bluuebunny/crossref_metadata_2025 huggingface dataset:
Time to initiation of antenatal care visit and its predictors among reproductive age women in Ethiopia: Gompertz inverse Gaussian shared frailty model
Authors: Belay Daniel Gashaneh , Alemu Melaku Birhanu , Aragaw Fantu Mamo , Asratie Melaku Hunie
Published: October 2023

Background

Early initiation of antenatal care (ANC) is essential for the early detection of pregnancy-related problems and unfavorable pregnancy outcomes. However, a significant number of mothers do not initiate ANC at the recommended time. Therefore, this study aimed to determine the median time of ANC initiation and its predictors among reproductive-age women in Ethiopia.

Methods

We used the Ethiopian Demographic and Health Survey (EDHS) 2016 data set. The proportional hazard assumption was assessed using Schoenfeld residual test and log–log plot. A life table was used to determine the median survival time (time of ANC initiation). The Gompertz inverse Gaussian shared frailty model was the best-fitting model for identifying the predictors for the early initiation of ANC booking. Finally, the adjusted hazard ratio (AHR) with a 95% confidence interval (CI) was used to determine the significance of predictors.

Results

A total of 7,501 reproductive-aged women gave recent birth in the last 5 years preceding the survey. Nearly three in five women [61.95% (95% CI: 60.85–63.04%)] booked their first ANC visit with a median time of 4.4 months. Women who attended primary education (AHR = 1.10, 95% CI: 1.01–1.20), secondary and above (AHR = 1.26, 95% CI: 1.11–1.44), media exposure (AHR = 1.07, 95% CI: 1.00–1.16), rich wealthy (AHR = 1.17, 95% CI: 1.06–1.30), grand multiparous (AHR = 0.82, 95% CI: 0.72–0.93), unwanted pregnancy (AHR = 0.88, 95% CI: 0.81–0.96), small periphery region (AHR = 0.58, 95% CI: 0.51–0.67), and rural residence (AHR = 0.86, 95% CI: 0.75–0.99) were significantly associated with first ANC visit.

Conclusion

According to this study, a significant number of women missed their first ANC visit. The education status of women, place of residence, region, wealth index, media exposure, unintended pregnancy, and multi-parity were significantly associated with the time of initiation of the first ANC visit. Therefore, policymakers should focus on improving the socioeconomic status (education, media coverage, and wealth) of reproductive-aged women by prioritizing women who live in small periphery regions and rural residences to improve the early initiation of ANC.
Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression
Authors: McCormick Amanda L. , Anderson Trevor S. , Daugherity Elizabeth A. , Okpalanwaka Izuchukwu F. , Smith Savanna L. , Appiah Duke , Lowe Devin B.
Published: October 2023

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer. Our pre-clinical data demonstrate the αDC1 vaccine’s ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.
Whole-genome bisulfite sequencing reveals the function of DNA methylation in the allotransplantation immunity of pearl oysters
Authors: Gu Zefeng , Yang Jingmiao , Lu Jinzhao , Yang Min , Deng Yuewen , Jiao Yu
Published: October 2023

Introduction

In the pearl culture industry, a major challenge is the overactive immunological response in pearl oysters resulting from allotransplantation, leading to shell-bead rejection and death. To better understand the molecular mechanisms of postoperative recovery and the regulatory role of DNA methylation in gene expression, we analyzed the changes in DNA methylation levels after allotransplantation in pearl oyster Pinctada fucata martensii, and elucidated the regulatory function of DNA methylation in promoter activity of nicotinic acetylcholine receptor (nAChR) gene.

Methods

We constructed nine DNA methylomes at different time points after allotransplantation and used bisulfite genomic sequencing PCR technology (BSP) to verify the methylation status in the promoter of nAChR. We performed Dual luciferase assays to determine the effect of the dense methylation region in the promoter on transcriptional activity and used DNA pull-down and mass spectrometry analysis to assess the capability of transcription factor binding with the dense methylation region.

Result

The DNA methylomes reveal that CG-type methylation is predominant, with a trend opposite to non-CG-type methylation. Promoters, particularly CpG island-rich regions, were less frequently methylated than gene function elements. We identified 5,679 to 7,945 differentially methylated genes (DMGs) in the gene body, and 2,146 to 3,385 DMGs in the promoter at each time point compared to the pre-grafting group. Gene ontology and pathway enrichment analyses showed that these DMGs were mainly associated with “cellular process”, “Membrane”, “Epstein-Barr virus infection”, “Notch signaling pathway”, “Fanconi anemia pathway”, and “Nucleotide excision repair”. Our study also found that the DNA methylation patterns of the promoter region of nAChR gene were consistent with the DNA methylomics data. We further demonstrated that the dense methylation region in the promoter of nAChR affects transcriptional activity, and that the methylation status in the promoter modulates the binding of different transcription factors, particularly transcriptional repressors.

