesions. The patient has done well post-procedure and continues to do well without any recurrence on low-dose flecainide at 8 months.
Cardiac sarcoidosis: a comprehensive review of risk factors, pathogenesis, diagnosis, clinical manifestations, and treatment strategies
Authors: Shah Hussain Haider , Zehra Syeda Alishah , Shahrukh Aliza , Waseem Radeyah , Hussain Tooba , Hussain Muhammad Sheheryar , Batool Fareeha , Jaffer Muhammad
Published: May 2023

Cardiac Sarcoidosis (CS) is a deadly consequence of systemic sarcoidosis that inflames all three layers of the heart, especially the myocardium—clinical signs of CS range from asymptomatic disease to abrupt cardiac death. CS generally remains undiagnosed secondary to a lack of definitive diagnostic criteria, a high percentage of false negative results on endomyocardial biopsy, and ill-defining clinical manifestations of the disease. Consequently, there is a lack of evidence-based recommendations for CS, and the present diagnostic and therapeutic management depend on expert opinion. The aetiology, risk factors, clinical symptoms, diagnosis, and therapy of CS will be covered in this review. A particular emphasis will be placed on enhanced cardiovascular imaging and early identification of CS. We review the emerging evidence regarding the use of Electrocardiograms (ECGs), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) imaging of the heart to identify and quantify the extent of myocardial inflammation, as well as to guide the use of immunotherapy and other treatment regimens, such as ablation therapy, device therapy, and heart transplantation, to improve patient outcomes.
Trends in unhealthy lifestyle factors in US NHANES respondents with cardiovascular disease for the period between 1999 and 2018
Authors: Liang Yanting , Liu Fengyao , Yin Han , Shi Xiaohe , Chen Yilin , Wang Haochen , Wang Yu , Bai Bingqing , Liu Yuting , Liu Quanjun , Wu Chao , Yu Xueju , Ma Huan , Geng Qingshan
Published: May 2023

Objectives

To examine national trends in unhealthy lifestyle factors among adults with cardiovascular disease (CVD) in the United States (US) between 1999 and 2018.

Methods

We analyzed data from National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of participants with CVD who were aged ≥20 years, which was conducted between 1999 and 2000 and 2017–2018. CVD was defined as a self-report of congestive heart failure, coronary heart disease, angina, heart attack, or stroke. The prevalence rate of each unhealthy lifestyle factor was calculated among adults with CVD for each of the 2-year cycle surveys. Regression analyses were used to assess the impact of sociodemographic characteristics (age, sex, race/ethnicity, family income, education level, marital status, and employment status).

Results

The final sample included 5610 NHANES respondents with CVD. The prevalence rate of their current smoking status remained stable among respondents with CVD between 1999 and 2000 and 2017–2018. During the same period, there was a decreasing trend in the age-adjusted prevalence rate of poor diet [primary American Heart Association (AHA) score <20; 47.5% (37.9%–57.0%) to 37.5% (25.7%–49.3%), p < 0.01]. Physical inactivity marginally increased before decreasing, with no statistical significance. The prevalence rate of sedentary behavior increased from 2007 to 2014 but subsequently returned to its original level in 2018 with no statistical significance. The age-adjusted prevalence rate of obesity increased from 32% (27.2%–36.8%) in 1999–2000 to 47.9% (39.9%–55.8%) in 2017–2018 (p < 0.001). The age-adjusted prevalence rate of depression increased from 7% (4.2%–9.9%) in 1999–2000 to 13.9% (10.2%–17.6%) in 2017–2018 (p = 0.056). Trends in mean for each unhealthy lifestyle factor were similar after adjustment for age. We found that respondents who had low education and income levels were at a higher risk of being exposed to unhealthy lifestyle factors (i.e., smoking, poor diet, and physical inactivity) than those who had high education and income levels.

