bluuebunny/crossref_metadata_2025 huggingface dataset:
Gallstone disease and the risk of cardiac mortality in patients with acute coronary syndrome
Authors: Su Wen , Zhu Jie-Gao , Li Wei-Ping , Chen Hui , Li Hong-Wei
Published: November 2022

Background

Gallstone disease is a common gastrointestinal disorder, which has previously been reported to be associated with the incidence of cardiovascular disease. We aimed to investigate the association between gallstone disease and long-term outcomes in patients with acute coronary syndrome (ACS).

Materials and methods

A total of consecutive 13,975 ACS patients were included in this analysis. Gallstone disease in our study included both gallstones and cholecystectomy. The primary endpoint was cardiac mortality. The secondary outcome was all-cause mortality. Relative risks were estimated using Cox proportional hazards regression.

Results

During a median follow-up period of 2.96 years, 518 (4.2%) patients without gallstone disease and 62 (3.6%) patients in those with gallstone disease suffered cardiac death. After multivariable adjustment for established risk factors, subjects with gallstone disease had decreased risks of both cardiac mortality and all-cause mortality [hazard rate ratios (HR) = 0.72, 95% CI: 0.55–0.95 and HR = 0.75, 95% CI: 0.62–0.90, respectively]. In patients with performed cholecystectomy, the associations between gallstones and risks for cardiac mortality and all-cause mortality turned out to be non-significant. HRs varied across subgroups depending on the presence of selected established risk factors.

Conclusion

Presence of gallstone disease was associated with a significantly decreased risk of follow-up mortality in patients with ACS.
First hybrid implantations of novel Salus-Valves in patients with severe pulmonary regurgitation: A case series
Authors: Shao Zehua , Song Shubo , Han Yu , Liang Weijie , Fan Taibing
Published: November 2022

With the increasing age of patients after right ventricular outflow tract (RVOT) reconstruction, progressive pulmonary valve (PV) dysfunction can result in different degrees of right heart insufficiency, and PV replacement is frequently needed during follow-up. The traditional redo thoracotomy is difficult and associated with higher risks when compared to transcatheter implantations. Herein, we report the advantages and describe the outcomes of the first hybrid implantations of the novel Salus-Valves (Balance Medical, Beijing, China) from the sub-xiphoid approach in five patients (mean age of 22.6 years) with severe pulmonary regurgitation (PR) after RVOT reconstruction.
Gender-based time discrepancy in diagnosis of coronary artery disease based on data analytics of electronic medical records
Authors: Panahiazar Maryam , Bishara Andrew M. , Chern Yorick , Alizadehsani Roohallah , Islam Sheikh M. Shariful , Hadley Dexter , Arnaout Rima , Beygui Ramin E.
Published: November 2022

Background

Women continue to have worse Coronary Artery Disease (CAD) outcomes than men. The causes of this discrepancy have yet to be fully elucidated. The main objective of this study is to detect gender discrepancies in the diagnosis and treatment of CAD.

Methods

We used data analytics to risk stratify ~32,000 patients with CAD of the total 960,129 patients treated at the UCSF Medical Center over an 8 year period. We implemented a multidimensional data analytics framework to trace patients from admission through treatment to create a path of events. Events are any medications or noninvasive and invasive procedures. The time between events for a similar set of paths was calculated. Then, the average waiting time for each step of the treatment was calculated. Finally, we applied statistical analysis to determine differences in time between diagnosis and treatment steps for men and women.

Results

There is a significant time difference from the first time of admission to diagnostic Cardiac Catheterization between genders (p-value = 0.000119), while the time difference from diagnostic Cardiac Catheterization to CABG is not statistically significant.

Conclusion

Women had a significantly longer interval between their first physician encounter indicative of CAD and their first diagnostic cardiac catheterization compared to men. Avoiding this delay in diagnosis may provide more timely treatment and a better outcome for patients at risk. Finally, we conclude by discussing the impact of the study on improving patient care with early detection and managing individual patients at risk of rapid progression of CAD.
Vascular and hormonal interactions in the adrenal gland
Authors: Abdellatif Alaa B. , Fernandes-Rosa Fabio L. , Boulkroun Sheerazed , Zennaro Maria-Christina
Published: November 2022

Primary aldosteronism is the most common form of secondary arterial hypertension, due to excessive aldosterone production from the adrenal gland. Although somatic mutations have been identified in aldosterone producing adenoma, the exact mechanisms leading to increased cell proliferation and nodule formation remain to be established. One hypothesis is that changes in vascular supply to the adrenal cortex, due to phenomena of atherosclerosis or high blood pressure, may influence the morphology of the adrenal cortex, resulting in a compensatory growth and nodule formation in response to local hypoxia. In this review, we will summarize our knowledge on the mechanisms regulating adrenal cortex development and function, describe adrenal vascularization in normal and pathological conditions and address the mechanisms allowing the cross-talk between the hormonal and vascular components to allow the extreme tissue plasticity of the adrenal cortex in response to endogenous and exogenous stimuli. We will then address recent evidence suggesting a role for alterations in the vascular compartment that could eventually be involved in nodule formation and the development of primary aldosteronism.
Production of biodiesel and analysis of exhaust particulate emissions and metal concentration of lubricant oil of the compression ignition engine
Authors: Bhangwar Sajjad , Liaquat Ali Memon , Luhar Muhammad Ramzan , Abbasi Aijaz , Kumar Laveet , Rajput Umair Ahmed , Mastoi Sanaullah
Published: November 2022

