bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of endoplasmic reticulum autophagy in acute lung injury
Authors: Liu Shiping , Fang Xiaoyu , Zhu Ruiyao , Zhang Jing , Wang Huijuan , Lei Jiaxi , Wang Chaoqun , Wang Lu , Zhan Liying
Published: May 2023

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), the prime causes of morbidity and mortality in critically ill patients, are usually treated by general supportive treatments. Endoplasmic reticulum autophagy (ER-phagy) maintains cellular homeostasis by degrading damaged endoplasmic reticulum (ER) fragments and misfolded proteins. ER-phagy is crucial for maintaining ER homeostasis and improving the internal environment. ER-phagy has a particular role in some aspects, such as immunity, inflammation, cell death, pathogen infection, and collagen quality. In this review, we summarized the definition, epidemiology, and pathophysiology of ALI/ARDS and described the regulatory mechanisms and functions of ER-phagy as well as discussed the potential role of ER-phagy in ALI/ARDS from the perspectives of immunity, inflammation, apoptosis, pathogen infection, and fibrosis to provide a novel and effective target for improving the prognosis of ALI/ARDS.
Diagnostic model constructed by five EMT-related genes for renal fibrosis and reflecting the condition of immune-related cells
Authors: Guo Yangyang , Yuan Ziwei , Hu Zujian , Gao Yuanyuan , Guo Hangcheng , Zhu Hengyue , Hong Kai , Cen Kenan , Mai Yifeng , Bai Yongheng , Yang Xuejia
Published: May 2023

Background

Renal fibrosis is a physiological and pathological characteristic of chronic kidney disease (CKD) to end-stage renal disease. Since renal biopsy is the gold standard for evaluating renal fibrosis, there is an urgent need for additional non-invasive diagnostic biomarkers.

Methods

We used R package “limma” to screen out differently expressed genes (DEGs) based on Epithelial-mesenchymal transformation (EMT), and carried out the protein interaction network and GO, KEGG enrichment analysis of DEGs. Secondly, the least absolute shrinkage and selection operator (LASSO), random forest tree (RF), and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to identify candidate diagnostic genes. ROC curves were plotted to evaluate the clinical diagnostic value of these genes. In addition, mRNA expression levels of candidate diagnostic genes were analyzed in control samples and renal fibrosis samples. CIBERSORT algorithm was used to evaluate immune cells level. Additionally, gene set enrichment analysis (GSEA) and drug sensitivity were conducted.

Results

After obtaining a total of 24 DEGs, we discovered that they were mostly involved in several immunological and inflammatory pathways, including NF-KappaB signaling, AGE-RAGE signaling, and TNF signaling. Five genes (COL4A2, CXCL1, TIMP1, VCAM1, and VEGFA) were subsequently identified as biomarkers for renal fibrosis through machine learning, and their expression levels were confirmed by validation cohort data sets and in vitro RT-qPCR experiment. The AUC values of these five genes demonstrated significant clinical diagnostic value in both the training and validation sets. After that, CIBERSORT analysis showed that these biomarkers were strongly associated with immune cell content in renal fibrosis patients. GSEA also identifies the potential roles of these diagnostic genes. Additionally, diagnostic candidate genes were found to be closely related to drug sensitivity. Finally, a nomogram for diagnosing renal fibrosis was developed.

Conclusion

COL4A2, CXCL1, TIMP1, VCAM1, and VEGFA are promising diagnostic biomarkers of tissue and serum for renal fibrosis.
Analysis and comparison of SARS-CoV-2 variant antibodies and neutralizing activity for 6 months after a booster mRNA vaccine in a healthcare worker population
Authors: Hosseinian Sina , de Assis Rafael , Khalil Ghali , Luu Madeleine K. , Jain Aarti , Horvath Peter , Nakajima Rie , Palma Anton M. , Hoang Anthony , Razzak Eisa , Garcia Nicholas , Alger Joshua , Kalantari Mina , Silzel Emily K. , Jasinskas Algis , Zaldivar Frank , Schubl Sebastian D. , Felgner Philip L. , Khan Saahir
Published: May 2023

Introduction

In the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination.

Methods

To characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray.

Results

The primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine based on the original Wuhan strain generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the vaccine strain. Despite waning antibody levels, neutralization activity against the vaccine strain is maintained throughout the 6-month period.

Discussion

In the context of recurrent surges of SARS-CoV-2 infections, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.
Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis
Authors: Cao Huanhuan , Huang Yufei , Zhong Chunxiu , Liao Xingmei , Tan Wenjuan , Zhao Siru , Guo Liangxu , Fan Rong
Published: May 2023

Background

The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis.

Patients and methods

A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire.