Conclusions

There is a significant reduction in the prevalence rate of poor diet among US adults with CVD between 1999 and 2018, while the prevalence rate of obesity showed increasing trends over this period. The prevalence rate of current smoking status, sedentary behavior, and depression was either stable or showed an insignificant increase. These findings suggest that there is an urgent need for health policy interventions targeting unhealthy lifestyles among adults with CVD.
A case report of multiple artery pseudoaneurysms associated with SARS-CoV-2
Authors: Zhang Zixi , Xiao Yichao , Lin Qiuzhen , Liu Chan , Liu Qiming
Published: May 2023

Arterial pseudoaneurysms are rare vascular abnormalities that can occur as a complication of infections. Artery pseudoaneurysms associated with SARS-CoV-2 are a rare occurrence in COVID-19 patients, and their rupture can result in significant hemorrhage and sudden death. Few cases of SARS-CoV-2-associated artery pseudoaneurysms have been reported, and their underlying pathophysiological mechanisms remain unclear. This study presents the first reported case of a patient who developed both pulmonary and gallbladder artery pseudoaneurysms following SARS-CoV-2 infection. We investigate the potential pathogenesis of these pseudoaneurysms and aim to improve the understanding of this rare complication.
Distribution of harmful gas and ventilation length design of high altitude long gas tunnel construction: a case study
Authors: Zhang Xueqiang , Hu Juyi , Zhang Danfeng , Cai Shuang , Yang Feng
Published: May 2023

The air density in high altitude gas tunnel is small and the air supply is difficult. The jet tunnel ventilation is a common construction ventilation mode. In order to explore the pollutant distribution characteristics and the optimal ventilation length of tunnel ventilation in high altitude gas tunnel, Ningchan tunnel has been taken as the engineering background, the fluid dynamics software Fluent has been used to establish a three-dimensional model of jet tunnel ventilation, the distribution characteristics of methane, hydrogen sulfide and other harmful gas in the tunnel have been studied, and the optimal ventilation length of tunnel ventilation in high altitude gas tunnel degree has been explored. The results show that: the minimum ventilation length required in the existing technical specifications of gas tunnel is not reasonable, which leads to the existence of low-speed wind area in the tunnel, and harmful gas is easy to gather in the single head section, and the gas concentration can reach 0.59% at 2 m away from the working face; by reducing the ventilation length, the gas concentration in the single head section can be effectively reduced, and when the ventilation length is 1,200 m, the gas concentration at 2 m away from the working face will be reduced to 0.31%; setting local fan in front of the roadway can also significantly improve the accumulation degree of harmful gas in the single end section. The maximum gas concentration of working face reduced to 0.24%, and the average gas concentration of reduced to 0.15%. The results can provide reference for ventilation scheme of high altitude gas tunnel construction.
Processes of communication and dissemination of science: the challenges of science policy guidelines in Colombia
Authors: Niño-Sandoval Yaddy , Alvarez-Risco Aldo , Simbaqueba-Uribe John , Del-Aguila-Arcentales Shyla , Villalobos-Alvarez Diego , Yañez Jaime A.
Published: May 2023

Introduction

The present study aims to identify the characteristics of public policy relating to the Social Appropriation of Knowledge (SAK) in Colombia, generated between 2020 and 2021, on the communication and dissemination of science. Furthermore, the study aims to determine what incentives are offered by these policies to promote the communication and dissemination of science, and what importance is given to the use of digital scenarios.

Method

This is done through a comparative analysis of Colombia’s guidelines of public science policies using a bibliographical review.

Results and discussion

With this analysis, it is concluded that the policies resulting from 22 years of reflection in Colombia aim to strengthen the SAK in the communication of science, understood in specific relation to dissemination, which is understood as activities that make scientific knowledge accessible to a much wider audience.

Conclusion

The digital scenarios are proposed as communicative spaces to spread knowledge to communities and strengthen the science-society relationship.
Language skills and well-being in early childhood education and care: a cross-sectional exploration in a Swedish context
Authors: Riad Rasmus , Allodi Mara Westling , Siljehag Eva , Bölte Sven
Published: May 2023

