bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete genome assembly and methylome dissection of Methanococcus aeolicus PL15/Hp
Authors: Fomenkov Alexey , Weigele Peter , McClung Colleen , Madinger Casey , Roberts Richard J.
Published: April 2023

Although restriction-modification systems are found in both Eubacterial and Archaeal kingdoms, comparatively less is known about patterns of DNA methylation and genome defense systems in archaea. Here we report the complete closed genome sequence and methylome analysis of Methanococcus aeolicus PL15/Hp, a strain of the CO2-reducing methanogenic archaeon and a commercial source for MaeI, MaeII, and MaeIII restriction endonucleases. The M. aeolicus PL15/Hp genome consists of a 1.68 megabase circular chromosome predicted to contain 1,615 protein coding genes and 38 tRNAs. A combination of methylome sequencing, homology-based genome annotation, and recombinant gene expression identified five restriction-modification systems encoded by this organism, including the methyltransferase and site-specific endonuclease of MaeIII. The MaeIII restriction endonuclease was recombinantly expressed, purified and shown to have site-specific DNA cleavage activity in vitro.
Alteration of pro-carcinogenic gut microbiota is associated with clear cell renal cell carcinoma tumorigenesis
Authors: Yang Bo-Yu , Zhao Fang-Zhou , Li Xuan-Hao , Zhao Mei-Shan , Lv Jing-Cheng , Shi Ming-Jun , Li Jun , Zhou Zhi-Yuan , Wang Jing-Jing , Song Jian
Published: April 2023

Objective

Increasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC.

Methods

In a pilot case-control study among 30 ccRCC patients (RCC group) and 30 healthy controls (Control group), 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on the TCGA database.

Results

Alpha diversity found there were no significant microbial diversity differences of gut microbiota between the RCC group and the Control group. However, beta diversity analysis showed that the overall structures of the two groups were significantly separated (p = 0.008). Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which nine species were enriched in the RCC group such as Desulfovibrionaceae, and 11 species were less abundant such as four kinds of Lactobacillus. Concomitantly, serum level of taurine, which was considered to be consumed by Desulfovibrionaceae and released by Lactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such as Gabbr1 was upregulated in ccRCC patients.

Conclusion

Reduction of protective bacteria, proliferation of sulfide-degrading bacteria Desulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.
Application of a novel lytic Jerseyvirus phage LPSent1 for the biological control of the multidrug-resistant Salmonella Enteritidis in foods
Authors: Al-Hindi Rashad R. , Alharbi Mona G. , Alotibi Ibrahim , Azhari Sheren A. , Algothmi Khloud M. , Esmael Ahmed
Published: April 2023

Non-typhoidalSalmonellais the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistantSalmonellastrains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producerSalmonella entericaserovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including milk, water, apple juice, and chicken breasts. One lytic phage (LPSent1) was selected based on its robust and stable lytic activity. Phage LPSent1 belonged to the genusJerseyviruswithin theJerseyvirinaesubfamily. The lysis time of phage LPSent1 was 60 min with a latent period of 30 min and each infected cell burst about 112 plaque-forming units. Phage LPSent1 showed a narrow host range. Furthermore, the LPSent1 genome did not encode any virulence or lysogenic genes. In addition, phage LPSent1 had wide pH tolerance, prolonged thermal stability, and was stable in food articles lacking its susceptible host for 48 h.In vitroapplications of phage LPSent1 inhibited free planktonic cells and biofilms ofSalmonellaEnteritidis EG.SmE1 with a lower occurrence to form phage-resistant bacterial mutants which suggests promising applications on food articles. Application of phage LPSent1 at multiplicities of infections of 100 or 1000 showed significant inhibition in the bacterial count ofSalmonellaEnteritidis EG.SmE1 by 5 log10/sample in milk, water, apple juice, and chicken breasts at either 4°C or 25°C. Accordingly, taken together these findings establish phage LPSent1 as an effective, promising candidate for the biocontrol of MDRSalmonellaEnteritidis in ready-to-eat food.
In vitro cell culture models to study hepatitis B and D virus infection
Authors: Guo Hongbo , Urban Stephan , Wang Wenshi
Published: April 2023