Conclusion

These findings enhance our understanding of the immune response and regulation mechanism induced by DNA methylation in pearl oysters after allotransplantation.
Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro
Authors: Brauneck Franziska , Oliveira-Ferrer Leticia , Muschhammer Jana , Sturmheit Tabea , Ackermann Christin , Haag Friedrich , Schulze zur Wiesch Julian , Ding Yi , Qi Minyue , Hell Louisa , Schmalfeldt Barbara , Bokemeyer Carsten , Fiedler Walter , Wellbrock Jasmin
Published: October 2023

Introduction

Tumor-associated macrophages (TAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype and function of these cells. The present study aims to characterize macrophages in high-grade serous ovarian cancer (HGSOC).

Methods

Phenotype and expression of co-regulatory markers were assessed on TAMs derived from malignant ascites (MA) or peripheral blood (PB) by multiparametric flow cytometry. Samples were obtained from HGSOC patients (n=29) and healthy donors (HDs, n=16). Additional expression analysis was performed by RNAseq (n=192). Correlation with clinically relevant parameters was conducted and validated by a second patient cohort (n=517). Finally, the role of TIGIT in repolarization and phagocytosis was investigated in vitro.

Results

Expression of the M2-associated receptors CD163, CD204, and CD206, as well as of the co-regulatory receptors TIGIT, CD226, TIM-3, and LAG-3 was significantly more frequent on macrophages in HGSOC than in HDs. CD39 and CD73 were broadly expressed on (mainly M2) macrophages, but without a clear clustering in HGSOC. CD163 mRNA levels were higher in TAMs from patients with residual tumor mass after surgery and associated with a shorter overall survival. In addition, TIGIT expression was associated with a higher tumor grading, indicating a prognostic relevance of M2 infiltration in HGSOC. TIGIT blockade significantly reduced the frequency of M2 macrophages. Moreover, combined blockade of TIGIT and CD47 significantly increased phagocytosis of ovarian cancer cells by TAMs in comparison to a single blockade of CD47.

Conclusion

Combined blockade of TIGIT and CD47 represents a promising approach to enhance anti-CD47-facilitated phagocytosis.
The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature
Authors: Fejza Albina , Carobolante Greta , Poletto Evelina , Camicia Lucrezia , Schinello Giorgia , Di Siena Emanuele , Ricci Giuseppe , Mongiat Maurizio , Andreuzzi Eva
Published: October 2023

Introduction

Immune-checkpoint inhibitors (ICIs) have emerged as a core pillar of cancer therapy as single agents or in combination regimens both in adults and children. Unfortunately, ICIs provide a long-lasting therapeutic effect in only one third of the patients. Thus, the search for predictive biomarkers of responsiveness to ICIs remains an urgent clinical need. The efficacy of ICIs treatments is strongly affected not only by the specific characteristics of cancer cells and the levels of immune checkpoint ligands, but also by other components of the tumor microenvironment, among which the extracellular matrix (ECM) is emerging as key player. With the aim to comprehensively describe the relation between ECM and ICIs’ efficacy in cancer patients, the present review systematically evaluated the current literature regarding ECM remodeling in association with immunotherapeutic approaches.

Methods

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022351180). PubMed, Web of Science, and Scopus databases were comprehensively searched from inception to January 2023. Titles, abstracts and full text screening was performed to exclude non eligible articles. The risk of bias was assessed using the QUADAS-2 tool.

Results

After employing relevant MeSH and key terms, we identified a total of 5070 studies. Among them, 2540 duplicates, 1521 reviews or commentaries were found and excluded. Following title and abstract screening, the full text was analyzed, and 47 studies meeting the eligibility criteria were retained. The studies included in this systematic review comprehensively recapitulate the latest observations associating changes of the ECM composition following remodeling with the traits of the tumor immune cell infiltration. The present study provides for the first time a broad view of the tight association between ECM molecules and ICIs efficacy in different tumor types, highlighting the importance of ECM-derived proteolytic products as promising liquid biopsy-based biomarkers to predict the efficacy of ICIs.