Language skills play a vital role in academic achievement and support reading and writing acquisition. Language skills also enable children to interact with others and develop social abilities. Given the predictive value of early language skills for academic attainment and their connection to social interaction, they have been suggested to be an indicator of well-being as well. However, children from culturally and linguistically diverse backgrounds present lower scores than their peers with a majority language background on standardized language tests, such as vocabulary assessment. In the current study, we examined the relationship between language and self-reported well-being in the school context, based on data from a community sample of 85 five-year-old children attending eight preschools in three Swedish municipalities. Language skills were assessed through measures of vocabulary (receptive and expressive) and narrative skills (MAIN) and were analyzed using structural equation modeling. Narrative ability and vocabulary skills were correlated, but they appear to be distinct constructs. Exposure at home to the majority language was positively associated with vocabulary skills, while narrative ability was not strongly associated with language background. Language skills and well-being were not significantly correlated in the total sample, but post hoc analysis revealed that language background may affect the association. A novel contribution of this study is empirical data on language performance from a community sample with a large proportion of children with diverse language backgrounds. The relationship between subjective well-being and language skills warrants further investigation.
Effects of the in-utero dicyclohexyl phthalate and di-n-hexyl phthalate administration on the oxidative stress-induced histopathological changes in the rat liver tissue correlated with serum biochemistry and hematological parameters
Authors: Aydemir Duygu , Aydogan-Ahbab Mufide , Barlas Nurhayat , Ulusu Nuriye Nuray
Published: May 2023

Phthalates are widely used as plasticizers in the industry and are found in cosmetics, food and drink packaging, drugs, toys, households, medical devices, pesticides, personal care products, and paints. Phthalates exert endocrine disrupting and peroxisome proliferator effects in humans and wildlife associated with the pathogenesis of various diseases, including diabetes, obesity, infertility, cardiovascular diseases, metabolic syndrome, and cancer. Since phthalates are metabolized in the liver, which regulates the body’s energy metabolism, long or short-term exposure to the phthalates is associated with impaired glucose, lipid, and oxidative stress metabolisms contributing to liver toxicity. However, the impact of in-utero exposure to DHP and DCHP on liver metabolism has not been studied previously. Thus, in this study, we evaluated serum biochemistry parameters, hematological markers, histopathological changes, and oxidative and pentose phosphate pathway (PPP) metabolisms in the liver following in-utero DHP and DCHP administration, respectively, in male and female rats. We found increased relative and absolute liver weights and impaired triglyceride, alanine transaminase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels upon dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP). Histopathological changes, including congestion, sinusoidal dilatation, inflammatory cell infiltration, cells with a pyknotic nucleus, lysis of hepatocytes, and degeneration of hepatic parenchyma have been observed in the liver samples of DHP and DCHP dose groups. Moreover, increased glutathione s-transferase (GST), glucose 6-phosphate dehydrogenase (G6PD), and glutathione reductase (GR) activities have been found in the liver samples of DHP and DCHP-treated rats associated with impaired pentose phosphate pathway (PPP) and oxidative stress metabolism. First time in the literature, we showed that in-utero exposure to DHP and DCHP causes liver damage associated with impaired oxidative stress metabolism in male and female rats. Our data may guide researchers and governments to regulate and restrict phthalates in industrial products.
Klotho inversely relates with carotid intima- media thickness in atherosclerotic patients with normal renal function (eGFR ≥60 mL/min/1.73m2): a proof-of-concept study
Authors: Donate-Correa Javier , Martín-Núñez Ernesto , Martin-Olivera Alberto , Mora-Fernández Carmen , Tagua Víctor G. , Ferri Carla M. , López-Castillo Ángel , Delgado-Molinos Alejandro , López-Tarruella Victoria Castro , Arévalo-Gómez Miguel A. , Pérez-Delgado Nayra , González-Luis Ainhoa , Navarro-González Juan F.
Published: May 2023

Introduction

Klotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated.

Methods

We conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR≥60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry.