Results

A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001).

Conclusion

Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.
Gasdermins assemble; recent developments in bacteriology and pharmacology
Authors: Greenwood Claudine S. , Wynosky-Dolfi Meghan A. , Beal Allison M. , Booty Lee M.
Published: May 2023

The discovery of gasdermin D (GSDMD) as the terminal executioner of pyroptosis provided a large piece of the cell death puzzle, whilst simultaneously and firmly putting the gasdermin family into the limelight. In its purest form, GSDMD provides a connection between the innate alarm systems to an explosive, inflammatory form of cell death to jolt the local environment into immunological action. However, the gasdermin field has moved rapidly and significantly since the original seminal work and novel functions and mechanisms have been recently uncovered, particularly in response to infection. Gasdermins regulate and are regulated by mechanisms such as autophagy, metabolism and NETosis in fighting pathogen and protecting host. Importantly, activators and interactors of the other gasdermins, not just GSDMD, have been recently elucidated and have opened new avenues for gasdermin-based discovery. Key to this is the development of potent and specific tool molecules, so far a challenge for the field. Here we will cover some of these recently discovered areas in relation to bacterial infection before providing an overview of the pharmacological landscape and the challenges associated with targeting gasdermins.
Clinical and immune-related factors associated with exacerbation in adults with well-controlled generalized myasthenia gravis
Authors: Bi Zhuajin , Zhan Jiayang , Zhang Qing , Gao Huajie , Yang Mengge , Ge Huizhen , Gui Mengcui , Lin Jing , Bu Bitao
Published: May 2023

Objectives

To describe the clinical predictors and immune-related factors for exacerbation in adults with well-controlled generalized myasthenia gravis (GMG).

Methods

We conducted a retrospective analysis of 585 adults with well-controlled GMG from our institution to explore the risk factors for exacerbation. Furthermore, propensity score matching (PSM) was used to compare the proportions of lymphocyte subsets, and the levels of immunoglobulin, complement, and anti-acetylcholine receptor antibody (AChR-ab) in the peripheral blood of 111 patients with exacerbations and 72 patients without exacerbations.

Results

A total of 404 patients (69.1%) experienced at least one exacerbation, and the median (interquartile range) time to the first exacerbation was 1.5 years (0.8–3.1 years). Multivariable Cox regression analysis showed that age at onset, disease duration before enrollment, Myasthenia Gravis Foundation of America classification (MGFA) class III vs. class II, MGFA class IV-V vs. class II, AChR-ab levels, anti-muscle specific kinase antibody levels, thymus hyperplasia, prednisone plus immunosuppressants vs. prednisone treatment, and thymectomy were independent predictors for exacerbations [hazard ratio (HR) = 1.011, 1.031, 1.580, 1.429, 2.007, 2.033, 1.461, 0.798, and 0.651, respectively]. Propensity-matched analysis compared 51 patient pairs. After PSM, the peripheral blood proportions of CD3–CD19+ B cells, ratios of CD3+CD4+/CD3+CD8+ T cells, and AChR-ab levels were significantly increased, and the peripheral blood proportions of CD3+CD8+ T and CD4+CD25+CD127low+ regulatory T cells (Tregs) were significantly lower in patients with exacerbation than in those without exacerbation (all p < 0.05).

Conclusion

Myasthenia gravis (MG) exacerbations were more frequent in those patients with older onset age, longer disease duration, more severe MGFA classification, positive AChR-ab, and lack of combined immunotherapy or thymectomy treatment. On the other hand, CD3–CD19+ B cells, CD3+CD8+ T cells, Tregs, and AChR-ab in peripheral blood may be involved in the course of GMG exacerbation.
Bioinformatics and Raman spectroscopy-based identification of key pathways and genes enabling differentiation between acute myeloid leukemia and T cell acute lymphoblastic leukemia
Authors: Liang Haoyue , Kong Xiaodong , Cao Zhijie , Wang Haoyu , Liu Ertao , Sun Fanfan , Qi Jianwei , Zhang Qiang , Zhou Yuan
Published: May 2023