Chronic infection with the hepatitis B virus (HBV) and hepatitis D virus (HDV) can cause a major global health burden. Current medication regimens can repress viral replication and help to control disease progression, but a complete cure is hardly achieved due to the difficulties to eradicate viral templates (cccDNA and integrates). To develop novel curative antiviral therapies for HBV/HDV infection, it is vital to precisely understand the details of the molecular biology of both viruses and the virus-host interactions. One important prerequisite for gaining this aim is the availability of suitable in vitro models that support HBV/HDV infection, replicate both viruses via their authentic template and allow to adequately study host cell responses. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) receptor as the most crucial host factor promoted HBV/HDV research to a new era. Recently, the structure of human NTCP was solved, gaining a deeper understanding of HBV recognition as the bona fide receptor. After decades of continuous efforts, new progress has been achieved in the development of cell culture models supporting HBV/HDV study. This review summarizes the cell culture models currently available, discusses the advantages and disadvantages of each model, and highlights their future applications in HBV and HDV research.
Integration of microRNA and mRNA analyses depicts the potential roles of Momordica charantia saponin administration in insulin resistance of juvenile common carp (Cyprinus carpio) fed with a high-starch diet
Authors: Fan Ze , Wang Liansheng , Li Chenhui , Wu Di , Li Jinnan , Zhang Haitao , Xiong Siwei , Miao Linghong , Ge Xianping , Li Zhengwei
Published: April 2023

Background: The regulation of target gene mRNA mediated by microRNA may play an important role in glucose metabolism in fish. Previous research findings of our research group revealed that Momordica charantia saponin (MS) administration in a high-starch diet could improve insulin resistance of common carp through renovating insulin signaling pathways, whose fundamental mechanisms have remained unknown by far. To reveal this potential mechanism, we aimed to investigate the difference in miRNA and mRNA expression profiles between common carp fed with high-starch diets containing MS (HS_MS1 and HS_MS2) and common carp fed with high-starch (HS) diets.

Results: Through miRNA deep-sequencing, 10 significantly differentially expressed miRNAs in HC and HS_MS1, including one upregulated and nine downregulated miRNAs, were identified, whereas 10 significantly differentially expressed miRNAs in HC and HS_MS2, including four upregulated and six downregulated miRNAs, were identified. These miRNAs may not only be involved in the regulation of insulin signaling pathways and insulin resistance in common carp but also be the markers for liver insulin resistance in MS therapy for the remission of insulin resistance. This study identified 10 potential known miRNAs, namely, ccr-miR-10b, ccr-miR-122, ccr-miR-143, ccr-miR-146a, ccr-miR-155, ccr-miR-16c, ccr-miR-200a, ccr-miR-29a, ccr-miR-34, and ccr-miR-375, as candidates participating in modulating the liver insulin resistance. According to the biopathway enrichment analysis of the 252 target genes using the KEGG classical biopathway database, the relative expression levels of gsk3bb, pik3r1, and pik3r3b were analyzed using RNA-seq. Compared to the HC group, a significant decrease in the relative expression levels of pik3r1 and pik3r3b was observed in HS_MS1 and HS_MS2 groups (p < 0.05). This study raised a presumption of the presence of ccr-miR-29a targeting pik3r1 or ccr-miR-143 targeting pik3r3 playing likely roles in Momordica charantia saponins remitting the liver insulin resistance.

Conclusion: The findings will further deepen the understanding of the carbohydrate metabolism of common carp and provide an important scientific basis for the application of Momordica saponins as functional nutrients to alleviate insulin resistance of fish in fish culture.
Molecular characterization of colorectal mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, identified by multiomic data analysis
Authors: Xu Kailun , Zheng Shu , Li Baosheng , Shao Yingkuan , Yin Xiaoyang
Published: April 2023

Adenocarcinoma not otherwise specified (AC) and mucinous adenocarcinoma (MC) have different biological behaviors and clinical features. We utilized our previous proteomic data and public transcriptome, single-cell transcriptome, and spatial transcriptome databases to profile the molecular atlas of the tumor microenvironments of MC, AC, and normal colon tissues. By exploring the general and specific molecular features of AC and MC, we found that AC was immune-active but exposed to a hypoxic microenvironment. MC cells could protect against DNA damage, and the microenvironment was unfavorable to leukocyte transendothelial migration. We identified several potential molecular and cellular targets of AC and MC for future research. We also highlighted that the major difference between AC and MC was not the variety of cell types and functions but possibly cell interactions. Stromal and epithelial cell interactions play important roles in both MC and AC, but different regulatory pathways were involved.
Comparative study of size exclusion chromatography for isolation of small extracellular vesicle from cell-conditioned media, plasma, urine, and saliva
Authors: Contreras Hector , Alarcón-Zapata Pedro , Nova-Lamperti Estefania , Ormazabal Valeska , Varas-Godoy Manuel , Salomon Carlos , Zuniga Felipe A.
Published: April 2023

Introduction: Extracellular vesicles (EVs) are secreted from all types of cells and are involved in the trafficking of proteins, metabolites, and genetic material from cell to cell. According to their biogenesis and physical properties, EVs are often classified as small EVs (including exosomes) or large EVs, and large oncosomes. A variety of methods are used for isolated EVs; however, they have several limitations, including vesicle deformation, reduced particle yield, and co-isolate protein contaminants. Here we present an optimized fast and low-cost methodology to isolate small EVs (30–150 nm) from biological fluids comparing two SEC stationary phases, G200/120 and G200/140 columns.