In this research, biodiesel fuel is produced using potassium hydroxide (KOH) as a catalyst and methanol as a co-solvent through the transesterification process. The analysis of particulate matter emissions from a compression ignition (CI) engine with pure diesel fuel (D100), biodiesel-mixed (B30), and clove oil (CL3000 ppm) was carried out. The findings obtained revealed 5.27% reduction of particulate matter in biodiesel-blended fuel, and furthermore, when clove was added to the biodiesel-blended fuel, 11.61% reduction of particulate matter was observed as compared to pure diesel. It may be due to the higher oxygen ratio present in clove oil. The engine was run for 100 h on each fuel sample, and the data were taken and tested per 25 h for elemental analysis. The results manifest that the metal concentration found different elements in lubricant oil, i.e., lead (51.84), (24.89%), and (23.255%); copper (47.41%), (28.71%), and (23.86%); nickel (37.88%), (32.32), and (29.78%); and cadmium (46.12), (29.87%), and (24.01%) in diesel, biodiesel-blended fuel, and biodiesel blended with clove oil, respectively. This study found better results for engine life, which shows the lower metal concentration in biodiesel-blended fuel and clove oil than diesel. Furthermore, the fuels investigated in this research can reduce the wear of engine parts because biodiesel and clove oil contain a high oxygen ratio. Moreover, it has been found that biodiesel and clove oil as an antioxidant have a positive impact on noise emission levels for the CI engine.
Spatial distribution and influencing factors of mountainous geological disasters in southwest China: A fine-scale multi-type assessment
Authors: Shu Bo , Chen Yang , Amani-Beni Majid , Zhang Ruizhi
Published: November 2022

Abstract: Geological disasters have long been a constant threat to socioeconomic development and human life and property. Many studies focus on the occurred geological disasters and ignore the potential risk events. Fine-scale multi-type analysis of Potential Geological Disasters Spots (PGDSs) is a necessary but insufficiently explored research field in China’s mountainous areas. Taking Meigu County (Sichuan Province, Southwest China), a typical disaster-prone region, as the study area. Average nearest neighbor (ANN), standard deviational ellipse (SDE), kernel density estimation (KDE), and ordinary least squares (OLS) regression are used to assess the spatial distribution of potential geological disasters spots and their influencing factors. The findings show that: potential geological disasters spots have a significant spatial heterogeneity and exhibited a prominent clustering characteristic. They were distributed in an elevation range of 1,500–2000 m, which receives an average monthly rainfall of more than 240 mm, as well as in highly foliated (0.6 < Normalized Difference Vegetation Index (NDVI) < 0.8), west-facing (247.5–292.5°), and slopes of 10–20°. In addition, slope, aspect, population density, and rainfall were found as the main influencing factors. The results provide practical rural development measures with support for potential geological disasters spots avoidance and preparedness.
The impact of green urbanization on carbon emissions: The case of new urbanization in China
Authors: Li Yali , Gao Kangli
Published: November 2022

Urbanization in developing countries has brought economic growth and industrial development, but at the same time, it has also brought environmental problems, especially increased carbon emissions. Recently, China has promoted a new type of urbanization with the common goal of economic growth and green development, which provides a reference for the sustainable development of urbanization in developing countries. The study focuses on microscopic impact of this new urbanization on carbon emissions, which has received little attention previously. This study takes China as an example, constructs a quasi-natural experiment based on the first batch of new urbanization pilot areas in China, selects panel data of 164 prefecture-level cities from 2010–2019, applies the double difference method (DID) to identify the emission reduction effects of pilot policy on carbon emission (carbon emission intensity and per capita carbon emission), the mechanism of action model is constructed for further analysis, and various robustness tests are conducted. The results show that the new urbanization pilot policy can effectively diminish carbon emissions, and the sensitivity of pilot policy to per capita carbon emissions is greater than the intensity of carbon emissions, and the emission reduction effect of pilot policy of new urbanization tends to be enhanced with the implementation of pilot policy. With the improvement of infrastructure, the upgrading of advanced industrial structure, and the strengthening of environmental regulation, the inhibitory effect of new urbanization construction on carbon emissions tends to be enhanced. Various robustness tests show that green urbanization can effectively lessen carbon emissions, and under the constraint of economic growth rate target, if the government still gives priority to economic development, it is not conducive to the development of green urbanization. Therefore, the green urbanization process needs to be accelerated, infrastructure construction is linked, strict and appropriate environmental controls are adopted, the industrial layout is customized and the advanced industrial structure is promoted.
When less is more: Visitation by generalist pollinators can have neutral or negative effects on plant reproduction
Authors: Burns Cole , Villalobos Soraya , Vamosi Jana C.
Published: November 2022