Acute myeloid leukemia (AML) and T cell acute lymphoblastic leukemia (T-ALL) are two of the most prevalent hematological malignancies diagnosed among adult leukemia patients, with both being difficult to treat and associated with high rates of recurrence and mortality. In the present study, bioinformatics approaches were used to analyze both of these types of leukemia in an effort to identify characteristic gene expression patterns that were subsequently validated via Raman spectroscopy. For these analyses, four Gene Expression Omnibus datasets (GSE13204, GSE51082, GSE89565, and GSE131184) pertaining to acute leukemia were downloaded, and differentially expressed genes (DEGs) were then identified through comparisons of AML and T-ALL patient samples using the R Bioconductor package. Shared DEGs were then subjected to Gene Ontology (GO) enrichment analyses and were used to establish a protein-protein interaction (PPI) network analysis. In total, 43 and 129 upregulated and downregulated DEGs were respectively identified. Enrichment analyses indicated that these DEGs were closely tied to immune function, collagen synthesis and decomposition, inflammation, the synthesis and decomposition of lipopolysaccharide, and antigen presentation. PPI network module clustering analyses further led to the identification of the top 10 significantly upregulated and downregulated genes associated with disease incidence. These key genes were then validated in patient samples via Raman spectroscopy, ultimately confirming the value of these genes as tools that may aid the differential diagnosis and treatment of AML and T-ALL. Overall, these results thus highlight a range of novel pathways and genes that are linked to the incidence and progression of AML and T-ALL, providing a list of important diagnostic and prognostic molecular markers that have the potential to aid in the clinical diagnosis and treatment of these devastating malignancies.
A participatory climate vulnerability assessment for recreational tidal flats fisheries in Belize and The Bahamas
Authors: Carroll Gemma , Eurich Jacob G. , Sherman Krista D. , Glazer Robert , Braynen Michael T. , Callwood Karlisa A. , Castañeda Adriel , Dahlgren Craig , Karr Kendra A. , Kleisner Kristin M. , Burns-Perez Virginia , Poon Sarah E. , Requena Nicanor , Sho Victor , Tate Shervin N. , Haukebo Sepp
Published: May 2023

Recreational fishing is a pillar of the multibillion-dollar tourism sector in the Caribbean, supporting economic development and community livelihoods. However, as climate change drives increased habitat degradation, key recreational target species may experience declines. To effectively prioritize adaptation and mitigation efforts it is critical to project climate change impacts on recreational species and the communities that depend on them. We conducted a comprehensive climate vulnerability assessment (CVA) for three recreationally important tidal flats species in Belize and The Bahamas: bonefish (Albula vulpes), tarpon (Megalops atlanticus), and permit (Trachinotus falcatus). Species vulnerability was assessed by coupling 1) a research-based CVA to evaluate the sensitivity and exposure of species to climate impacts with 2) a participatory workshop involving 17 fishing guides, resource managers, and science and policy experts working in fisheries systems in Belize and/or The Bahamas. The workshop elicited local expert knowledge to resolve and contextualize CVA scoring and to identify strategies to increase climate resilience. According to the research-based CVA, key climate factors in the Caribbean are expected to see a ‘very high’ magnitude of change by 2050. All three species exhibit ‘very high’ vulnerability to these changes based on life history traits and reliance on nearshore habitats that are exposed to rapid temperature increases and storm damage. The expert stakeholder group confirmed a ‘very high’ magnitude of expected climate impacts in the Caribbean region, to which bonefish, the most valuable species, is likely to have a ‘very high’ vulnerability. However, stakeholders perceived tarpon and permit to be less vulnerable to these impacts than the CVA predicted, based on “on the water” observations of their habitat flexibility and resilience to disturbance. The group identified strategies at the individual, community, national, and international levels to enhance climate resilience in the recreational fishing sector. Our work highlights how participatory CVA processes can support a stronger understanding of species’ vulnerability while building capacity and collaboration to increase climate change readiness.
Sandy shoreline recovery ability after breakwater removal
Authors: Chi Shanhang , Zhang Chi , Zheng Jinhai
Published: May 2023

The removal of coastal structures has emerged as an increasingly considered alternative nature-based solution to sandy coastal erosion due to unsuited structure construction. However, its effectiveness remains uncertain because the ability of natural beach recovery is unclear due to little understanding of shoreline response to the structure removal. In this study, we use a recently developed numerical model to explore the sandy shoreline recovery ability after the removal of an attached breakwater. Both recovery duration and recovery ratio are analyzed concerning various breakwater configurations and environmental settings in a simplified and generalized framework. We find that the sandy shoreline has the ability to naturally recover after breakwater removal but with different recovery durations (years to centuries) and recovery ratios (full to partial). A higher shoreline recovery ability (i.e., shorter duration and larger ratio) is related to shorter effective breakwater length, downdrift inclined breakwater direction, lower angle of wave incidence, and greater longshore sediment transport rate. We reveal that the behavior of sand spit evolution, including the extension and split of the sand spit, is the dominant mechanism for distinct shoreline recovery processes. Two simple formulas are finally proposed to preliminarily estimate shoreline recovery ability for practical purposes. The results of the present study provide new insights into coastal morphological resilience to engineering interventions.
What’s the key for success? Translocation, growth and thermal stress mitigation in the Mediterranean coral Cladocora caespitosa (Linnaeus, 1767)
Authors: Roveta Camilla , Coppari Martina , Calcinai Barbara , Di Camillo Cristina Gioia , Marrocco Teo , Pulido Mantas Torcuato , Puce Stefania , Torsani Fabrizio , Valisano Laura , Cerrano Carlo
Published: May 2023