Methods: The optimization parameters considered were a) the selection of the stationary phase, b) the eluate volume per fraction, and c) the selection of the enriched 30–150 nm EVs-fractions. The efficiency and separation profile of each UF/SEC fraction was evaluated by Nanoparticle tracking analysis (NTA), flow cytometry, total protein quantification, and Western blot.

Results: Both columns can isolate predominantly small EVs with low protein contaminants from plasma, urine, saliva, and HEK293-derived EV from collection medium. Column G200/ 40 offers a more homogeneous enrichment of vesicles between 30 and 150 nm than G200/120 [76.1 ± 4.4% with an average size of 85.9 ± 3.6 nm (Mode: 72.8 nm)] in the EV collection medium. The enrichment, estimated as the vesicle-to-protein ratio, was 1.3 × 1010 particles/mg protein for G200/40, obtaining a more significant EVs enrichment compared to G200/120. The optimized method delivers 0.8 ml of an EVs-enriched-outcome, taking only 30 min per sample. Using plasma, the enrichment of small EVs from the optimized method was 70.5 ± 0.18%, with an average size of 119.4 ± 6.9 nm (Mode: 120.3 nm), and the enrichment of the vesicle isolation was 4.8 × 1011 particles/mg protein. The average size of urine and saliva -EVs samples was 147.5 ± 3.4 and 111.9 ± 2.5 nm, respectively. All the small EVs isolated from the samples exhibit the characteristic cup-shaped morphology observed by Transmission electron microscopy (TEM).

Discussion: This study suggests that the combination of methods is a robust, fast, and improved strategy for isolating small EVs.
Elevated red blood cell distribution width levels predict depression after intracerebral hemorrhage: A 3-month follow-up study
Authors: Zhou Xianping , Li Yaqiang , Sun Zhongbo , Mu Li , Ma Yaoyao
Published: April 2023

Objectives

Inflammation vitally impacts the progression of depression resulting from intracerebral hemorrhage (ICH), while red blood cell distribution width (RDW) marks inflammatory-related diseases. The present study aimed at evaluating how RDW affects depression after ICH.

Methods

From prospective analyses of patients admitted to our department between January 2017 and September 2022, ICH patients with complete medical records were evaluated. The 17-item Hamilton Depression (HAMD-17) scale was used for measuring the depressive symptoms at 3 months after ICH. Diagnosis of post-ICH depression was conducted for patients based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.

Results

A total of 438 patients were enrolled in the study, out of which 93 (21.23%) patients had PSD at the 3-month follow-up. Accordingly, patients with depression had higher RDW levels (13.70 [IQR: 13.56–13.89] vs.13.45 [IQR: 12.64–13.75], p < 0.001) at admission compared with those without depression. In multivariate analyses, RDW was used for independently predicting the depression after ICH at 3 months (OR: 2.832 [95% CI: 1.748–4.587], p < 0.001). After adjusting the underlying confounding factors, the odds ratio (OR) of depression after ICH was 4.225 (95% CI: 1.686–10.586, p = 0.002) for the highest tertile of RDW relative to the lowest tertile. With an AUC of 0.703 (95% CI: 0.649–0.757), RDW demonstrated a significantly better discriminatory ability relative to CRP and WBC. RDW as an indicator for predicting depression after ICH had an optimal cutoff value of 13.68, and the sensitivity and specificity were 63.4% and 64.6%, respectively.

Conclusions

Elevated RDW level predicted post-ICH depression at 3 months, confirming RDW as an effective inflammatory marker for predicting depression after ICH.
A nomogram for predicting the risk of pulmonary embolism in neurology department suspected PE patients: A 10-year retrospective analysis
Authors: Jianling Qiang , Lulu Jin , Liuyi Qiu , Lanfang Feng , Xu Ma , Wenchen Li , Maofeng Wang
Published: April 2023

Objective

The purpose of this retrospective study was to establish a numerical model for predicting the risk of pulmonary embolism (PE) in neurology department patients.

Methods

A total of 1,578 subjects with suspected PE at the neurology department from January 2012 to December 2021 were considered for enrollment in our retrospective study. The patients were randomly divided into the training cohort and the validation cohort in the ratio of 7:3. The least absolute shrinkage and selection operator regression were used to select the optimal predictive features. Multivariate logistic regression was used to establish the numerical model, and this model was visualized by a nomogram. The model performance was assessed and validated by discrimination, calibration, and clinical utility.