Selection for specialized coevolutionary relationships can arise if generalized opportunistic pollinators, while still delivering some pollen, operate as less effective pollen delivery agents. Nevertheless, generalization could buffer high-latitude communities from loss of specialist pollinator species by providing some pollination service. Currently, there is limited understanding of the ecosystem services provided by generalized pollinators and whether they increase the fitness of the plants they visit. Network data and thorough observations of floral visitors, paired with estimates of seed set, offer some insight into the role of generalists, which in turn can inform us about how plants are likely to respond to ecosystem disturbances, such as losses of some pollinators, or changes in land cover. Here, we report on plant-pollinator visitation networks in Canada with high levels of generalization and examine the effects of generalization on seed set under different disturbance histories. We also then take a case study of one crop wild relative, Rubus arcticus or Arctic raspberry, and report on a near-complete characterization of pollinator interactions in different environmental conditions. Our findings indicate that generalized pollinators, though frequent and robust to variable temperatures and moisture conditions, do not appear to play a strong role in increasing the reproductive output of many plant species, and may provide only a weak buffer against the stronger effects of disturbance.
A process for change: The safe system approach and Vision Zero
Authors: Schell William J. , Ward Nicholas J.
Published: November 2022

While vision zero has been widely accepted as a core goal of many transportation agencies, to date efforts to achieve this target provide mixed results. One path to improved performance is gaining more interest in the United States-the safe system approach. While a safe system approach has proven successful in other countries and has great potential in the United States, successfully using this method requires a significant paradigm shift. Specifically, for many stakeholder organizations, establishing the safe system approach to reach Vision Zero represents a fundamental change in how they 1) perceive the road transport system, 2) interpret their role in that system, 3) operate with other system elements (stakeholder organizations), and 4) define a vision of success for the system. This level of transformative change requires structured preparation and deliberate management of the change process to be successful. In this paper we present a perspective on a process to initiate and manage this change that can increase the odds of success.
Clinical heterogeneity of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome in thirteen palestinian patients and report of a novel variant in the SLC25A15 gene
Authors: Dweikat Imad , Khalaf-Nazzal Reham
Published: November 2022

Background: Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome, is a rare autosomal recessive disorder characterized by impaired ornithine transport across the inner mitochondrial membrane. HHH is caused by biallelic disease-causing variants in the SLC25A15 gene. The clinical presentation of HHH is highly variable ranging from severe neonatal encephalopathy and hepatic failure to a milder form with corresponding learning difficulties.

Methods: In this study, data from thirteen patients with HHH syndrome, diagnosed between the age of 1 week–29 years at two tertiary care centers in Palestine, is presented. The clinical, biochemical, and molecular data are reviewed.

Results: Analysis of the SLC25A15 gene sequence revealed a novel homozygous frameshift deletion in exon 5, NM_014252.4:c.552-555delTTTC; p (Phe185SerfsTer8) in nine patients. The remaining four patients had a recurrent homozygous frameshift variant; NM_014252.4:c.446delG, (p.Ser149ThrfsTer45). The major acute clinical presentation found was encephalopathy and liver dysfunction. Nervous system involvement was common, progressive, and presented with signs of upper motor neuron disease as well as variable degrees of cognitive impairment. One patient had an initial presentation in adulthood with acute encephalopathy that responded well to treatment. There was no clear genotype-phenotype correlation.

Conclusion: Our results confirm the marked clinical heterogeneity of HHH including severe neonatal presentation, hepatic failure, and progressive pyramidal tract dysfunction in all age groups. The disease progression was variable, even in patients with the same genetic variant, and in patients with severe neonatal-onset hepatic encephalopathy. We report a novel pathogenic variant in the SLC25A15 gene, further expanding the molecular spectrum of the disease.
Exposure to endosulfan can cause long term effects on general biology, including the reproductive system of mice
Authors: Sharma Anju , Kaninathan Arigesavan , Dahal Sumedha , Kumari Susmita , Choudhary Bibha , Raghavan Sathees C.
Published: November 2022

Increased infertility in humans is attributed to the increased use of environmental chemicals in the last several decades. Various studies have identified pesticides as one of the causes of reproductive toxicity. In a previous study, infertility was observed in male mice due to testicular atrophy and decreased sperm count when a sublethal dose of endosulfan (3 mg/kg) with a serum concentration of 23 μg/L was used. However, the serum concentration of endosulfan was much higher (up to 500 μg/L) in people living in endosulfan-exposed areas compared to the one used in the investigation. To mimic the situation in an experimental setup, mice were exposed to 5 mg/kg body weight of endosulfan, and reproductive toxicity and long-term impact on the general biology of animals were examined. HPLC analysis revealed a serum concentration of ∼50 μg/L of endosulfan after 24 h endosulfan exposure affected the normal physiology of mice. Histopathological studies suggest a persistent, severe effect on reproductive organs where vacuole degeneration of basal germinal epithelial cells and degradation of the interstitial matrix were observed in testes. Ovaries showed a reduction in the number of mature Graafian follicles. At the same time, mild vacuolation in liver hepatocytes and changes in the architecture of the lungs were observed. Endosulfan exposure induced DNA damage and mutations in germ cells at the molecular level. Interestingly, even after 8 months of endosulfan exposure, we observed increased DNA breaks in reproductive tissues. An increased DNA Ligase III expression was also observed, consistent with reported elevated levels of MMEJ-mediated repair. Further, we observed the generation of tumors in a few of the treated mice with time. Thus, the study not only explores the changes in the general biology of the mice upon exposure to endosulfan but also describes the molecular mechanism of its long-term effects.
Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
Authors: Dai Lingling , Du Lizhong
Published: November 2022