Marine heat waves (MHWs) are affecting corals populations, advocating their inclusion in restoration actions since conservation measures may be not sufficient. Cladocora caespitosa is a Mediterranean reef-building, long-living species, with low recruitment rate and high juvenile mortality, leading to the need for its inclusion in international and European legislations. The aim of this study, conducted in the southern Tyrrhenian Sea, was to test the translocation of several C. caespitosa colonies thriving on an artificial substrate intended for demolition, applying transplantation techniques. Thirty-four colonies were transplanted in May 2018, and monitored over 4 years, to check for their persistence and health status. The shaded position of the recipient site resulted adequate, considering that colony survival rates were as high as 82.4%, 70.6% and 55.9% in October 2018, January 2020 and October 2022, respectively. Colonies presented signs of suffering only after the high temperatures occurred during summer 2022, with a decreasing rate of -2.5 ± 0.4 corallite/month. To better interpret the documented survival rates, 40 fragments of C. caespitosa were reared in aquaria to test temperature and light effects on growth rates and resistance to thermal stress, simulating a MHW and exacerbating the dim-light natural conditions of the recipient site, exposing half of the fragments to complete darkness. Only bigger fragments produced new corallites, with a rate of 1.3 ± 0.3 corallites/month, like the natural growth rate obtained in the field before the thermal anomaly, highlighting the suitability of ex-situ rearing as a potential tool to supply restoration project. After 5-days at 28.5°C, all fragments survived, despite showing tissue retraction, shorter tentacles, lower responsiveness, and zooxanthellae density variation. Overall, our results highlighted a promising plasticity of C. caespitosa in the field, representing a good candidate for restoration purposes. In aquaria this adaptive potential has been tested on a single genotype and more tests are needed to assess the intraspecific variability of these responses. A first insight into the species-based siting selection was provided to ensure the success of a restoration action. Our results point out the importance of knowing life history traits and ecological optima to design proper management and restoration measures.
Associations between intimate partner violence and adverse birth outcomes during pregnancy: a systematic review and meta-analysis
Authors: Guo Cancan , Wan Mengtong , Wang Yue , Wang Peijie , Tousey-Pfarrer Marissa , Liu Haoyang , Yu Liangming , Jian Lingqi , Zhang Mengting , Yang Ziqi , Ge Fenfen , Zhang Jun
Published: May 2023

Background

Intimate partner violence (IPV) has been associated with an elevated risk of multiple adverse birth outcomes, yet little is known about how specific IPV influences adverse birth outcomes. The aim of this study was to examine the association between IPV during pregnancy and adverse birth outcomes (i.e., preterm birth, low birth weight, and stillbirth).

Methods

Systematic searches were conducted using four databases: EMBASE, Web of Science, PubMed, and CINAHL for observational studies published from 1 January 2011 to 31 August 2021. Two reviewers independently carried out the literature search, study selection, data extraction, assessment of the study, and risk of bias assessment; disagreements were resolved by a third reviewer. A random-effect model was used to calculate the odds ratio (OR) with a 95% confidence interval (CI) for preterm birth, low birth weight, and stillbirth. I2 statistic accompanied by chi-square p-value was used to assess heterogeneity, and funnel plot and Peter's test were used to assess publication bias.

Results

In total, 23 studies met the inclusion criterion. IPV was associated with preterm birth (OR = 1.84; 95% CI: 1.37–2.49; I2 = 88%), low birth weight (OR = 2.73; 95% CI: 1.66–4.48; I2 = 95%), and stillbirth (OR = 1.74; 95% CI: 0.86–3.54; I2 = 64%). We attained comparable results among all specific IPV including physical, sexual, emotional, and mixed.

Conclusion

Intimate partner violence and specific IPV during pregnancy were significantly associated with adverse birth outcomes, especially for physical IPV. An urgent need for greater action to prevent or intervene in IPV during pregnancy is warranted.