Results

Our predictive model indicated that eight variables, namely, age, pulse, systolic pressure, hemoglobin, neutrophil count, low-density lipoprotein, D-dimer, and partial pressure of oxygen, were associated with PE. The area under the receiver operating characteristic curve of the model was 0.750 [95% confidence interval (CI): 0.721–0.783] in the training cohort and 0.742 (95% CI: 0.689–0.787) in the validation cohort, indicating that the model showed a good differential performance. A good consistency between the prediction and the real observation was presented in the training and validation cohorts. The decision curve analysis in the training and validation cohorts showed that the numerical model had a good net clinical benefit.

Conclusion

We established a novel numerical model to predict the risk factors for PE in neurology department suspected PE patients. Our findings may help doctors to develop individualized treatment plans and PE prevention strategies.
Investigation of shared genes and regulatory mechanisms associated with coronavirus disease 2019 and ischemic stroke
Authors: Wu Hao , Han Fei
Published: April 2023

Objective

Clinical associations between coronavirus disease (COVID-19) and ischemic stroke (IS) have been reported. This study aimed to investigate the shared genes between COVID-19 and IS and explore their regulatory mechanisms.

Methods

Published datasets for COVID-19 and IS were downloaded. Common differentially expressed genes (DEGs) in the two diseases were identified, followed by protein–protein interaction (PPI) network analysis. Moreover, overlapping module genes associated with the two diseases were investigated using weighted correlation network analysis (WGCNA). Through intersection analysis of PPI cluster genes and overlapping module genes, hub-shared genes associated with the two diseases were obtained, followed by functional enrichment analysis and external dataset validation. Moreover, the upstream miRNAs and transcription factors (TFs) of the hub-shared genes were predicted.

Results

A total of 91 common DEGs were identified from the clusters of the PPI network, and 129 overlapping module genes were screened using WGCNA. Based on further intersection analysis, four hub-shared genes in IS and COVID-19 were identified, including PDE5A, ITGB3, CEACAM8, and BPI. These hub-shared genes were remarkably enriched in pathways such as ECM-receptor interaction and focal adhesion pathways. Moreover, ITGB3, PDE5A, and CEACAM8 were targeted by 53, 32, and 3 miRNAs, respectively, and these miRNAs were also enriched in the aforementioned pathways. Furthermore, TFs, such as lactoferrin, demonstrated a stronger predicted correlation with the hub-shared genes.

Conclusion

The four identified hub-shared genes may participate in crucial mechanisms underlying both COVID-19 and IS and may exhibit the potential to be biomarkers or therapeutic targets for the two diseases.
Layer-dependent stability of intracortical recordings and neuronal cell loss
Authors: Urdaneta Morgan E. , Kunigk Nicolas G. , Peñaloza-Aponte Jesus D. , Currlin Seth , Malone Ian G. , Fried Shelley I. , Otto Kevin J.
Published: April 2023

Intracortical recordings can be used to voluntarily control external devices via brain-machine interfaces (BMI). Multiple factors, including the foreign body response (FBR), limit the stability of these neural signals over time. Current clinically approved devices consist of multi-electrode arrays with a single electrode site at the tip of each shank, confining the recording interface to a single layer of the cortex. Advancements in manufacturing technology have led to the development of high-density electrodes that can record from multiple layers. However, the long-term stability of neural recordings and the extent of neuronal cell loss around the electrode across different cortical depths have yet to be explored. To answer these questions, we recorded neural signals from rats chronically implanted with a silicon-substrate microelectrode array spanning the layers of the cortex. Our results show the long-term stability of intracortical recordings varies across cortical depth, with electrode sites around L4-L5 having the highest stability. Using machine learning guided segmentation, our novel histological technique, DeepHisto, revealed that the extent of neuronal cell loss varies across cortical layers, with L2/3 and L4 electrodes having the largest area of neuronal cell loss. These findings suggest that interfacing depth plays a major role in the FBR and long-term performance of intracortical neuroprostheses.
The effect of omega-3 fatty acids on alcohol-induced damage
Authors: Serrano Maitane , Rico-Barrio Irantzu , Grandes Pedro
Published: April 2023