Pulmonary arterial hypertension (PAH) is a rare but progressive and lethal vascular disease of diverse etiologies, mainly caused by proliferation of endothelial cells, smooth muscle cells in the pulmonary artery, and fibroblasts, which ultimately leads to right-heart hypertrophy and cardiac failure. Recent genetic studies of childhood-onset PAH report that there is a greater genetic burden in children than in adults. Since the first-identified pathogenic gene of PAH, BMPR2, which encodes bone morphogenetic protein receptor 2, a receptor in the transforming growth factor-β superfamily, was discovered, novel causal genes have been identified and substantially sharpened our insights into the molecular genetics of childhood-onset PAH. Currently, some newly identified deleterious genetic variants in additional genes implicated in childhood-onset PAH, such as potassium channels (KCNK3) and transcription factors (TBX4 and SOX17), have been reported and have greatly updated our understanding of the disease mechanism. In this review, we summarized and discussed the advances of genetic variants underlying childhood-onset PAH susceptibility and potential mechanism, and the most promising BMPR2 gene therapy and gene delivery approaches to treat childhood-onset PAH in the future.
Expression patterns of platinum resistance-related genes in lung adenocarcinoma and related clinical value models
Authors: Wang Zhe , Mu Lin , Feng He , Yao Jialin , Wang Qin , Yang Wenxiao , Zhou Huiling , Li Qinglin , Xu Ling
Published: November 2022

The purpose of this study was to explore platinum resistance-related biomarkers and mechanisms in lung adenocarcinoma. Through the analysis of gene expression data of lung adenocarcinoma patients and normal patients from The Cancer Genome Atlas, Gene Expression Omnibus database, and A database of genes related to platinum resistance, platinum resistance genes in lung adenocarcinoma and platinum resistance-related differentially expressed genes were obtained. After screening by a statistical significance threshold, a total of 252 genes were defined as platinum resistance genes with significant differential expression, of which 161 were up-regulated and 91 were down-regulated. The enrichment results of up-regulated gene Gene Ontology (GO) showed that TOP3 entries related to biological processes (BP) were double-strand break repair, DNA recombination, DNA replication, the down-regulated gene GO enriches the TOP3 items about biological processes (BP) as a response to lipopolysaccharide, muscle cell proliferation, response to molecule of bacterial origin. Gene Set Enrichment Analysis showed that the top three were e2f targets, g2m checkpoint, and rgf beta signaling. A prognostic model based on non-negative matrix factorization classification showed the characteristics of high- and low-risk groups. The prognostic model established by least absolute shrinkage and selection operator regression and risk factor analysis showed that genes such as HOXB7, NT5E, and KRT18 were positively correlated with risk score. By analyzing the differences in m6A regulatory factors between high- and low-risk groups, it was found that FTO, GPM6A, METTL3, and YTHDC2 were higher in the low-risk group, while HNRNPA2B1, HNRNPC, TGF2BP1, IGF2BP2, IGF2BP3, and RBM15B were higher in the high-risk group. Immune infiltration and drug sensitivity analysis also showed the gene characteristics of the platinum-resistant population in lung adenocarcinoma. ceRNA analysis showed that has-miR-374a-5p and RP6-24A23.7 were lower in the tumor expression group, and that the survival of the low expression group was worse than that of the high expression group. In conclusion, the results of this study show that platinum resistance-related differentially expressed genes in lung adenocarcinoma are mainly concentrated in biological processes such as DNA recombination and response to lipopolysaccharide. The validation set proved that the high-risk group of our prognostic model had poor survival. M6A regulatory factor analysis, immune infiltration, and drug sensitivity analysis all showed differences between high and low-risk groups. ceRNA analysis showed that has-miR-374a-5p and RP6-24A23.7 could be protective factors. Further exploration of the potential impact of these genes on the risk and prognosis of drug-resistant patients with lung adenocarcinoma would provide theoretical support for future research.
Tumor immune microenvironment in endometrial cancer of different molecular subtypes: evidence from a retrospective observational study
Authors: Dai Yibo , Zhao Luyang , Hua Dingchao , Cui Lina , Zhang Xiaobo , Kang Nan , Qu Linlin , Li Liwei , Li He , Shen Danhua , Wang Zhiqi , Wang Jianliu
Published: November 2022

Objective

Tumor immune microenvironmental features may predict survival and guide treatment. This study aimed to comprehensively decipher the immunological features of different molecular subtypes of endometrial cancer.

Methods

In this retrospective study, 26 patients with primary endometrial cancer and four with recurrent disease treated in our center from December 2018 to November 2021 were included. Next-generation sequencing was performed on tumor samples. Patients were classified into four subtypes, including POLE mutant, microsatellite instability high (MSI-H), no specific molecular profile (NSMP) and TP53 mutant subtypes. Tumor-infiltrating immune cells were quantified using multiplex immunofluorescence assays.