Conclusion

ECM remodeling has an important impact on the immune traits of different tumor types. Increasing evidence pinpoint at ECM-derived molecules as putative biomarkers to identify the patients that would most likely benefit from ICIs treatments.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351180, identifier CRD42022351180.
Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1
Authors: Hioe Catarina E. , Liu Xiaomei , Banin Andrew N. , Heindel Daniel W. , Klingler Jéromine , Rao Priyanka G. , Luo Christina C. , Jiang Xunqing , Pandey Shilpi , Ordonez Tracy , Barnette Philip , Totrov Maxim , Zhu Jiang , Nádas Arthur , Zolla-Pazner Susan , Upadhyay Chitra , Shen Xiaoying , Kong Xiang-Peng , Hessell Ann J.
Published: October 2023

Introduction

Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge.

Objective

This study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env).

Methods

Four groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope in vitro.

Results

Rabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses.

Conclusion

These data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158.
CD44v6, STn & O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies
Authors: Lodewijk Iris , Dueñas Marta , Paramio Jesus M. , Rubio Carolina
Published: October 2023

Targeted therapies are the state of the art in oncology today, and every year new Tumor-associated antigens (TAAs) are developed for preclinical research and clinical trials, but few of them really change the therapeutic scenario. Difficulties, either to find antigens that are solely expressed in tumors or the generation of good binders to these antigens, represent a major bottleneck. Specialized cellular mechanisms, such as differential splicing and glycosylation processes, are a good source of neo-antigen expression. Changes in these processes generate surface proteins that, instead of showing decreased or increased antigen expression driven by enhanced mRNA processing, are aberrant in nature and therefore more specific targets to elicit a precise anti-tumor therapy. Here, we present promising TAAs demonstrated to be potential targets for cancer monitoring, targeted therapy and the generation of new immunotherapy tools, such as recombinant antibodies and chimeric antigen receptor (CAR) T cell (CAR-T) or Chimeric Antigen Receptor-Engineered Natural Killer (CAR-NK) for specific tumor killing, in a wide variety of tumor types. Specifically, this review is a detailed update on TAAs CD44v6, STn and O-GD2, describing their origin as well as their current and potential use as disease biomarker and therapeutic target in a diversity of tumor types.
Impacts of climate events on life history parameters of major commercial fishes in the Beibu Gulf, South China Sea in the last 15 years
Authors: Hong Xiaofan , Zhang Kui , Li Jiajun , Xu Youwei , Sun Mingshuai , Jiang Jingyuan , Xu Shannan , Cai Yancong , Qiu Yongsong , Chen Zuozhi
Published: October 2023

A detailed understanding of the impact of climate variability on fish life histories provides a fundamental basis for the ecosystem approach to fisheries management. In this study, we evaluated the relationship between fish life-history trait parameters and climate periods, using survey data from 2006−2020 for the Beibu Gulf of the northwestern South China Sea, a fishing ground with high commercial and ecological value. We show that climate events can significantly alter the structure of the life history for major commercial fishes, with more diverse life-history strategies during warm events and more concentrated mortality during cold events. Additionally, we detected special relationships between climate events and the life-history trait composite index (LTCI) inPsenopsis anomalaandTrichiurus lepturus. It is possible that other indicators would be more appropriate than variability in Oceanic Niño Index (ONI), such as variation in fishing effort or the environmental resistance of fish. Anthropogenic disturbance and biological features may also help explain the magnitude of population variability. We found that changes in life-history traits of only a few commercial fishes (Decapterus maruadsi,Pennahia macrocephalus, andUpeneus sulphureus) were related to the shift in climate periods; these fishes were generally characterized by faster growth and higher mortality rates in the normal and El Niño periods, with the opposite trends in La Niña periods. However, the emergence of climate events has led to a clear complementarity of life-history strategies among some fish in the same ecological niche (same genus and/or feeding group), which may be explained by a balance between habitat conditions and fishing pressures. This study of fish life-history strategies under climate anomalies provides key insights into important attributes for managers to consider when implementing relevant measures to promote fisheries sustainability in the subtropical bay.
Investigation on permanent deformation in steel-concrete composite beam bridge deck pavement under temperature-load coupling effect
Authors: Yang Jing , Tan Liming , Qi Xiangyu , Zhang Chenchen
Published: October 2023

Rutting is one of the common distresses observed in asphalt pavement, influenced by temperature and load conditions. To clarify the permanent deformation behavior of steel-concrete composite beam (SCCB) bridge deck pavement under temperature-load coupling effect and provide references for the distress cause analysis, five typical SCCB bridge deck pavements were selected. The temperature distribution and the temperature stress of the pavement structures were analyzed by numerical simulation under periodic temperature variations. In addition, considering the daily variation in traffic volume, the permanent deformation of the five pavement structures were calculated under temperature-load coupling effect. Finally, the influence of heavy load on the development of rutting distress was also investigated. The results show that the temperature field and temperature stresses within the SCCB bridge deck pavement exhibit periodic variations under periodic temperature variations. Additionally, after 500,000 times of standard axle load application, “EA + SMA” exhibits the smallest permanent deformation and the best resistance to rutting distress under temperature-load coupling effect. Finally, heavy load conditions have a great influence on the permanent deformation of SCCB bridge deck pavement. In areas with severe rutting distresses, it is recommended to use “EA + SMA” pavement structure in SCCB bridge.
Metasurface-enabled electromagnetic illusion with generic algorithm
Authors: Zhu Rongrong , Chen Tianhang , Wang Kai , Wu Hao , Lu Huan
Published: October 2023