Systematic review registration

CRD42021282936, https://www.crd.york.ac.uk/prospero/.
First successful treatment of Clostridium perfringens-associated emphysematous hepatitis: a case report
Authors: Bayerl Christian , Berg Ann-Kathrin , Angermair Stefan , Kim Damon , Hamm Bernd , Beyer Katharina , Schineis Christian
Published: May 2023

Emphysematous diseases of the abdomen are rare with an often inconspicuous presentation of symptoms and rapid lethal outcome if untreated. We report the first successfully treated case of Clostridium perfringens-associated emphysematous hepatitis. In the emergency room, a 79-year-old man presented with shortness of breath and deteriorated general condition since the morning of admission. Initial CT scans showed a small but rapidly expanding gas collection in liver segment 6. Emergency surgery with atypical liver resection was performed immediately. With early resection and prolonged administration of antibiotics in the presence of sepsis, the patient recovered successfully and was discharged 37 days after admission. As in our case, prompt diagnosis with early surgical treatment is crucial for the management of emphysematous hepatitis.
Developing a nomogram-based scoring model to estimate the risk of pulmonary embolism in respiratory department patients suspected of pulmonary embolisms
Authors: Lanfang Feng , Xu Ma , Jun Chen , Jia Zhao , Wenchen Li , Xinghua Jia
Published: May 2023

Objective

Pulmonary embolisms (PE) are clinically challenging because of their high morbidity and mortality. This study aimed to create a nomogram to accurately predict the risk of PE in respiratory department patients in order to enhance their medical treatment and management.

Methods

This study utilized a retrospective method to collect information on medical history, complications, specific clinical characteristics, and laboratory biomarker results of suspected PE patients who were admitted to the respiratory department at Affiliated Dongyang Hospital of Wenzhou Medical University between January 2012 and December 2021. This study involved a total of 3,511 patients who were randomly divided into a training group (six parts) and a validation group (four parts) based on a 6:4 ratio. The LASSO regression and multivariate logistic regression were used to develop a scoring model using a nomogram. The performance of the model was evaluated using receiver operating characteristic curve (AUC), calibration curve, and clinical decision curve.

Results

Our research included more than 50 features from 3,511 patients. The nomogram-based scoring model was established using six predictive features including age, smoke, temperature, systolic pressure, D-dimer, and fibrinogen, which achieved AUC values of 0.746 in the training cohort (95% CI 0.720–0.765) and 0.724 in the validation cohort (95% CI 0.695–0.753). The results of the calibration curve revealed a strong consistency between probability predicted by the nomogram and actual probability. The decision curve analysis (DCA) also demonstrated that the nomogram-based scoring model produced a favorable net clinical benefit.

Conclusion

In this study, we successfully developed a novel numerical model that can predict the risk of PE in respiratory department patients suspected of PE, which can not only appropriately select PE prevention strategies but also decrease unnecessary computed tomographic pulmonary angiography (CTPA) scans and their adverse effects.
Emergence of Aeromonas veronii strain co-harboring blaKPC–2, mcr-3.17, and tmexC3.2-tmexD3.3-toprJ1b cluster from hospital sewage in China
Authors: Zhu Zhichen , Wu Shuhua , Zhu Jie , Wang Tao , Wen Yicheng , Yang Chengcheng , Lv Jinnan , Zhang Haifang , Chen Liang , Du Hong
Published: May 2023

Introduction

The raise of multi-drug resistant bacteria involving carbapenem, colistin, or tigecycline resistance constitutes a threat to public health, which partly results from the transmission of corresponding mobile resistance genes, such as blaKPC and blaNDM for carbapenem, mcr for colistin, and tmexCD-toprJ gene cluster for tigecycline. Herein, we described the emergence of an Aeromonas veronii strain HD6454 co-harboring blaKPC–2, mcr-3.17, and tmexC3.2-tmexD3.3-toprJ1b gene cluster from hospital sewage.

Methods

Whole genome sequencing (WGS) was used to determine the genome sequence of HD6454, and the detailed genomic analysis of genetic elements or regions carrying key antimicrobial resistance genes (ARGs) from HD6454 were performed. Cloning experiment was conducted to confirm the function of key ARGs in mediating antimicrobial resistance. Conjugation experiment was conducted to determine the mobility of the plasmid.

Results

The results showed that this strain belonged to a novel sequence type (ST) variant ST1016, and carried 18 important ARGs. Among them, the blaKPC–2 was carried by non-self-transmissible IncP-6 plasmid, while tmexC3.2-tmexD3.3-toprJ1b gene cluster and mcr-3.17 were carried by integrative and mobilizable element (IME) or IME-related region in chromosome. The mcr-3.17, mcr-3.6, and mcr-3-like3 genes were further inferred to originate from IMEs of Aeromonas species. Additionally, for the first time, the mcr-3.17 was confirmed to confer low-level resistance to colistin under inducible expression, while tmexC3.2-tmexD3.3-toprJ1b gene cluster was confirmed to confer low-level resistance to tigecycline.