Results

Of the 26 primary endometrial cancer cases, three were POLE mutant, six were MSI-H, eight were NSMP and nine were TP53 mutant. Of the four recurrent cases, two belonged to the NSMP subtype and two belonged to the TP53 mutant subtype. The tumor mutation burden (TMB) levels of POLE mutant and MSI-H cases were significantly higher than that of the other two subtypes (p< 0.001). We combined POLE mutant and MSI-H subtypes into the TMB high (TMB-H) subtype. The TMB-H subtype showed a high degree of infiltration of CD8+ T cells. In the NSMP subtype, the overall degree of intra-tumoral infiltrating immune cells was low. In the TP53 mutant subtype, the densities of both PD-L1+ macrophages (p = 0.047) and PD-1+ T cells (p = 0.034) in tumor parenchyma were the highest among the four subtypes.

Conclusion

Endometrial cancer of TMB-H, NSMP and TP53 mutant subtypes displayed phenotypes of normal immune response, absence of immune infiltration, and suppressed immune response, respectively. These features may provide mechanistic explanations for the differences in patients’ prognosis and efficacy of immune checkpoint blockade therapies among different endometrial cancer subtypes.
Recent developments in PD-1/PD-L1 blockade research for gastroesophageal malignancies
Authors: Chen Meng , Li Chenyan , Sun Mingjun , Li Yiling , Sun Xuren
Published: November 2022

Gastroesophageal cancers (GECs) comprise malignancies in the stomach, esophagus, and gastroesophageal junction. Despite ongoing improvements in chemoradiotherapy, the clinical outcomes of GEC have not significantly improved over the years, and treatment remains challenging. Immune checkpoint inhibitors (ICIs) have been the subject of clinical trials worldwide for several years. Encouraging results have been reported in different countries, but further research is required to apply ICIs in the clinical care of patients with GEC. This review summarizes completed and ongoing clinical trials with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blockers in GEC and current biomarkers used for predicting PD-1/PD-L1 blockade efficacy. This review captures the main findings of PD-1/PD-L1 antibodies combined with chemotherapy as an effective first-line treatment and a monotherapy in second-line or more treatment and in maintenance therapy. This review aims to provide insight that will help guide future research and clinical trials, thereby improving the outcomes of patients with GEC.
PD-L1: Biological mechanism, function, and immunotherapy in gastric cancer
Authors: Zhang Yingzi , Yang Yan , Chen Yiran , Lin Wu , Chen Xiangliu , Liu Jin , Huang Yingying , Wang Haiyong , Teng Lisong
Published: November 2022

Gastric cancer (GC) is one of the main causes of cancer incidence rate and mortality worldwide. As the main breakthrough direction, the application of immune checkpoint inhibitors makes patients with GC have better prognosis, where PD-L1/PD-1 inhibitors in immunotherapy have good anti-tumor immune efficacy. Further understanding of the regulatory mechanism of PD-L1 in GC may bring substantial progress to the immunotherapy. In this review, we provide information on the endogenous and exogenous regulatory mechanisms of PD-L1 and its biological functions combined with current clinical trials of PD-L1/PD-1 inhibitors in GC. The malignant biological phenotypes caused by PD-L1 and the corresponding clinical combined treatment scheme have been reported. Identifying the biomarkers of the potential efficacy of immunotherapy and specifying the clinical immunotherapy scheme in combination with molecular characteristics of patients may maximize clinical benefits and better prognosis.
Determining distinct roles of IL-1α through generation of an IL-1α knockout mouse with no defect in IL-1β expression
Authors: Malireddi R.K. Subbarao , Bynigeri Ratnakar R. , Kancharana Balabhaskararao , Sharma Bhesh Raj , Burton Amanda R. , Pelletier Stephane , Kanneganti Thirumala-Devi
Published: November 2022

Interleukin 1α (IL-1α) and IL-1β are the founding members of the IL-1 cytokine family, and these innate immune inflammatory mediators are critically important in health and disease. Early studies on these molecules suggested that their expression was interdependent, with an initial genetic model of IL-1α depletion, the IL-1α KO mouse (Il1a-KOline1), showing reduced IL-1β expression. However, studies using this line in models of infection and inflammation resulted in contrasting observations. To overcome the limitations of this genetic model, we have generated and characterized a new line of IL-1α KO mice (Il1a-KOline2) using CRISPR-Cas9 technology. In contrast to cells fromIl1a-KOline1, where IL-1β expression was drastically reduced, bone marrow-derived macrophages (BMDMs) fromIl1a-KOline2mice showed normal induction and activation of IL-1β. Additionally,Il1a-KOline2BMDMs showed normal inflammasome activation and IL-1β expression in response to multiple innate immune triggers, including both pathogen-associated molecular patterns and pathogens. Moreover, usingIl1a-KOline2cells, we confirmed that IL-1α, independent of IL-1β, is critical for the expression of the neutrophil chemoattractant KC/CXCL1. Overall, we report the generation of a new line of IL-1α KO mice and confirm functions for IL-1α independent of IL-1β. Future studies on the unique functions of IL-1α and IL-1β using these mice will be critical to identify new roles for these molecules in health and disease and develop therapeutic strategies.
Sirtuins: Key players in obesity-associated adipose tissue remodeling
Authors: Chen Jiali , Lou Ruohan , Zhou Fei , Li Dan , Peng Cheng , Lin Ligen
Published: November 2022