Alcohol is the most widely consumed psychoactive substance in the world that has a severe impact on many organs and bodily systems, particularly the liver and nervous system. Alcohol use during pregnancy roots long-lasting changes in the newborns and during adolescence has long-term detrimental effects especially on the brain. The brain contains docosahexaenoic acid (DHA), a major omega-3 (n-3) fatty acid (FA) that makes up cell membranes and influences membrane-associated protein function, cell signaling, gene expression and lipid production. N-3 is beneficial in several brain conditions like neurodegenerative diseases, ameliorating cognitive impairment, oxidative stress, neuronal death and inflammation. Because alcohol decreases the levels of n-3, it is timely to know whether n-3 supplementation positively modifies alcohol-induced injuries. The aim of this review is to summarize the state-of-the-art of the n-3 effects on certain conditions caused by alcohol intake, focusing primarily on brain damage and alcoholic liver disease.
Reconsidering the T category for the T3 non-small cell lung cancer with additional tumor nodules in the same lobe: A population-based study
Authors: Cai Jing-Sheng , Yang Fan , Wang Xun
Published: April 2023

Background

This study aimed to evaluate the prognosis of the T3 non-small cell lung cancer (NSCLC) patients with additional tumor nodules in the same lobe (T3-Add), and externally validate the current T category of this population.

Methods

NSCLC data deposited in the Surveillance, Epidemiology, and End Results (SEER) dataset was extracted. Survivals were estimated using the Kaplan-Meier method with a log-rank test. Propensity score matching (PSM) was performed to reduce bias. The least absolute shrinkage and selection operator (LASSO)-penalized Cox model was used to determine the prognostic factors.

Results

A total of 41,370 eligible cases were included. There were 2,312, 20,632, 12,787, 3,374 and 2,265 cases in the T3-Add, T1, T2, T3 and T4 group, respectively. The Kaplan-Meier curves demonstrated that the survivals of the T3-Add patients were superior to those of the T3 patients both before and after PSM. Additionally, the OS of the T3-Add patients were worse than that of the T2 patients, but the CSS differences between these two groups were not statistically significant. In the subset analyses, the survivals of the T3-Add patients were inferior to those of the T2a patients, but were comparable to those of the T2b patients (5-year OS rate: 54.3% vs. 57.2%, P = 0.884; 5-year CSS rate: 76.2% vs. 76.8%, P = 0.370). In the T3-Add & T2b matched pair, multivariable Cox analysis further confirmed that T category was not a prognostic factor for survivals.

Conclusion

T3-Add and T2b NSCLC patients had similar survivals, and we proposed that it is necessary to reconsider the T category of the patients with additional nodules in the same lobe in the forthcoming 9th edition of TNM staging manual.
Research trends and prospects on brain metastasis from breast cancer: A bibliometric analysis
Authors: Wu Si-qi , Liu Yan , Zhou Jie , You Yan-ting , Zhou Xing-hong , Chen Li-qian , Kwan Hiu Yee , Zhao Xiao-shan , Wu Yi-fen , Liu Yan-yan
Published: April 2023

Introduction

Brain metastasis is the terminal event of breast cancer with poor prognoses. Therefore, this article aimed to provide an updated summary on the development, hotspots, and research trends of brain metastasis from breast cancer based on bibliometric analysis.

Method

Publications on breast cancer with brain metastasis retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and other online bibliometric analysis platforms were used to analyze and visualize the result.

Result

In totality, 693 researchers from 3,623 institutions across 74 counties and regions published a total of 2,790 papers in 607 journals. There was a noticeable increase in publications in 2006. The United States was the dominant country with the most publications followed by China. University Texas MD Anderson Cancer Center was the most productive institution, while Dana Farber Cancer Institution was the most cited. Journal of Neuro-Oncology published the most papers, while Journal of Clinical Oncology ranked first based on cocited analysis. Nancy U. Lin was the most productive and cited author with high influence. There was a focus on basic research, clinical trials, local therapy, treatment optimization, and epidemiological studies regarding brain metastases from breast cancer. References focused on pathogenesis, prevention, treatment, and prognosis were cited most frequently, among which the clinical trial of novel treatment attracted most attention from researchers. Reference citation burst detection suggested that new therapies such as the novel tyrosine kinase inhibitor and antibody–drug conjugate may lead the research trends in the future.

Conclusion

High-income countries contributed more to the field of breast cancer with brain metastasis, while developing countries like China developed quickly. Furthermore, the success of novel therapies in recent years may lead to the new era of treatment of breast cancer with brain metastasis in the future.
Associations of human papillomavirus genotypes and cervical vascular abnormality in a cohort of women underwent colposcopy, a retrospective study of 6716 patients
Authors: Zhang Yulong , Li Haibo , Li Xiaowen , Li Zhelong , You Qianru , Yi Huan , Su Yanzhao , Zheng Xiangqin , Chen Yusha , Chen Jiancui
Published: April 2023

Aims

Abnormal vessel patterns are specific signs in patients with early cervical abnormality and cervical cancer(CC) by colposcopy, but the impact of human papillomavirus (HPV) infections on abnormal vessel patterns remains unknown.