Discussion

This is the first report of a strain co-harboring blaKPC–2, mcr-3.17, and tmexC3.2-tmexD3.3-toprJ1b gene cluster. Although the resistance and/or mobility of these ARGs are limited in this strain, the emergence of this multiple important ARGs-carrying strain deserves further attention.
Enabling deep-space experimentations on cyanobacteria by monitoring cell division resumption in dried Chroococcidiopsis sp. 029 with accumulated DNA damage
Authors: Fagliarone Claudia , Mosca Claudia , Di Stefano Giorgia , Leuko Stefan , Moeller Ralf , Rabbow Elke , Rettberg Petra , Billi Daniela
Published: May 2023

Cyanobacteria are gaining considerable interest as a method of supporting the long-term presence of humans on the Moon and settlements on Mars due to their ability to produce oxygen and their potential as bio-factories for space biotechnology/synthetic biology and other applications. Since many unknowns remain in our knowledge to bridge the gap and move cyanobacterial bioprocesses from Earth to space, we investigated cell division resumption on the rehydration of dried Chroococcidiopsis sp. CCMEE 029 accumulated DNA damage while exposed to space vacuum, Mars-like conditions, and Fe-ion radiation. Upon rehydration, the monitoring of the ftsZ gene showed that cell division was arrested until DNA damage was repaired, which took 48 h under laboratory conditions. During the recovery, a progressive DNA repair lasting 48 h of rehydration was revealed by PCR-stop assay. This was followed by overexpression of the ftsZ gene, ranging from 7.5- to 9-fold compared to the non-hydrated samples. Knowing the time required for DNA repair and cell division resumption is mandatory for deep-space experiments that are designed to unravel the effects of reduced/microgravity on this process. It is also necessary to meet mission requirements for dried-sample implementation and real-time monitoring upon recovery. Future experiments as part of the lunar exploration mission Artemis and the lunar gateway station will undoubtedly help to move cyanobacterial bioprocesses beyond low Earth orbit. From an astrobiological perspective, these experiments will further our understanding of microbial responses to deep-space conditions.
Characteristics of endophytic bacteria and active ingredients in the Eucommiae cortex from different origins
Authors: Liang Xuejuan , Zhou Kang , Li Penghui , Wan Dan , Liu Jing , Yi Xin , Peng Yanmei
Published: May 2023

Objective

This study aimed to explore the differences between Eucommiae cortex (EC) endophytic bacteria from different origins and their effects on the active ingredients of EC.

Methods

A total of 10 samples of Eucommia ulmoides Oliv. (E. ulmoides) bark were collected from each of the following four regions, namely, Zunyi in Guizhou (GZ), Baokang in Hubei (HUB), Cili in Hunan (HUN), and Loyang in Shaanxi (SX). Subsequently, the contents of the main active ingredients of EC were determined by ultra-performance liquid chromatography (UPLC), and the endophytic bacteria of EC were detected by 16S rRNA sequencing. The relationship between the dominant endophytic bacteria and the active ingredients was investigated by correlation analysis.

Results

A total of 4,551 different operational taxonomic units (OTUs) were delineated in the four groups of samples, of which 585, 439, 957, and 684 genera were annotated from GZ, HUB, HUN, and SX, respectively. The richness and diversity of endophytic bacteria from different origins were ranked as HUN > SX > GZ or HUB. The analysis demonstrated that there was no significant correlation between the diversity and richness of endophytic bacteria in EC and its active ingredients. Nevertheless, notable variations in the community structures of endophytic bacteria were observed across different origins, and they had a considerable impact on certain active ingredients in EC. Comamonas and Cedecea were the dominant genera. Characteristic bacteria of different origins could be clearly distinguished. Simultaneous, significant correlations had been identified between some characteristic endophytic bacteria derived from different origins and active ingredients of EC. For example, Delftia, a characteristic bacterium from GZ, showed a significant positive correlation with pinoresinol diglucoside. Paenibacillus and Klebsiella, two characteristic bacteria from HUB, exhibited significant positive correlations with geniposidic acid. Thauera, a characteristic bacterium from HUN, demonstrated a significant positive correlation with geniposide. Brevundimonas, a characteristic bacterium from SX, displayed a significant positive correlation with pinoresinol diglucoside.