Obesity, a complex disease involving an excessive amount of body fat and a major threat to public health all over the world, is the determining factor of the onset and development of metabolic disorders, including type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease. Long-term overnutrition results in excessive expansion and dysfunction of adipose tissue, inflammatory responses and over-accumulation of extracellular matrix in adipose tissue, and ectopic lipid deposit in other organs, termed adipose tissue remodeling. The mammalian Sirtuins (SIRT1–7) are a family of conserved NAD+-dependent protein deacetylases. Mounting evidence has disclosed that Sirtuins and their prominent substrates participate in a variety of physiological and pathological processes, including cell cycle regulation, mitochondrial biogenesis and function, glucose and lipid metabolism, insulin action, inflammatory responses, and energy homeostasis. In this review, we provided up-to-date and comprehensive knowledge about the roles of Sirtuins in adipose tissue remodeling, focusing on the fate of adipocytes, lipid mobilization, adipose tissue inflammation and fibrosis, and browning of adipose tissue, and we summarized the clinical trials of Sirtuin activators and inhibitors in treating metabolic diseases, which might shed light on new therapeutic strategies for obesity and its associated metabolic diseases.
Comparative analysis of marine-protected area effectiveness in the protection of marine mammals: Lessons learned and recommendations
Authors: Grau Tomás Estela , García Sanabria Javier
Published: November 2022

The aim of this study is to assess marine-protected areas’ (MPAs) effectiveness in the protection of marine mammals. With this purpose, the study analyzed the long-term population trend of four different species of marine mammals, geographically placed in distant MPAs. In addition, matching biophysical and governance indicators were identified in order to relate the different management approaches to the biological effectiveness or ineffectiveness of the respective MPA. The results show population recovery trends, providing empirical evidence that suggests the effectiveness of area-based protection measures in marine mammals. Moreover, a parallelism between the governance indicators and the biophysical ones supports that biological and management effectiveness are interrelated. On this basis, the biophysical indicator of human impact was discussed to be deeply related to the precautionary principle, which appears less efficient than the adaptive management. Finally, this study highlights the necessity to better monitor the effectiveness of MPAs in order to avoid paper parks and suggest future recommendations.
Clinical analysis of 45 cases of perforation were identified during endoscopic retrograde cholangiopancreatography procedure
Authors: Miao Yin-Shui , Li Yuan-Yuan , Cheng Bo-Wen , Zhan Yan-Fang , Zeng Sheng , Zhou Xiao-Jiang , Chen You-Xiang , Lv Nong-Hua , Li Guo-Hua
Published: November 2022

Background

Endoscopic retrograde cholangiopancreatography (ERCP) has become an important method to diagnose and treat biliary-pancreatic diseases. Perforations are infrequent but serious complications can occur during ERCPs. However, it is unclear which patients are suitable for surgery and when these patients should receive surgery.

Aim

To analyze the outcome of 45 patients with endoscopic retrograde cholangiopancreatography (ERCP) related perforation.

Materials and methods

We retrospectively reviewed all 45 patients with ERCP-related perforation between January 2003 and December 2017, and observed the location and causes of perforation, treatment strategies, and mortality.

Results

Twenty thousand four hundred and seventy-nine patients received ERCP procedures from January 2003 to December 2017 in our digestive endoscopy center. Forty-five patients suffered from ERCP-related perforations. The incidence rate of ERCP-related perforations was 0.22%. Twenty-six patients suffered from periampullary perforations, 15 patients suffered from duodenal wall perforations, 1 patient suffered from a fundus perforation, 1 patient suffered from a residual gallbladder duct perforation, 1 patient suffered from a papillary diverticulum perforation, and 1 patient suffered from an intrahepatic bile duct perforation. Six patients with duodenal perforations underwent surgery, and the other patients received conservative treatment. One patient with a duodenal perforation and ERCP-related pancreatitis died of heart failure, and all the other patients recovered. The mortality rate was 2.2%.

Conclusion

Endoscopic closure is seen as the first method for treating Stapfer type I perforations in the early phase, and surgery is seen as a remedial method when local treatment was failed. The Stapfer type II to type IV perforations can recover by conservative treatment.
Development of curative therapies for sickle cell disease
Authors: Tanhehco Yvette C. , Nathu Ghazala , Vasovic Ljiljana V.
Published: November 2022

Recent advances in managing Sickle Cell Disease (SCD) significantly improved patient survival and quality of life. Disease-modifying drug therapies such as hydroxyurea, L-glutamine, voxelotor, and crizanlizumab reduce pain crises and severe complications. Allogeneic hematopoietic stem cell transplantation using matched-sibling donors is currently the only standard curative option; however, only a small proportion of patients have such donors. Cord blood and haploidentical transplantation with a modified conditioning regimen have expanded the allogeneic donor pool, making the therapy available to more patients. Gene therapy is a promising cure that is currently undergoing clinical trials and different approaches have demonstrated efficacy. Multidisciplinary expertise is needed in developing the best treatment strategy for patients with SCD.
A fluorescently labelled quaternary ammonium compound (NBD-DDA) to study resistance mechanisms in bacteria
Authors: Nordholt Niclas , O'Hara Kate , Resch-Genger Ute , Blaskovich Mark A. T. , Rühle Bastian , Schreiber Frank
Published: November 2022