Methods

A total of 6716 female patients with HPV infections or cytological abnormalities who underwent a colposcopy following abnormal CC screening results were included in the study. The final pathological diagnosis was confirmed to be the most severe pathological grade across cervical biopsy, endocervical canal curettage (ECC) and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between HPV infections and abnormal vessel patterns, adjusting for age, gravidity and parity.

Results

There were 6124 normal vascular cases by colposcopy and 592 cases with cervical vascular abnormality. The prevalence of HPV infections was 4284 (70%) in normal patients, and the prevalence of HPV infections was 479 (80%) in cervical vascular abnormality patients. HPV high-risk type 16 infection alone increased the risk of cervical heteromorphic blood vessels (aOR=3.66, 95%CI: 2.54~5.27). HPV 16 and 33 alone (other than the commonly recognized subtype of 18) or coinfection of these two genotypes could increase the risk of cervical punctate vascular and cervical vascular mosaic features and abnormal cervical blood vessels. An increased risk of abnormal cervical lesions was observed for HPV 16 and 33 alone or combined in coinfection compared to the negative group. The risk of cervical vascular abnormality was increased 10-fold by coinfection with HPV 16 and 33 (aOR=10.67, 95% CI: 4.54~25.09, P<0.001). HPV 16, 33 alone or combined in coinfection were associated with an increased risk of lesions more advanced than high-grade squamous intraepithelial lesion (HSIL) when compared to the negative group. The risk of lesions more advanced than HSIL was up to 26-fold higher in the coinfection with HPV 16 and 33 group than in the negative group (aOR=26.23, 95%CI: 11.23~61.27, P<0.001).

Conclusion

HPV16 and 33 are the most dangerous HPV genotypes correlated with abnormal vascular patterns. Combined HPV16 and HPV33 infection increases the risk of abnormal vascular patterns. Combined HPV16 and HPV33 infection increases the risk of developing HSIL+.
Tislelizumab immunotherapy combined with chemotherapy in the treatment of a patient with primary anterior mediastinal undifferentiated pleomorphic sarcoma with high PD-L1 expression: A case report and literature review
Authors: Yang Hujuan , Qin Zhiquan , He Xianglei , Xue Qian , Zhou Hongying , Sun Jie , Li Xiaoyi , Zhao Tongwei
Published: April 2023

Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor with a high degree of malignancy and rapid progression, usually occurring in the extremities, retroperitoneum, and abdomen, whereas it rarely arises in the mediastinum, and is treated mainly by surgical resection. The prognosis of patients with advanced sarcoma is poor, and doxorubicin monotherapy is the standard first-line chemotherapy for most advanced soft tissue sarcomas (STS), but the prognosis is generally unsatisfactory. Immune checkpoint inhibitors (ICIs) have been established as therapies for many solid cancers in recent years; however, evidence on the efficacy of ICIs in undifferentiated sarcoma is scarce, mostly consisting of small studies, and no ICIs are currently approved for use in sarcomas. We report a case of a middle-aged man with primary mediastinal UPS with high PD-L1 expression (TPS was approximately 80%) and TLS positive. The patient was treated with sequential tislelizumab monotherapy maintenance after 6 cycles of tislelizumab combined with epirubicin, efficacy evaluation was partial remission (PR), progression-free survival (PFS) was 8.5 months, and grade 1 fatigue was identified as an adverse event.
Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy
Authors: Casadei-Gardini Andrea , Leone Francesco , Brandi Giovanni , Scartozzi Mario , Silvestris Nicola , Santini Daniele , Faloppi Luca , Aglietta Massimo , Satolli Maria Antonietta , Rizzo Alessandro , Lonardi Sara , Aprile Giuseppe , Fornaro Lorenzo
Published: April 2023