Conclusion

There was a complex correlation between EC endophytic bacteria and active ingredient content, while EC endophytic bacteria from different origins had significant differences at the genus level.
Culturable bacterial endophytes of Aconitum carmichaelii Debx. were diverse in phylogeny, plant growth promotion, and antifungal potential
Authors: Zou Lan , Wang Qian , Li Muyi , Wang Siyu , Ye Kunhao , Dai Wei , Huang Jing
Published: May 2023

Medicinal plants harbor tremendously diverse bacterial endophytes that maintain plant growth and health. In the present study, a total of 124 culturable bacterial endophytes were isolated from healthy Aconitum carmichaelii Debx. plants. These strains were clustered into 10 genera based on full-length 16S rDNA sequences, among which Bacillus and Pseudomonas were the dominant genera. In addition, A. carmichaelii may capture 10 potential new bacterial species based on multi-locus sequence analysis of three housekeeping genes (gyrA, rpoB, and atpD). The majority of these bacterial endophytes exhibited plant growth-promoting ability through diverse actions including the production of either indole acetic acid and siderophore or hydrolytic enzymes (glucanase, cellulose, and protease) and solubilization of phosphate or potassium. A total of 20 strains inhibited hyphal growth of fungal pathogens Sclerotium rolfsii and Fusarium oxysporum in vitro on root slices of A. carmichaelii by the dual-culture method, among which Pseudomonas sp. SWUSTb-19 showed the best antagonistic activity. Field experiment confirmed that Pseudomonas sp. SWUSTb-19 significantly reduced the occurrence of southern blight and promoted plant biomass compared with non-inoculation treatment. The possible mode of actions for Pseudomonas sp. SWUSTb-19 to antagonize against S. rolfsii involved the production of glucanase, siderophore, lipopeptides, and antimicrobial volatile compounds. Altogether, this study revealed that A. carmichaelii harbored diverse plant growth-promoting bacterial endophytes, and Pseudomonas sp. SWUSTb-19 could be served as a potential biocontrol agent against southern blight.
The carboxypeptidase B and carbonic anhydrase genes play a reproductive regulatory role during multiple matings in Ophraella communa
Authors: Chen Guangmei , Gao Xuyuan , Zhang Yan , Ma Chao , Ma Weihua , Zhou Zhongshi
Published: May 2023

Seminal fluid proteins (SFPs) are key factors in sexual reproduction and are transferred to females during mating with sperm. SFPs have a nutritional value because they protect and activate sperm storage and release to optimize fecundity. Multiple matings promote ovipositioning in several insect species. Therefore, insects may obtain more SFP through multiple matings to maximize reproduction, but this process has not yet been clearly confirmed. Here, the relationship between multiple matings and the SFPs in Ophraella communa (Coleoptera: Chrysomelidae), a biological control agent of the common ragweed Ambrosia artemisiifolia (Asterales: Asteraceae), was studied. Multiple matings significantly increased female fecundity and ovary egg deposition. Carboxypeptidase B (OcCpb) and carbonic anhydrase (OcCa) genes were identified as putative SFP genes in O. communa and they showed strong male-biased expression. Additionally, OcCpb and OcCa expression was upregulated in the bursa copulatrix of mating females compared to that in virgin females, but their expression gradually declined after copulation. Furthermore, OcCpb and OcCa knockdown in males led to a decrease in insect fecundity compared to that in the control. The reproductive tract of females mated with dsRNA-treated males was dissected and observed and, notably, the ovaries produced significantly fewer eggs. These data suggest that OcCpb and OcCa play regulatory roles during multiple matings in O. communa.
The human neurosecretome: extracellular vesicles and particles (EVPs) of the brain for intercellular communication, therapy, and liquid-biopsy applications
Authors: Soleymani Taliah , Chen Tzu-Yi , Gonzalez-Kozlova Edgar , Dogra Navneet
Published: May 2023

Emerging evidence suggests that brain derived extracellular vesicles (EVs) and particles (EPs) can cross blood-brain barrier and mediate communication among neurons, astrocytes, microglial, and other cells of the central nervous system (CNS). Yet, a complete understanding of the molecular landscape and function of circulating EVs & EPs (EVPs) remain a major gap in knowledge. This is mainly due to the lack of technologies to isolate and separate all EVPs of heterogeneous dimensions and low buoyant density. In this review, we aim to provide a comprehensive understanding of the neurosecretome, including the extracellular vesicles that carry the molecular signature of the brain in both its microenvironment and the systemic circulation. We discuss the biogenesis of EVPs, their function, cell-to-cell communication, past and emerging isolation technologies, therapeutics, and liquid-biopsy applications. It is important to highlight that the landscape of EVPs is in a constant state of evolution; hence, we not only discuss the past literature and current landscape of the EVPs, but we also speculate as to how novel EVPs may contribute to the etiology of addiction, depression, psychiatric, neurodegenerative diseases, and aid in the real time monitoring of the “living brain”. Overall, the neurosecretome is a concept we introduce here to embody the compendium of circulating particles of the brain for their function and disease pathogenesis. Finally, for the purpose of inclusion of all extracellular particles, we have used the term EVPs as defined by the International Society of Extracellular Vesicles (ISEV).
External ureteric stent versus internal double J stent in kidney transplantation: a retrospective analysis on the incidence of urological complications and urinary tract infections
Authors: Hazenberg Ietje T. , Middelkoop Stephanie J. M. , de Joode Anoek A. E. , Rabbeljee Juliette D. , Pol Robert A. , Doornweerd Benjamin H. J. , Sanders Jan-Stephan F. , Stegeman Coen A.
Published: May 2023