Quaternary ammonium compounds (QACs) are widely used as active agents in disinfectants, antiseptics, and preservatives. Despite being in use since the 1940s, there remain multiple open questions regarding their detailed mode-of-action and the mechanisms, including phenotypic heterogeneity, that can make bacteria less susceptible to QACs. To facilitate studies on resistance mechanisms towards QACs, we synthesized a fluorescent quaternary ammonium compound, namely N-dodecyl-N,N-dimethyl-[2-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]ethyl]azanium-iodide (NBD-DDA). NBD-DDA is readily detected by flow cytometry and fluorescence microscopy with standard GFP/FITC-settings, making it suitable for molecular and single-cell studies. As a proof-of-concept, NBD-DDA was then used to investigate resistance mechanisms which can be heterogeneous among individual bacterial cells. Our results reveal that the antimicrobial activity of NBD-DDA against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa is comparable to that of benzalkonium chloride (BAC), a widely used QAC, and benzyl-dimethyl-dodecylammonium chloride (BAC12), a mono-constituent BAC with alkyl-chain length of 12 and high structural similarity to NBD-DDA. Characteristic time-kill kinetics and increased tolerance of a BAC tolerant E. coli strain against NBD-DDA suggest that the mode of action of NBD-DDA is similar to that of BAC. As revealed by confocal laser scanning microscopy (CLSM), NBD-DDA is preferentially localized to the cell envelope of E. coli, which is a primary target of BAC and other QACs. Leveraging these findings and NBD-DDA‘s fluorescent properties, we show that reduced cellular accumulation is responsible for the evolved BAC tolerance in the BAC tolerant E. coli strain and that NBD-DDA is subject to efflux mediated by TolC. Overall, NBD-DDA’s antimicrobial activity, its fluorescent properties, and its ease of detection render it a powerful tool to study resistance mechanisms of QACs in bacteria and highlight its potential to gain detailed insights into its mode-of-action.
Food origin influences microbiota and stable isotope enrichment profiles of cold-adapted Collembola (Desoria ruseki)
Authors: Hao Cao , de Jonge Nadieh , Zhu Dong , Feng Lichao , Zhang Bing , Chen Ting-Wen , Wu Donghui , Nielsen Jeppe Lund
Published: November 2022

Collembola are a group of globally distributed microarthropods that can tolerate low temperature and are active in extremely cold environments. While it is well known that animal diets can shape their microbiota, the microbiota of soil animals is not well described, particularly for animals with limited food resources, such as Collembola active in winter at low temperatures. In this study, we explored the effects of three different food sources; corn litter (agriculture grain residuals), Mongolian oak litter (natural plant residuals), and yeast (common food for Collembola culture), on the microbiota of a winter-active Collembola species, Desoria ruseki. We found that microbial diversity and community composition of the Collembola were strongly altered after feeding with different food sources for 30 days. Collembola individuals fed on corn litter harbored the highest bacterial richness and were dominated by a representative of Microbacteriaceae. In contrast, those fed on yeast exhibited the lowest bacterial richness and were primarily colonized by Pseudomonas. The microbial communities associated with the winter-active Collembola differed significantly from those observed in the food. Collembola nutrient turnover also differed when cultured with different food sources, as indicated by the C and N stable isotopic signatures. Our study highlights microbial associations with stable isotopic enrichments of the host. Specifically, the Arthrobacter was positively correlated with δ13C enrichment in the host. Representatives of Microbacteriaceae, Micrococcaceae, TM7a, Devosia, and Rathayibacter were positively correlated with δ15N enrichment of the host. Our study indicates that food sources are major determinants for Collembola microbiota that simultaneously alter consumers’ isotopic niches, thereby improving our understanding of the roles played by host-microbiota interactions in sustaining soil biodiversity during the winter.
Persistent viral infections and their role in heart disease
Authors: Badrinath Ashwin , Bhatta Sagar , Kloc Anna
Published: November 2022

Viral infections are the culprit of many diseases, including inflammation of the heart muscle, known as myocarditis. Acute myocarditis cases have been described in scientific literature, and viruses, such as parvovirus B19, coxsackievirus B3, or more recently, SARS-CoV-2, were the direct cause of cardiac inflammation. If not treated, myocarditis could progress to dilated cardiomyopathy, which permanently impairs the heart and limits a person’s lifespan. Accumulated evidence suggests that certain viruses may persist in cardiac tissue after the initial infection, which could open up the door to reactivation under favorable conditions. Whether this chronic infection contributes to, or initiates, cardiac damage over time, remains a pressing issue in the field of virus-induced heart pathology, and it is directly tied to patients’ treatment. Previously, large case studies found that a few viruses: parvovirus B19, coxsackievirus, adenovirus, human herpesvirus 6, cytomegalovirus and Epstein–Barr virus, are most commonly found in human endomyocardial biopsy samples derived from patients experiencing cardiac inflammation, or dilated cardiomyopathy. SARS-CoV-2 infection has also been shown to have cardiovascular consequences. This review examines the role of viral persistence in cardiac inflammation and heart disease, and discusses its implications for patients’ outcomes.
P53 maintains gallid alpha herpesvirus 1 replication by direct regulation of nucleotide metabolism and ATP synthesis through its target genes
Authors: Xu Li , Chen Zhijie , Zhang Yu , Cui Lu , Liu Zheyi , Li Xuefeng , Liu Shengwang , Li Hai
Published: November 2022