Electromagnetic cloak or illusion, which can interfere with device detection and provide superior self-protection capabilities for animals or humans, has received much attention. The proposal of transformation optics provides a generalized strategy for realizing electromagnetic illusion. However, the complex parameter composition causes a substantial computational cost, which is not conducive to practical applications. To overcome these challenges, we report an intelligent illusory metasurface optimized by a genetic algorithm, which not only presents predefined illusory effects but also reduces the parameter space in physics. By designing a high-performance tunable metasurface, a high-fidelity inverse design is performed in simulation. Near-field and far field results show that the metasurface can generate virtual targets in different scenarios and realize electromagnetic illusion. This work is helpful in facilitating the practical application of electromagnetic illusion strategies.
Application of the endogenous CRISPR-Cas type I-D system for genetic engineering in the thermoacidophilic archaeon Sulfolobus acidocaldarius
Authors: Bost Jan , Recalde Alejandra , Waßmer Bianca , Wagner Alexander , Siebers Bettina , Albers Sonja-Verena
Published: October 2023

CRISPR (clustered regularly interspaced short palindromic repeats)-Cas systems are widely distributed among bacteria and archaea. In this study, we demonstrate the successful utilization of the type I-D CRISPR-Cas system for genetic engineering in the thermoacidophilic archaeon Sulfolobus acidocaldarius. Given its extreme growth conditions characterized by a temperature of 75°C and pH 3, an uracil auxotrophic selection system was previously established, providing a basis for our investigations. We developed a novel plasmid specifically designed for genome editing, which incorporates a mini-CRISPR array that can be induced using xylose, resulting in targeted DNA cleavage. Additionally, we integrated a gene encoding the β-galactosidase of Saccharolobus solfataricus into the plasmid, enabling blue-white screening and facilitating the mutant screening process. Through the introduction of donor DNA containing genomic modifications into the plasmid, we successfully generated deletion mutants and point mutations in the genome of S. acidocaldarius. Exploiting the PAM (protospacer adjacent motif) dependence of type I systems, we experimentally confirmed the functionality of three different PAMs (CCA, GTA, and TCA) through a self-targeting assessment assay and the gene deletion of upsE. Our findings elucidate the application of the endogenous Type I-D CRISPR-Cas system for genetic engineering in S. acidocaldarius, thus expanding its genetic toolbox.
Recent advances in the biodegradation of polyethylene terephthalate with cutinase-like enzymes
Authors: Sui Beibei , Wang Tao , Fang Jingxiang , Hou Zuoxuan , Shu Ting , Lu Zhenhua , Liu Fei , Zhu Youshuang
Published: October 2023

Polyethylene terephthalate (PET) is a synthetic polymer in the polyester family. It is widely found in objects used daily, including packaging materials (such as bottles and containers), textiles (such as fibers), and even in the automotive and electronics industries. PET is known for its excellent mechanical properties, chemical resistance, and transparency. However, these features (e.g., high hydrophobicity and high molecular weight) also make PET highly resistant to degradation by wild-type microorganisms or physicochemical methods in nature, contributing to the accumulation of plastic waste in the environment. Therefore, accelerated PET recycling is becoming increasingly urgent to address the global environmental problem caused by plastic wastes and prevent plastic pollution. In addition to traditional physical cycling (e.g., pyrolysis, gasification) and chemical cycling (e.g., chemical depolymerization), biodegradation can be used, which involves breaking down organic materials into simpler compounds by microorganisms or PET-degrading enzymes. Lipases and cutinases are the two classes of enzymes that have been studied extensively for this purpose. Biodegradation of PET is an attractive approach for managing PET waste, as it can help reduce environmental pollution and promote a circular economy. During the past few years, great advances have been accomplished in PET biodegradation. In this review, current knowledge on cutinase-like PET hydrolases (such as TfCut2, Cut190, HiC, and LCC) was described in detail, including the structures, ligand–protein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts were highlighted, such as improving the PET hydrolytic activity by constructing fusion proteins. The review is expected to provide novel insights for the biodegradation of complex polymers.
Dynamics and ecological reassembly of the human gut microbiome and the host metabolome in response to prolonged fasting
Authors: Sang Xiaopu , Li Shenghui , Guo Ruochun , Yan Qiulong , Liu Changxi , Zhang Yue , Lv Qingbo , Wu Lili , Ma Jie , You Wei , Feng Ling , Sun Wen
Published: October 2023

Introduction

Prolonged fasting is an intervention approach with potential benefits for individuals with obesity or metabolic disorders. Changes in gut microbiota during and after fasting may also have significant effects on the human body.