Introduction

Urologic complications (UCs) and urinary tract infections (UTIs) are common after kidney transplantation. Intraoperative stent placement at the vesicoureteric anastomosis reduces UC risk, but increases UTI risk.

Methods

In 2014 our stenting protocol changed from external ureteric stent (ES) to internal double J stent (DJ). We retrospectively studied the occurrence of UCs and UTIs in relation to ES or DJ in 697 kidney recipients.

Methods

An ES was used in 403 patients (57.8%), in 294 (42.2%) a DJ. ES was removed 7-12 days and DJ 3-4 weeks post-operative. Induction immunosuppression was the same in both groups. Primary outcomes at 6 months follow-up were UC (urinary leakage/ureter stenosis) and UTI; they were related to stenting procedure and clinical and transplant characteristics. The incidence of UCs was similar for ES (8.4%) and DJ (6.8%), p=0.389. ES use was a significant risk factor for UTI (OR 1.69 (1.15-2.50), p=0.008). Post-transplant hospitalization was significantly shorter in the DJ group. Despite more acute rejection episodes with ES (ES/DJ: 16.4%/6.1%, p<0.001), no clinical relevant differences in graft outcomes existed.

Discussion

A DJ is, compared to ES, associated with a lower incidence of UTIs and comparable occurrence of UCs and is therefore the preferred technique for stenting the vesicoureteric anastomosis.
Alterations of brain gray matter volume in children with obstructive sleep apnea
Authors: Yu Chenyi , Fu Yuchuan , Lu Yi , Huang Yinyin , Chen Fangfang , Wei Jiayun , Li Lingling , Ampadu Janet Akoto , Wang Yu , Zheng Weikun , Jiang Changcan , Li Weiyuan , Lui Su , Cai Xiaohong
Published: May 2023

Objective

Obstructive sleep apnea (OSA) seriously affects the children's cognitive functions, but the neuroimaging mechanism of cognitive impairment is still unclear. The purpose of our study was to explore the difference in brain local gray matter volume (GMV) between children with OSA and non-OSA, and the correlation between the difference regions of brain gray matter volume and cognitive, the severity of OSA.

Method

Eighty-three children aged 8–13 years were recruited in our study, 52 children were diagnosed as OSA by polysomnography, and 31 as the non-OSA. All the subjects were underwent high-resolution 3-dimensional T1-weighted magnetic resonance images. The voxel-based morphometry (VBM) was be used to analyse the local GMV. The Das-Naglieri cognitive assessment system (DN: CAS) was used to assess the subjects' cognitive. The difference of local GMV between the two groups was analyzed by two-sample T-test. The PSG variables and the scores of DN: CAS between the OSA group and non-OSA group were compared by independent samples t-tests. Pearson correlation was used to calculate the association between the difference areas of gray matter volumes in brain and DN: CAS scores, obstructive apnea/hypopnea index (OAHI, an index of the severity of OSA).

Results

The gray matter volume of the right Middle Frontal Gyrus (MFG_R) in OSA children were larger than the non-OSA children, and the OSA children had lower scores of the Word Series in DN: CAS. There was negative correlation between the scores of Expressive Attention in DN: CAS and the gray matter volume of the right middle frontal gyrus, and it was no significantly correlation between OAHI and the gray matter volume of the right middle frontal gyrus.

Conclusion

Our results suggest that the development of gray matter volume in frontal cortex, which associated with attention, were sensitive to the effects of OSA, provides neuroimaging evidence for cognitive impairment in children with OSA.
Transcriptomic analysis reveals the potential biological mechanism of AIS and lung adenocarcinoma
Authors: Qin Rong-Xing , Yang Yue , Chen Jia-Feng , Huang Li-Juan , Xu Wei , Qin Qing-Chun , Liang Xiao-Jun , Lai Xin-Yu , Huang Xiao-Ying , Xie Min-Shan , Chen Li
Published: May 2023

Introduction

Acute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD.

Methods

Transcriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines.

Results

We identified the molecular mechanisms underlying hub genes in AIS and LUAD and found thatCCNA2, CCNB1, CDKN2A, andCDK1were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling.

Discussion

Our findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.