P53, a well-known tumor suppressor, has been confirmed to regulate the infection of various viruses, including chicken viruses. Our previous study observed antiviral effect of p53 inhibitor Pifithrin-α (PFT-α) on the infection of avian infectious laryngotracheitis virus (ILTV), one of the major avian viruses economically significant to the poultry industry globally. However, the potential link between this antiviral effect of PFT-α and p53 remains unclear. Using chicken LMH cell line which is permissive for ILTV infection as model, we explore the effects of p53 on ILTV replication and its underlying molecular mechanism based on genome-wide transcriptome analysis of genes with p53 binding sites. The putative p53 target genes were validated by ChIP-qPCR and RT-qPCR. Results demonstrated that, consistent with the effects of PFT-α on ILTV replication we previously reported, knockdown of p53 repressed viral gene transcription and the genome replication of ILTV effectively. The production of infectious virions was also suppressed significantly by p53 knockdown. Further bioinformatic analysis of genes with p53 binding sites revealed extensive repression of these putative p53 target genes enriched in the metabolic processes, especially nucleotide metabolism and ATP synthesis, upon p53 repression by PFT-α in ILTV infected LMH cells. Among these genes, eighteen were involved in nucleotide metabolism and ATP synthesis. Then eight of the 18 genes were selected randomly for validations, all of which were successfully identified as p53 target genes. Our findings shed light on the mechanisms through which p53 controls ILTV infection, meanwhile expand our knowledge of chicken p53 target genes.
Impact of frequency of application on the long-term efficacy of the biocontrol product Aflasafe in reducing aflatoxin contamination in maize
Authors: Atehnkeng Joseph , Ojiambo Peter S. , Ortega-Beltran Alejandro , Augusto Joao , Cotty Peter J. , Bandyopadhyay Ranajit
Published: November 2022

Aflatoxins, produced by severalAspergillussectionFlavispecies in various crops, are a significant public health risk and a barrier to trade and development. In sub-Saharan Africa, maize and groundnut are particularly vulnerable to aflatoxin contamination. Aflasafe, a registered aflatoxin biocontrol product, utilizes atoxigenicA. flavusgenotypes native to Nigeria to displace aflatoxin producers and mitigate aflatoxin contamination. Aflasafe was evaluated in farmers’ fields for 3 years, under various regimens, to quantify carry-over of the biocontrol active ingredient genotypes. Nine maize fields were each treated either continuously for 3 years, the first two successive years, in year 1 and year 3, or once during the first year. For each treated field, a nearby untreated field was monitored. Aflatoxins were quantified in grain at harvest and after simulated poor storage. Biocontrol efficacy and frequencies of the active ingredient genotypes decreased in the absence of annual treatment. Maize treated consecutively for 2 or 3 years had significantly (p < 0.05) less aflatoxin (92% less) in grain at harvest than untreated maize. Maize grain from treated fields subjected to simulated poor storage had significantly less (p < 0.05) aflatoxin than grain from untreated fields, regardless of application regimen. Active ingredients occurred at higher frequencies in soil and grain from treated fields than from untreated fields. The incidence of active ingredients recovered in soil was significantly correlated (r = 0.898;p < 0.001) with the incidence of active ingredients in grain, which in turn was also significantly correlated (r = −0.621,p = 0.02) with aflatoxin concentration. Although there were carry-over effects, caution should be taken when drawing recommendations about discontinuing biocontrol use. Cost–benefit analyses of single season and carry-over influences are needed to optimize use by communities of smallholder farmers in sub-Saharan Africa.
Biochar improved the composting quality of seaweeds and cow manure mixture and altered the microbial community
Authors: Jia Haijiang , Chu Depeng , You Xiangwei , Li Yiqiang , Huang Chongjun , Zhang Jili , Zeng Xiangnan , Yao Hui , Zhou Zhaofeng
Published: November 2022

The beneficial effects of biochar addition during composting have been proved for many feedstocks, like manures and crop straws. However, the effect of biochar on the quality of composting product with seaweed as the feedstock and the bacterial response has not been investigated. In this study, the wheat straw biochar addition on the quality of the composting product and the bacterial response was explored at the rate of 0–10%. The results showed that biochar addition at the optimal rate (5%, w/w) could increase the germination index and the ratio of the optical density of humic acid at 460 nm to that at 660 nm (E4/E6) of the composting product, which indicated the decreased biotoxicity and enhanced compost maturity. The significant increase of the nitrate nitrogen (NO3−-N) content of the composting product proved the improvement of N cycling during composting process with biochar addition. The bacterial community of composting product was shifted and the relative abundance of some beneficial taxa (e.g., Muricauda and Woeseia) was significantly increased with biochar addition. Furthermore, the relative abundance of some bacterial genes related to amino acid metabolism and carbohydrate metabolism was also increased with biochar addition. The results of our study provided the positive effect of biochar addition on the composting of seaweed and could help to produce high quality seaweed fertilizer by composting with biochar addition.