Results

APatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p<0.001), mRNA expression in blood circulating cells and carotid artery wall (2.92 [2.06-4.8] vs. 3.69 [2.42-7.13] log.a.u., p=0.015; 0.41 [0.16-0.59] vs. 0.79 [0.37-1.4] log.a.u., p=0.013, respectively) and immunoreactivity in the intimal-medial area of the carotids (4.23 [4.15-4.27] vs. 4.49 [4.28-4.63] log µm2 p=0.008). CIMT was inversely related with Klotho levels in serum (r= -0.717, p<0.001), blood mRNA expression (r=-0.426, p=0.011), and with carotid artery mRNA and immunoreactivity levels (r= -0.45, p=0.07; r= -0.455, p= 0.006, respectively). Multivariate analysis showed that serum Klotho, together with the gene expression levels of tumor necrosis factor TNFa in blood circulating cells, were independent determinants of CIMT values (adjusted R2 = 0.593, p<0.001).

Discussion

The results of this study in subjects with eGFR≥60mL/min/1.73m2 show that patients with carotid artery atherosclerosis and higher values of CIMT present reduced soluble Klotho levels, as well as decreased KL mRNA expression in peripheral blood circulating cells and Klotho protein levels in the intima-media of the carotid artery wall.
Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
Authors: Li Gerui , Li Hang , Chen Ze
Published: May 2023

Background

Immune cells play an integral role in the development and progression of non-alcoholic fatty liver disease (NAFLD). This study was to identify immune-cell-related biomarkers for the diagnosis and treatment of NAFLD.

Methods and findings

First, we introduced human liver transcriptome data from the GEO database (GSE48452 and GSE126848) and performed a weighted gene co-expression network analysis (WGCNA) to screen out the modules related to immune cell infiltration and to identify immune-cell-related differentially expressed genes (ICR-DEGs) associated with NAFLD progression. Further, the protein-protein interaction (PPI) network of ICR-DEGs was established to obtain hub genes and subsequently, the expression trend analysis was conducted to identify immune-cell-related biomarkers of NAFLD. Finally, the mRNA expression of biomarkers was validated in a NAFLD mouse model induced by high-fat diet (HFD) feeding. In total, we identified 66 ICR-DEGs and 13 hub genes associated with NAFLD. Among them, 9 hub genes (CD247, CD74, FCGR2B, IL2RB, INPP5D, MRPL16, RPL35, RPS3A, RPS8) were correlated with the infiltrating immune cells by the Pearson correlation analysis. Subsequently, 4 immune-cell-related biomarkers (RPL35, RPS3A, RPS8, and MRPL16) with the same expression trends in GSE48452 and GSE126848 datasets were identified. These biomarkers were enriched in immune-related pathways and had a good ability to distinguish between NASH and healthy samples. Moreover, we constructed a competing endogenous RNA (ceRNA) network of biomarkers and predicted twenty potential therapeutic drugs targeting RPS3A such as taxifolin and sitagliptin. Finally, experimental validation indicated that the hepatic mRNA expression of Rpl35, Rps3A, and Rps8 was significantly decreased in NAFLD mice.

Conclusions

This study identified four ribosomal protein genes (RPL35, RPS3A, RPS8, and MRPL16) as immune-cell-related biomarkers of NAFLD, which may actively participate in the immune processes during NAFLD progression and could serve as potential targets for the diagnosis and treatment of NAFLD.
Nexus between health poverty and climatic variability in Pakistan: a geospatial analysis
Authors: Khan Sami Ullah , Sheikh Muhammad Ramzan , Dimen Levente , Batool Hafsah , Abbas Asad , Nuta Alina Cristina
Published: May 2023

Studies investigating the interconnection of health poverty and climatic variability are rare in spatial perspectives. Given the importance of sustainable development goals 3, goal 10, and goal 13, we explored whether the geographic regions with diverse climate structure has a spatial association with health poverty; whether spatial disparities exist across districts of Pakistan. We implied the A-F methodology to estimate the MHP index using the PSLM survey, 2019–20. The climate variables were extracted from the online NASA website. We applied the spatial techniques of Moran’s I, univariate and bivariate LISA, to address the research questions. The findings revealed that the magnitude of MHP differs across districts. Punjab was found to be the better-ff whereas Baluchistan was the highest health poverty-stricken province. The spatial results indicated positive associations of MHP and climate indicators with their values in the neighbors, whereas a negative spatial association was found between the MHP and climate indicators. Also, spatial clusters and outliers of higher MHP were significant in Baluchistan and KP provinces. Government intervention and policymaker’s prioritization are needed towards health and health-related social indicators, mainly in the high poverty-stricken districts, with high temperature and low humidity and precipitation rates, especially in Baluchistan.
Disentangling the spread dynamics of insect invasions using spatial networks
Authors: Estay Sergio A. , Silva Carmen P. , López Daniela N. , Labra Fabio A.
Published: May 2023

Introduction

Describing and understanding spatiotemporal spread patterns in invasive species remains a long-standing interdisciplinary research goal. Here we show how a network-based top-down approach allows the efficient description of the ongoing invasion byDrosophila suzukiiin Chile.