Methods

Here we conducted a 7-days medically supervised water-only fasting for 46 obese volunteers and characterized their gut microbiota based on whole-metagenome sequencing of feces at five timepoints.

Results

Substantial changes in the gut microbial diversity and composition were observed during fasting, with rapid restoration after fasting. The ecological pattern of the microbiota was also reassembled during fasting, reflecting the reduced metabolic capacity of diet-derived carbohydrates, while other metabolic abilities such as degradation of glycoproteins, amino acids, lipids, and organic acid metabolism, were enhanced. We identified a group of species that responded significantly to fasting, including 130 fasting-resistant (consisting of a variety of members of Bacteroidetes, Proteobacteria, and Fusobacteria) and 140 fasting-sensitive bacteria (mainly consisting of Firmicutes members). Functional comparison of the fasting-responded bacteria untangled the associations of taxon-specific functions (e.g., pentose phosphate pathway modules, glycosaminoglycan degradation, and folate biosynthesis) with fasting. Furthermore, we found that the serum and urine metabolomes of individuals were also substantially changed across the fasting procedure, and particularly, these changes were largely affected by the fasting-responded bacteria in the gut microbiota.

Discussion

Overall, our findings delineated the patterns of gut microbiota alterations under prolonged fasting, which will boost future mechanistic and clinical intervention studies.
Enhancing remediation potential of heavy metal contaminated soils through synergistic application of microbial inoculants and legumes
Authors: Zheng Kang , Liu Zexun , Liu Chao , Liu Jiayi , Zhuang Jiayao
Published: October 2023

Soil microorganisms play a crucial role in remediating contaminated soils in modern ecosystems. However, the potential of combining microorganisms with legumes to enhance the remediation of heavy metal-contaminated soils remains unexplored. To investigate this, we isolated and purified a highly efficient cadmium and lead-tolerant strain. Through soil-cultivated pot experiments with two leguminous plants (Robinia pseudoacacia L. and Sophora xanthantha), we studied the effects of applying this microbial agent on plant nutrient uptake of soil nutrients, heavy metal accumulation, and the dynamics of heavy metal content. Additionally, we examined the response characteristics of inter-root microbial and bacterial communities. The results demonstrated that microorganisms screened from heavy metal-contaminated soil environments exhibited strong survival and adaptability in heavy metal solutions. The use of the Serratia marcescens WZ14 strain-phytoremediation significantly increased the soil’s ammonium nitrogen (AN) and organic carbon (OC) contents compared to monoculture. In addition, the lead (Pb) and cadmium (Cd) contents of the soil significantly decreased after combined remediation than those of the soil before potting. However, the remediation effects on Pb- and Cd-contaminated soils differed between the two legumes following the Serratia marcescens WZ14 inoculation. The combined restoration altered the composition of the plant inter-rhizosphere bacterial community, with the increase in the relative abundance of both Proteobacteria and Firmicutes. Overall, the combined remediation using the tolerant strain WZ14 with legumes proved advantageous. It effectively reduced the heavy metal content of the soil, minimized the risk of heavy metal migration, and enhanced heavy metal uptake, accumulation, and translocation in the legumes of S. xanthantha and R. pseudoacacia. Additionally, it improved the adaptability and resistance of both legumes, leading to an overall improvement in the soil’s environmental quality. These studies can offer primary data and technical support for remediating and treating Cd and Pb in soils, as well as rehabilitating mining sites.
The impact of Helicobacter pylori eradication with vonoprazan-amoxicillin dual therapy combined with probiotics on oral microbiota: a randomized double-blind placebo-controlled trial
Authors: Peng Ruolin , Zhang Zhenyu , Qu Yi , Chen Weiwei
Published: October 2023

Background

Helicobacter pylori infection and eradication have been reported to cause dysbiosis of the oral microbiota. Probiotics are increasingly being used to maintain the balance of the oral microbiota. We aimed to investigate the effects of H. pylori infection, H. pylori eradication with vonoprazan-amoxicillin dual therapy, and probiotics supplementation on the oral microbiota.