Cholangiocarcinoma is a rare group of tumors that involve the hepatic biliary tree. Prognosis for patients with cholangiocarcinoma remains dismal. Herein, we present survival trends over a long time period spanning almost 20 years in patients with advanced cholangiocarcinoma receiving systemic chemotherapy. We retrospectively analyzed a large multicenter dataset of cholangiocarcinoma outpatients evaluated in 14 centers within the Cholangiocarcinoma Italian Group Onlus (Gruppo Italiano Colangiocarcinoma Onlus, G.I.C.O.) between 2000 and 2017 (first-line), and 2002 and 2017 (second-line). Three time periods were considered: 2000-2009, 2010-2013, and 2014-2017. A total of 922 patients (51.19% male) with cholangiocarcinoma undergoing first-line therapy were evaluated. The median durations of follow-up for progression-free survival (PFS) and overall survival (OS) were 37 and 57 months, respectively. PFS at 12 months in the three periods of starting first-line therapy was similar, ranging from 11.71% to 15.25%. OS at 12 months progressively improved (38.30%, 44.61% and 49.52%, respectively), although the differences were not statistically significant after adjusting for age, disease status, and primary tumor site. A total of 410 patients (48.5% male) underwent second-line chemotherapy. The median durations of follow-up for PFS and OS were 47.6 and 41.90 months, respectively. An OS of 24.3%, 32.3%, and 33.1% was observed in 2002-2009, 2010-2013, and 2014-2017, respectively. Despite incremental benefits across years, our clinical experience confirms that modest overall advances have been achieved with first- and second-line chemotherapy in advanced cholangiocarcinoma. Efforts should focus on the identification of patients who derive the greatest benefit from treatment.
Erectile function, urinary continence and oncologic outcomes of neurovascular bundle sparing robot-assisted radical prostatectomy for high-risk prostate cancer: A systematic review and meta-analysis
Authors: Liu Yang , Deng Xian-zhong , Qin Jiao , Wen Zhi , Jiang Yu , Huang Jing , Wang Chong-jian , Chen Cai-xia , Wang Li , Li Kun-peng , Wang Jia-hao , Yang Xue-song
Published: April 2023

Background

The nerve-sparing (NS) effect of robot-assisted radical prostatectomy (RARP) on patients with a high-risk prostate cancer remains unclear. The objective of this study was to compare the urinary continence, erectile function and oncology outcomes of the nerve-sparing and non-nerve-sparing (NNS) group during RARP surgeries.

Methods

We systematically searched databases including PubMed, Embase, Cochrane Library and Web of Science to identify relevant studies published in English up to December 2022. Newcastle-Ottawa Scale (NOS) was used as a quality evaluation tool to evaluate the quality of the literature parameters involved, including urinary continence, erectile function and oncologic outcomes, which were compared using the Stata 15.1 software (StataSE, USA).

Results

A total of 8 cohort studies involving 2499 patients were included. A meta-analysis of results showed that the NS group was beneficial to the recovery of urinary continence (RR 0.46, 95%CI 0.22, 0.96; p=0.045<0.05) and erectile function (RR 0.32, 95%CI 0.16, 0.63; p=0.001<0.05) 12 months after surgeries, which showed a better oncological outcome (RR 1.31, 95%CI 1.01, 1.69; p=0.01<0.05).

Conclusions

The current study results indicate that intraoperative NS during RARP is beneficial to long-term postoperative functional recovery and tumor prognosis of patients with high-risk prostate cancers. Due to interstudy interferences, the results should be interpreted with caution.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022384647.
An integral approach to address Chagas disease
Authors: Gold Marina , Hermida Maria Julia
Published: April 2023

Chagas is a zoonotic disease conditioned by the need to eliminate or control the vector in human settlements before targeting infected individuals. Simultaneously it is necessary to raise awareness of health problems generated by chronic Chagas disease (ChD), for people to participate actively in vector control programs that will then enable the implementation of screening, treatment and follow-up strategies. Therefore, it is essential to engage the participation of the community in holistically designed integral programs to address ChD in all its complexity. This Perspective presents the case of Chagas management programs in the Department of General Taboada, Province of Santiago del Estero, Argentina, to showcase a possible strategy in vector control, diagnosis and treatment programs that integrate ChD into the local public health system and engage community participation. Through this Perspective we argue for the importance of the contribution of social science methodologies and epistemologies in the process of integrating ChD into the public (and primary) health care system.
Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction
Authors: Yu Siyi , Qian Hang , Tian Dawei , Yang Mingming , Li Dongfeng , Xu Hao , Chen Jishun , Yang Jingning , Hao Xincai , Liu Zhixin , Zhong Jixin , Yang Handong , Chen Xinlong , Min Xinwen , Chen Jun
Published: April 2023

Objective: To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms.

Methods: Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (n = 11), Linggui Zhugan Decoction group (n = 12), and captopril group (n = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (n = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction.

Results: Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (p < 0.05), reduced MDA production (p < 0.01), increased SOD activity (p < 0.05), reduced ST-2(p < 0.01), and NT-proBNP(p < 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes.

Conclusion: Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.
Potential adverse actions of prenatal exposure of acetaminophen to offspring
Authors: Wu Ka , Lu Wensheng , Yan Xin
Published: April 2023

Acetaminophen (APAP) is a widely used as analgesic and antipyretic drug. APAP is also added as an active ingredient in various medications to relieve pain and reduce fever. APAP has been widely used in pregnant women in the past decades because it is considered a relatively safe drug with recommended dose in different countries. However, an increasing number of epidemiological and experimental studies have shown that APAP exposure during pregnancy may increase the risk of inducing reproductive and neurobehavior dysfunctions, hepatotoxicity in offspring. This review aims to assess the potential effects of prenatal APAP exposure on offspring growth and development.
Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment
Authors: Huan Jia-Ming , Ma Xi-Ting , Li Si-Yi , Hu Dong-Qing , Chen Hao-Yu , Wang Yi-Min , Su Xiao-Yi , Su Wen-Ge , Wang Yi-Fei
Published: April 2023

Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action.

Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients’ symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism.

Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025–6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1β, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways.

Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.
Perovskite band engineering for high-performance X-ray detection
Authors: He Yichu , Wang Zeshu , Wang Zi , Dun Guan-Hua , Geng Xiangshun , Wang Chunlin , Du Jingbo , Guo Tianyu , Xie Dan , Tian He , Yang Yi , Ren Tian-Ling
Published: April 2023

Perovskite-based X-ray detector, which is widely applied in fields of scientific research and medical diagnosis, has drawn much attention for its superior optoelectrical properties. To improve the detection performance, band engineering is becoming the hot topic for perovskite properties modulation. In this article, we review the recent progress of perovskite-based X-ray detectors with band engineering process from three aspects, which are background introduction, band theory of heterojunction devices, and optimized electrode contact devices. Lastly, research status and strategies are summarized and perspectives of future progress are analyzed. We hope this review can provide constructive instructions and suggestions for future development of band engineering for perovskite-based high-performance X-ray detector.
Development of NbTi planar superconducting undulators at the IHEP
Authors: Wei Junhao , Yang Xiangchen , Chen Zilin , Zhang Xiangzhen , Bian Xiaojuan , Li Yuhui
Published: April 2023

Superconducting undulators (SCUs) have the advantages of generating stronger magnetic field and the radiation hardness compared to permanent magnet undulators. Therefore, SCUs are valuable to be applied in the free-electron lasers (FELs) driven by high-repetition-rate linear accelerators. The Insertion Device Group at the Institute of High Energy Physics (IHEP) in China started an R&D project to produce NbTi planar SCU prototypes with 15 mm period length. Several SCU prototypes, including short mock-ups, a 0.5-m-long SCU, and a 1.5-m-long SCU, have been successfully produced and cryogenic tested. The short mock-up coils were cooled by a liquid helium free cryostat to be quench trained at 4 K. The maximum current in the coils reached 500 A and the magnetic peak field exceed 1 T with 7 mm gap. The 0.5-m-long SCU was tested by using a vertical test system. The correction coils were confirmed with the ability in both correcting the magnetic field integrals and the phase error. The 1.5-m-long SCU was not only vertically tested, but also installed in a cryostat to be operated with high current over a long time. We applied the gap adjustment method to reduce the phase error within 9 degrees. The development of SCUs at the IHEP is introduced in this paper in detail.
Integrated 16S and metabolomics revealed the mechanism of drought resistance and nitrogen uptake in rice at the heading stage under different nitrogen levels
Authors: Sun Changhui , Wang Runnan , Tang Guoping , Cai Shuo , Shi Hong , Liu Fangping , Xie Hengwang , Zhu Jinyan , Xiong Qiangqiang
Published: April 2023

The normal methods of agricultural production worldwide have been strongly affected by the frequent occurrence of drought. Rice rhizosphere microorganisms have been significantly affected by drought stress. To provide a hypothetical basis for improving the drought resistance and N utilization efficiency of rice, the study adopted a barrel planting method at the heading stage, treating rice with no drought or drought stress and three different nitrogen (N) levels. Untargeted metabolomics and 16S rRNA gene sequencing technology were used to study the changes in microorganisms in roots and the differential metabolites (DMs) in rhizosphere soil. The results showed that under the same N application rate, the dry matter mass, N content and N accumulation in rice plants increased to different degrees under drought stress. The root soluble protein, nitrate reductase and soil urease activities were improved over those of the no-drought treatment. Proteobacteria, Bacteroidota, Nitrospirota and Zixibacteria were the dominant flora related to N absorption. A total of 184 DMs (98 upregulated and 86 downregulated) were identified between low N with no drought (LN) and normal N with no drought (NN); 139 DMs (83 upregulated and 56 downregulated) were identified between high N with no drought (HN) and NN; 166 DMs (103 upregulated and 63 downregulated) were identified between low N with drought stress (LND) and normal N with drought stress (NND); and 124 DMs (71 upregulated and 53 downregulated) were identified between high N with drought stress (HND) and NND. Fatty acyl was the metabolite with the highest proportion. KEGG analysis showed that energy metabolism pathways, such as D-alanine metabolism and the phosphotransferase system (PTS), were enriched. We conclude that N-metabolism enzymes with higher activity and higher bacterial diversity have a significant effect on drought tolerance and nitrogen uptake in rice.