Methods

To do so, we apply theoretical graph methods to calculate the minimum cost arborescence graph (MCA) to reconstruct and understand the invasion dynamics ofD. suzukiisince the first detection in 2017. This method estimates a directed rooted weighted graph by minimizing the total length of the resulting graph. To describe the temporal pattern of spread, we estimate three metrics of spread: the median dispersal rate, the median coefficient of diffusion, and the median dispersal acceleration.

Results

The estimated MCA shows that over four years,D. suzukiicolonized a ~1,000km long strip in the central valley of Chile, with an initial phase with long paths and connections and no clear direction pattern, followed by a clearer north–east propagation pattern. The median dispersal rate for the entire period was 8.8 (7.4–10.6, 95% CI), while the median diffusion coefficient was 19.6 meters2/day (13.6–27.9, 95% CI). The observed spread dynamics and the log-normal distribution of accelerations are consistent with long-distance dispersal events.

Discussion

The complexities of real landscapes cannot be summarized in any model, but this study shows how an alternative top-down approach based on graph theory can facilitate the ecological analysis of the spread of an invasive species in a new territory.
Deciphering the single-cell transcriptome network in keloids with intra-lesional injection of triamcinolone acetonide combined with 5-fluorouracil
Authors: Xia Yijun , Wang Youbin , Hao Yan , Shan Mengjie , Liu Hao , Liang Zhengyun , Kuang Xinwen
Published: May 2023

Objectives

Keloid is a highly aggressive fibrotic disease resulting from excessive extracellular matrix deposition after dermal injury. Intra-lesional injection of triamcinolone acetonide (TAC) in combination with 5-fluorouracil (5-FU) is a commonly used pharmacological regimen and long-term repeated injections can achieve sustained inhibition of keloid proliferation. However, the molecular mechanisms underlying the inhibitory effect on keloids remain insufficiently investigated.

Methods and materials

This study performed single-cell RNA sequencing analysis of keloids treated with TAC+5-FU injections, keloids, and skins to explore patterns of gene expression regulation and cellular reprogramming.

Results

The results revealed that TAC+5-FU interrupted the differentiation trajectory of fibroblasts toward pro-fibrotic subtypes and induced keloid atrophy possibly by inhibiting the FGF signaling pathway in intercellular communication. It also stimulated partial fibroblasts to develop the potential for self-replication and multidirectional differentiation, which may be a possible cellular source of keloid recurrence. T cell dynamics demonstrated elevated expression of secretory globulin family members, which may be possible immunotherapeutic targets. Schwann cell populations achieved functional changes by increasing the proportion of apoptotic or senescence-associated cell populations and reducing cell clusters that promote epidermal development and fibroblast proliferation.

Conclusions

Our findings elucidated the molecular and cellular reprogramming of keloids by intra-lesional injection of TAC+5-FU, which will provide new insights to understand the mechanism of action and therapeutic targets.
The circadian rhythm key gene ARNTL2: a novel prognostic biomarker for immunosuppressive tumor microenvironment identification and immunotherapy outcome prediction in human cancers
Authors: Wu Gujie , Ren Hefei , Hu Qin , Ma Huiyun , Chen Hongyu , Zhou Lin , Xu Kun , Ding Liang
Published: May 2023

Background

Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) belongs to the b HLH- PAS domain transcription factor family and is one of the key clock genes that control the circadian rhythm. ARNTL2 plays an important role in human biological functions. However, its role in various tumors, especially in the tumor immune microenvironment (TIME) and immunotherapy, remains unclear.