Methods

H. pylori positive patients were randomly assigned to a vonoprazan-amoxicillin regimen plus probiotics (BtT group) or the placebo (PT group) for 14 days. H. pylori negative population served as normal controls. Tongue coating samples were collected from 60 H. pylori positive patients at three time points (before H. pylori eradication, after H. pylori eradication, and at confirmation of H. pylori infection cure) and 20 H. pylori negative subjects. 16S rRNA gene sequencing was used to analyze the oral microbiota.

Results

H. pylori was detected in the oral cavity in positive (34/60), negative (7/20), and eradicated (1/60) subjects using high-throughput sequencing. Compared with normal controls, H. pylori positive patients exhibited higher richness (p = 0.012) and comparable diversity (p = 0.075) of oral microbiota. Beta diversity and KEGG analysis showed oral flora composition and function differences in H. pylori positive and negative subjects. Alpha diversity dramatically decreased after H. pylori eradication and modestly increased with confirmation of H. pylori eradication. Beta diversity and LEfSe analysis revealed distinct structures, and KEGG analysis showed distinct signaling pathways of tongue coating flora at three time points. There was a significant reduction of Firmicutes and Lactobacillus after H. pylori erdication. The PT group and BtT group had identical compositional and functional differences of oral microbiota at three time points.

Conclusion

No substantial link existed between oral and stomach H. pylori, while removing gastric H. pylori helped eliminate oral H. pylori. H. pylori infection and vonoprazan-amoxicillin dual therapy affected oral microbiota diversity, structure, and function. H. pylori eradication demonstrated a suppressive impact on the proliferation of oral pathogens, specifically Firmicutes and Lactobacillus. Nevertheless, probiotics supplementation did not reduce the oral microbial disturbance caused by H. pylori eradication.

Clinical trial registration

https://www.chictr.org.cn/, identifiers CHICTR2200060023.
Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases?
Authors: Zhao Yifan , Li Cheng , Zhang Shuai , Cheng Jiayu , Liu Yucheng , Han Xiaorong , Wang Yinghui , Wang Yonggang
Published: October 2023

Nitric oxide (NO), as an important gaseous medium, plays a pivotal role in the human body, such as maintaining vascular homeostasis, regulating immune-inflammatory responses, inhibiting platelet aggregation, and inhibiting leukocyte adhesion. In recent years, the rapid prevalence of coronavirus disease 2019 (COVID-19) has greatly affected the daily lives and physical and mental health of people all over the world, and the therapeutic efficacy and resuscitation strategies for critically ill patients need to be further improved and perfected. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator, and some studies have demonstrated its potential therapeutic use for COVID-19, severe respiratory distress syndrome, pulmonary infections, and pulmonary hypertension. In this article, we describe the biochemistry and basic characteristics of NO and discuss whether iNO can act as a “savior” for COVID-19 and related respiratory and cardiovascular disorders to exert a potent clinical protective effect.
Prevalence of cerebral palsy comorbidities in China: a systematic review and meta-analysis
Authors: Gong Chao , Liu Xiaopei , Fang Liya , Liu Annan , Lian Beibei , Qi Xunzhong , Chen Shuyue , Li Huiqing , Zhao Ming , Guo Jin , Zhou Shaobo
Published: October 2023

Objectives

This systematic review aimed to comprehensively understand the comorbidity of cerebral palsy (CP) in China.

Methods

We searched through databases in both Chinese and English until December 2022 to gather cross-sectional studies on the comorbidity of CP in China. After two reviewers independently screened the articles, collected the data, and assessed the bias risk, a meta-analysis was conducted using the Stata 17.0 software.

Results

A total of 73 articles were included. Of these, 16 articles reported total comorbidity, with a prevalence of 79.7% (95% CI: 73.8–85.7%); 56 articles reported epilepsy, with a prevalence of 17.9% (95% CI: 15.4–20.4%); 48 articles reported intellectual disability, with a prevalence of 58.0% (95% CI: 51.8–64.3%); 32 articles reported speech disorders, with a prevalence of 48.0% (95% CI: 41.6–54.4%); 41 articles reported hearing disorders, with a prevalence of 17.2% (95% CI: 13.0–21.4%); and 35 articles reported vision disorders, with a prevalence of 23.1% (95% CI: 16.3–29.8%). The topographical type of CP was the primary source of heterogeneity in the prevalence of epilepsy. Diagnostic criteria for CP, clinical type of CP, GMFCS, publishing time, and topographical type of CP were the primary sources of heterogeneity in the prevalence of intellectual disability. Clinical type of CP and topographical type were the primary sources of heterogeneity in the prevalence of speech disorders. Finally, the region was the primary source of heterogeneity in the prevalence of hearing disorders.