Methods

We integrated data from cancer patients from multiple databases, including the Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression, Human Protein Atlas, cBioPortal, TIMER, and ImmuCellAI, with data from a large clinical study, three immunotherapy cohorts, and in vitro experiments to investigate the involvement of ARNTL2 expression in cancer prognosis and immune response.

Results

ARNTL2 displayed abnormal expression within most malignant tumors, and is significantly associated with poorer survival and pathologic staging. Through gene-set enrichment analysis (GSEA) and gene-set variation analysis (GSVA), we found that ARNTL2 not only regulates cell cycle-related functions to promote cell proliferation but also regulates autoimmunity-related functions of the innate and adaptive immune systems, and other immune-related signaling pathways. In addition, ARNTL2 overexpression contributes to an immunosuppressive tumor microenvironment that plays a key role in immunosuppression-related features, such as the expression of immunosuppression-related genes and pathways and the number of immunosuppressive-infiltrating cells, including regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). The group of patients with low ARNTL2 expression who received immune checkpoint inhibitors (ICI) therapy had better response rates and longer survival when compared to those with high ARNTL2 expression.

Conclusion

The findings of this study suggest that ARNTL2 is a potential human oncogene that plays an important role in tumorigenesis and cancer immunity. Elevated ARNTL2 expression indicates an immunosuppressive tumor microenvironment. Targeting ARNTL2 in combination with ICI therapy could bring more significant therapeutic benefits to patients with cancer. Our study sheds light on the remarkable potential of ARNTL2 in tumor immunity and provides a novel perspective for anti-tumor strategies.
Transcriptome-wide identification of altered RNA m6A profiles in cardiac tissue of rats with LPS-induced myocardial injury
Authors: Wang Wei , Zhang Tie-Ning , Yang Ni , Wen Ri , Wang Yu-Jing , Zhang Bing-Lun , Yang Yu-Hang , Liu Chun-Feng
Published: May 2023

Purpose

Myocardial injury is a common complication in patients with endotoxaemia/sepsis, especially in children. Moreover, it develops through an unclear pathophysiological mechanism, and effective therapies are lacking. Recently, RNA modification, particularly N6-methyladenosine (m6A) modification, has been found to be involved in various physiological processes and to play important roles in many diseases. However, the role of m6A modification in endotoxaemia/sepsis-induced myocardial injury is still in its infancy. Therefore, we attempted to construct the m6A modification map of myocardial injury in a rat model treated by lipopolysaccharide (LPS) and explore the role of m6A modification in LPS-induced myocardial injury.

Method

Myocardial injury adolescent rat model was constructed by intraperitoneal injection of LPS. m6A RNA Methylation Quantification Kit was used to detect overall level of m6A modification in rat cardiac tissue. m6A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were conducted to identify the altered m6A-modified genes and differentially expressed genes in cardiac tissue of rats treated by LPS and control rats (6 versus. 6). Bioinformatics was used to analyze the functions of differentially m6A modified genes, differentially expressed genes, and genes with both differential m6A modification and differential expression. qPCR was used to detect expression of m6A modification related enzymes.

Result

We found that the overall level of m6A modification in cardiac tissue of the LPS group was up-regulated compared with that of the control group. MeRIP-seq and RNA-seq results showed that genes with differential m6A modification, genes with differential expression and genes with both differential m6A modification and differential expression were closely associated with inflammatory responses and apoptosis. In addition, we found that m6A-related enzymes (Mettl16, Rbm15, Fto, Ythdc2 and Hnrnpg) were differentially expressed in the LPS group versus. the control group.

Conclusion

m6A modification is involved in the pathogenesis process of LPS-induced myocardial injury, possibly through the regulation of inflammatory response and apoptosis-related pathways. These results provide valuable information regarding the potential pathogenic mechanisms underlying LPS-induced myocardial injury.
Immunometabolic reprogramming, another cancer hallmark
Authors: Kumar Vijay , Stewart John H.
Published: May 2023

Molecular carcinogenesis is a multistep process that involves acquired abnormalities in key biological processes. The complexity of cancer pathogenesis is best illustrated in the six hallmarks of the cancer: (1) the development of self-sufficient growth signals, (2) the emergence of clones that are resistant to apoptosis, (3) resistance to the antigrowth signals, (4) neo-angiogenesis, (5) the invasion of normal tissue or spread to the distant organs, and (6) limitless replicative potential. It also appears that non-resolving inflammation leads to the dysregulation of immune cell metabolism and subsequent cancer progression. The present article delineates immunometabolic reprogramming as a critical hallmark of cancer by linking chronic inflammation and immunosuppression to cancer growth and metastasis. We propose that targeting tumor immunometabolic reprogramming will lead to the design of novel immunotherapeutic approaches to cancer.
SIRT3 alleviates imiquimod-induced psoriatic dermatitis through deacetylation of XBP1s and modulation of TLR7/8 inducing IL-23 production in macrophages
Authors: Guo Meiliang , Zhuang Haojun , Su Yimin , Meng Qinqin , Liu Wanwen , Liu Na , Wei Min , Dai Sheng-Ming , Deng Hui
Published: May 2023

Current evidence suggests that IL-23, IL-6, and TNF-α play pivotal roles in the pathogenesis of psoriasis. Although it has been established that Sirtuin 3 (SIRT3) mediates the inflammatory process, the underlying mechanisms remain largely unclear. Herein, we substantiated that the inhibition or deletion of SIRT3 increased the acetylation level of spliced form of X-box binding protein 1 (XPB1s), enhancing its transcriptional activity and IL-23a production. Pharmacologically inhibition of XBP1s with MKC8866 downregulated the expression of inflammatory cytokines in SIRT3-inhibited or Sirt3-KO BMDMs stimulated by IMQ. Inhibition or knockdown of SIRT3 could exacerbate psoriasis-like skin inflammation in an imiquimod-induced psoriasis-like mouse model. Besides, a decrease in SIRT3 expression was observed in the macrophages of psoriasis patients, which increased the expression and acetylation level of XBP1s. Overall, we provide compelling evidence of the crucial role of SIRT3 in the IL-23 axis in psoriatic inflammation and novel molecular insights into the anti-inflammatory effects of SIRT3.
Bladder cancer patients have increased NETosis and impaired DNaseI-mediated NET degradation that can be therapeutically restored in vitro
Authors: Herranz Raquel , Oto Julia , Hueso Marta , Plana Emma , Cana Fernando , Castaño María , Cordón Lourdes , Ramos-Soler David , Bonanad Santiago , Vera-Donoso César D. , Martínez-Sarmiento Manuel , Medina Pilar
Published: May 2023

Background

Neutrophils, key players of the immune system, also promote tumor development through the formation of neutrophil extracellular traps (NETs) in a process called NETosis. NETs are extracellular networks of DNA, histones and cytoplasmic and granular proteins (calprotectin, myeloperoxidase, elastase, etc.) released by neutrophils upon activation. NETs regulate tumor growth while promoting angiogenesis and invasiveness, and tumor cells also stimulate NETosis. Although NETosis seems to be increased in cancer patients, an increase of NETs in plasma may also be mediated by an impaired degradation by plasma DNaseI, as evidenced in several immunological disorders like lupus nephritis. However, this has never been evidenced in bladder cancer (BC) patients. Herein, we aimed to evaluate the occurrence of increased NETosis in plasma and tumor tissue of BC patients, to ascertain whether it is mediated by a reduced DNaseI activity and degradation, and to in vitro explore novel therapeutic interventions.

Methods

We recruited 71 BC patients from whom we obtained a plasma sample before surgery and a formalin-fixed paraffin embedded tumor tissue sample, and 64 age- and sex-matched healthy controls from whom we obtained a plasma sample. We measured NETs markers (cell-free fDNA, calprotectin, nucleosomes and neutrophil elastase) and the DNaseI activity in plasma with specific assays. We also measured NETs markers in BC tissue by immunofluorescence. Finally, we evaluated the ability of BC and control plasma to degrade in vitro-generated NETs, and evaluated the performance of the approved recombinant human DNaseI (rhDNaseI, Dornase alfa, Pulmozyme®, Roche) to restore the NET-degradation ability of plasma. In vitro experiments were performed in triplicate. Statistical analysis was conducted with Graphpad (v.8.0.1).