Conclusion

The prevalence of comorbidities in CP is high in China. Comorbidities are related to the characteristics, severity, and risk factors of brain insult and have a particular relationship with regional economic development and medical and health levels.
Itch: from the skin to the brain – peripheral and central neural sensitization in chronic itch
Authors: Mahmoud Omar , Oladipo Olusola , Mahmoud Rami H. , Yosipovitch Gil
Published: October 2023

Similar to chronic pain, chronic itch is frequently linked to neural sensitization, a phenomenon wherein the nervous system becomes hypersensitive to stimuli. This process of neural sensitization of chronic itch is orchestrated by various signaling pathways and mediators in both the peripheral and central nervous systems. At the level of the peripheral nervous system, inflammation and neuroimmune interactions induce plastic changes to peripheral nerve fibers, thereby amplifying the transmission of itch signaling. Neural sensitization in the central nervous system occurs at both the spinal cord and brain levels. At the level of the spinal cord, it involves hyperactivity of itch-activating spinal pathways, dysfunction of spinal inhibitory circuits, and attenuation of descending supraspinal inhibitory pathways. In the brain, neural sensitization manifests as structural and functional changes to itch-associated brain areas and networks. Currently, we have a diverse array of neuroimmune-modulating therapies targeting itch neural sensitization mechanisms to help with providing relief to patients with chronic itch. Itch research is a dynamic and continually evolving field, and as we grow in our understanding of chronic itch mechanisms, so will our therapeutic toolbox. Further studies exploring the peripheral and central neural sensitization mechanisms in the context of chronic itch are needed.
Amino acid profiles, disease activity, and protein intake in adult patients with Crohn’s disease
Authors: Cioffi Iolanda , Di Vincenzo Olivia , Imperatore Nicola , Fisco Mariagrazia , Testa Anna , Scialò Filippo , Castiglione Fabiana , Ruoppolo Margherita , Pasanisi Fabrizio , Santarpia Lidia
Published: October 2023

Introduction

Crohn’s disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with a relapsing–remitting course. Amino acids (AAs) may play critical roles in the intestinal manifestations of disease, due to their involvement in many metabolic and immune functions. The present study aimed to explore serum AA concentrations in adult patients with CD, looking into their variations due to disease activity, surgery and protein content of diet. Eventually, the link between AAs and inflammatory markers was also assessed.

Methods

Consecutive adult patients aged 18–65 years with diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record to assess protein intake. Disease activity was clinically defined using the Crohn’s Disease Activity Index (CDAI), while blood samples were taken to analyze serum AA profile and inflammatory markers.

Results

A total of 103 patients with CD (61 men and 42 women; age:39.9 ± 13.9 years, BMI: 23.4 ± 3.51 kg/m2) were included. Tryptophan levels were found to be remarkably decreased in most subjects, unrelated to disease activity. On the contrary, concentration of lysine, leucine, valine and glutamine decreased in active versus quiescent CD patients, while aspartic acid, glutamate and glycine increased. The latter AAs were also directly correlated with CDAI and serum interleukin (IL)- 1β concentration. Considering the total protein intake, expressed as g/kg/body weight, we observed a reduction in some essential AAs in patients with unmet protein requirements compared to patients who met the recommendation.

Discussion

In conclusion, specific AAs varied according to disease activity and protein intake, adjusted to body weight and disease status. Glu and Asp concentrations raised with increasing IL-1β. However, extensive research is needed to understand the mechanisms underpinning the link between variation in serum AAs, disease activity and protein intake in patients with CD.
A mixture of Nordic berries improves cognitive function, metabolic function and alters the gut microbiota in C57Bl/6J male mice
Authors: Huang Fang , Marungruang Nittaya , Martinsson Isak , Camprubí Ferrer Lluís , Nguyen Thao Duy , Gondo Thamani Freedom , Karlsson Eva Nordberg , Deierborg Tomas , Öste Rickard , Heyman-Lindén Lovisa
Published: October 2023

Our diets greatly influence our health. Multiple lines of research highlight the beneficial properties of eating berries and fruits. In this study, a berry mixture of Nordic berries previously identified as having the potential to improve memory was supplemented to young C57Bl/6J male mice to investigate effects on cognition function, metabolic health, markers of neuroinflammation, and gut microbiota composition. C57Bl/6J male mice at the age of 8 weeks were given standard chow, a high-fat diet (HF, 60%E fat), or a high-fat diet supplemented with freeze-dried powder (20% dwb) of a mixture of Nordic berries and red grape juice (HF + Berry) for 18 weeks (n = 12 animals/diet group). The results show that supplementation with the berry mixture may have beneficial effects on spatial memory, as seen by enhanced performance in the T–maze and Barnes maze compared to the mice receiving the high-fat diet without berries. Additionally, berry intake may aid in counteracting high-fat diet induced weight gain and could influence neuroinflammatory status as suggested by the increased levels of the inflammation modifying IL-10 cytokine in hippocampal extracts from berry supplemented mice. Furthermore, the 4.5-month feeding with diet containing berries resulted in significant changes in cecal microbiota composition. Analysis of cecal bacterial 16S rRNA revealed that the chow group had significantly higher microbial diversity, as measured by the Shannon diversity index and total operational taxonomic unit richness, than the HF group. The HF diet supplemented with berries resulted in a strong trend of higher total OTU richness and significantly increased the relative abundance of Akkermansia muciniphila, which has been linked to protective effects on cognitive decline. In conclusion, the results of this study suggest that intake of a Nordic berry mixture is a valuable strategy for maintaining and improving cognitive function, to be further evaluated in clinical trials.
Prognostic significance of the pretreatment pan-immune-inflammation value in cancer patients: an updated meta-analysis of 30 studies
Authors: Hai-Jing Yu , Shan Ren , Jie-Qiong Xia
Published: October 2023

Background

The pan-immune-inflammation value (PIV) has been reported as a promising prognostic biomarker in multiple cancers but still remains inconclusive. The objective of this study is to systematically investigate the association of the pretreatment PIV with survival outcomes in cancer patients, based on available literature.

Methods

Online databases including PubMed, Embase and the Web of Science were thoroughly searched for studies evaluating the prognostic role of the pretreatment PIV in cancers from the inception to June 2023. Hazard ratios (HRs) with 95% confidence intervals (CIs) were always assessed using a random-effects model. Statistical analyses were performed using Stata 12.0.

Results

Thirty studies were finally included after comprehensively study searching. In total, 8,799 cancer patients were enrolled in this meta-analysis. The pooled results demonstrated that patients in the high PIV group had a significantly poorer overall survival (HR = 2.07; 95%CI: 1.77–2.41; I2 = 73.0%) and progression-free survival (HR = 1.83; 95%CI: 1.37–2.45; I2 = 98.2%) than patients in the low PIV group. The prognostic significance of the PIV score on overall survival and progression-free survival was observed across various geographical regions, tumor stages and treatment strategies. Sensitivity analyses supported the stability of the above combined results.

Conclusion

This meta-analysis demonstrated that the pretreatment PIV could be a non-invasive and efficacious prognostic biomarker for cancer patients.
Clinical outcomes after online adaptive MR-guided stereotactic body radiotherapy for pancreatic tumors on a 1.5 T MR-linac
Authors: Eijkelenkamp Hidde , Grimbergen Guus , Daamen Lois A. , Heerkens Hanne D. , van de Ven Saskia , Mook Stella , Meijer Gert J. , Molenaar Izaak Q. , van Santvoort Hjalmar C. , Paulson Eric , Erickson Beth Ann , Verkooijen Helena M. , Hall William Adrian , Intven Martijn P. W.
Published: October 2023

Introduction

Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT.

Methods

We evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3–12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan–Meier analysis to calculate the cumulative overall survival.

Results

A total of 80 patients were assessed with a median FU of 8 months (range 1–39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3–4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3–4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%.

Conclusion

Online adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3–4 toxicity and a stable QoL at 3 months of FU.
MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis
Authors: Rezaee Aryan , Ahmadpour Sara , Jafari Ameneh , Aghili Sarehnaz , Zadeh Seyed Saeed Tamehri , Rajabi Ali , Raisi Arash , Hamblin Michael R. , Mahjoubin-Tehran Maryam , Derakhshan Marzieh
Published: October 2023

Gynecologic cancer is a significant cause of death in women worldwide, with cervical cancer, ovarian cancer, and endometrial cancer being among the most well-known types. The initiation and progression of gynecologic cancers involve a variety of biological functions, including angiogenesis and metastasis—given that death mostly occurs from metastatic tumors that have invaded the surrounding tissues. Therefore, understanding the molecular pathways underlying gynecologic cancer metastasis is critical for enhancing patient survival and outcomes. Recent research has revealed the contribution of numerous non-coding RNAs (ncRNAs) to metastasis and invasion of gynecologic cancer by affecting specific cellular pathways. This review focuses on three types of gynecologic cancer (ovarian, endometrial, and cervical) and three kinds of ncRNAs (long non-coding RNAs, microRNAs, and circular RNAs). We summarize the detailed role of non-coding RNAs in the different pathways and molecular interactions involved in the invasion and metastasis of these cancers.