Results

NETosis occurs in BC tissue, more profusely in the muscle-invasive subtype (P<0.01), that with the worst prognosis. Compared to controls, BC patients had increased NETosis and a reduced DNaseI activity in plasma (P<0.0001), which leads to an impairment to degrade NETs (P<0.0001). Remarkably, this can be therapeutically restored with rhDNaseI to the level of healthy controls.

Conclusion

To the best of our knowledge, this is the first report demonstrating that BC patients have an increased NETosis systemically and in the tumor microenvironment, in part caused by an impaired DNaseI-mediated NET degradation. Remarkably, this defect can be therapeutically restored in vitro with the approved Dornase alfa, thus Pulmozyme® could become a potential therapeutic tool to locally reduce BC progression.
Chronic ethanol exposure impairs alveolar leukocyte infiltration during pneumococcal pneumonia, leading to an increased bacterial burden despite increased CXCL1 and nitric oxide levels
Authors: Martins Flávia Rayssa Braga , de Oliveira Maycon Douglas , Souza Jéssica Amanda Marques , Queiroz-Junior Celso Martins , Lobo Francisco Pereira , Teixeira Mauro Martins , Malacco Nathalia Luisa , Soriani Frederico Marianetti
Published: May 2023

Ethanol abuse is a risk factor for the development of pneumonia caused by Streptococcus pneumoniae, a critical pathogen for public health. The aim of this article was to investigate the inflammatory mechanisms involved in pneumococcal pneumonia that may be associated with chronic ethanol exposure. Male C57BL6/J-Unib mice were exposed to 20% (v/v) ethanol for twelve weeks and intranasally infected with 5x104 CFU of S. pneumoniae. Twenty-four hours after infection, lungs, bronchoalveolar lavage and blood samples were obtained to assess the consequences of chronic ethanol exposure during infection. Alcohol-fed mice showed increased production of nitric oxide and CXCL1 in alveoli and plasma during pneumococcal pneumonia. Beside this, ethanol-treated mice exhibited a decrease in leukocyte infiltration into the alveoli and reduced frequency of severe lung inflammation, which was associated with an increase in bacterial load. Curiously, no changes were observed in survival after infection. Taken together, these results demonstrate that chronic ethanol exposure alters the inflammatory response during S. pneumoniae lung infection in mice with a reduction in the inflammatory infiltrate even in the presence of higher levels of the chemoattractant CXCL1.
Challenges and opportunities in vascularized composite allotransplantation of joints: a systematic literature review
Authors: Zhang Lei , Hoyos Isabel Arenas , Zubler Cédric , Rieben Robert , Constantinescu Mihai , Olariu Radu
Published: May 2023

Background

Joint allotransplantation (JA) within the field of vascularized composite allotransplantation (VCA) holds great potential for functional and non-prosthetic reconstruction of severely damaged joints. However, clinical use of JA remains limited due to the immune rejection associated with all forms of allotransplantation. In this study, we aim to provide a comprehensive overview of the current state of JA through a systematic review of clinical, animal, and immunological studies on this topic.

Methods

We conducted a systematic literature review in accordance with the PRISMA guidelines to identify relevant articles in PubMed, Cochrane Library, and Web of Science databases. The results were analyzed, and potential future prospects were discussed in detail.

Results

Our review included 14 articles describing relevant developments in JA. Currently, most JA-related research is being performed in small animal models, demonstrating graft survival and functional restoration with short-term immunosuppression. In human patients, only six knee allotransplantations have been performed to date, with all grafts ultimately failing and a maximum graft survival of 56 months.

Conclusion

Research on joint allotransplantation has been limited over the last 20 years due to the rarity of clinical applications, the complex nature of surgical procedures, and uncertain outcomes stemming from immune rejection. However, the key to overcoming these challenges lies in extending graft survival and minimizing immunosuppressive side effects. With the emergence of new immunosuppressive strategies, the feasibility and clinical potential of vascularized joint allotransplantation warrants further investigation.