bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic engineering for the production of acetoin and 2,3-butanediol at elevated temperature in Parageobacillus thermoglucosidasius NCIMB 11955
Authors: Sheng Lili , Madika Abubakar , Lau Matthew S. H. , Zhang Ying , Minton Nigel P.
Published: May 2023

The current climate crisis has emphasised the need to achieve global net-zero by 2050, with countries being urged to set considerable emission reduction targets by 2030. Exploitation of a fermentative process that uses a thermophilic chassis can represent a way to manufacture chemicals and fuels through more environmentally friendly routes with a net reduction in greenhouse gas emissions. In this study, the industrially relevant thermophile Parageobacillus thermoglucosidasius NCIMB 11955 was engineered to produce 3-hydroxybutanone (acetoin) and 2,3-butanediol (2,3-BDO), organic compounds with commercial applications. Using heterologous acetolactate synthase (ALS) and acetolactate decarboxylase (ALD) enzymes, a functional 2,3-BDO biosynthetic pathway was constructed. The formation of by-products was minimized by the deletion of competing pathways surrounding the pyruvate node. Redox imbalance was addressed through autonomous overexpression of the butanediol dehydrogenase and by investigating appropriate aeration levels. Through this, we were able to produce 2,3-BDO as the predominant fermentation metabolite, with up to 6.6 g/L 2,3-BDO (0.33 g/g glucose) representing 66% of the theoretical maximum at 50°C. In addition, the identification and subsequent deletion of a previously unreported thermophilic acetoin degradation gene (acoB1) resulted in enhanced acetoin production under aerobic conditions, producing 7.6 g/L (0.38 g/g glucose) representing 78% of the theoretical maximum. Furthermore, through the generation of a ΔacoB1 mutant and by testing the effect of glucose concentration on 2,3-BDO production, we were able to produce 15.6 g/L of 2,3-BDO in media supplemented with 5% glucose, the highest titre of 2,3-BDO produced in Parageobacillus and Geobacillus species to date.
Rapid automated antifungal susceptibility testing system for yeasts based on growth characteristics
Authors: Yu Jinhan , He Chun , Wang Tong , Zhang Ge , Li Jin , Zhang Jingjia , Kang Wei , Xu Yingchun , Zhao Ying
Published: May 2023

Fungal pathogens are a major threat to public health, as they are becoming increasingly common and resistant to treatment, with only four classes of antifungal medicines currently available and few candidates in the clinical development pipeline. Most fungal pathogens lack rapid and sensitive diagnostic techniques, and those that exist are not widely available or affordable. In this study, we introduce a novel automated antifungal susceptibility testing system, Droplet 48, which detects the fluorescence of microdilution wells in real time and fits growth characteristics using fluorescence intensity over time. We concluded that all reportable ranges of Droplet 48 were appropriate for clinical fungal isolates in China. Reproducibility within ±2 two-fold dilutions was 100%. Considering the Sensititre YeastOne Colorimetric Broth method as a comparator method, eight antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, anidulafungin, amphotericin B, and 5-flucytosine) showed an essential agreement of >90%, except for posaconazole (86.62%). Category agreement of four antifungal agents (fluconazole, caspofungin, micafungin, and anidulafungin) was >90%, except for voriconazole (87.93% agreement). Two Candida albicans isolates and anidulafungin showed a major discrepancy (MD) (2.60%), and no other MD or very MD agents were found. Therefore, Droplet 48 can be considered as an optional method that is more automated and can obtain results and interpretations faster than previous methods. However, the optimization of the detection performance of posaconazole and voriconazole and promotion of Droplet 48 in clinical microbiology laboratories still require further research involving more clinical isolates in the future.
Non-invasive cardiac kinetic energy distribution: a new marker of heart failure with impaired ejection fraction (KINO-HF)
Authors: De Keyzer Eva , Hossein Amin , Rabineau Jeremy , Morissens Marielle , Almorad Alexandre , van de Borne Philippe
Published: May 2023

Background

Heart failure (HF) remains a major cause of mortality, morbidity, and poor quality of life. 44% of HF patients present impaired left ventricular ejection fraction (LVEF). Kinocardiography (KCG) technology combines ballistocardiography (BCG) and seismocardiography (SCG). It estimates myocardial contraction and blood flow through the cardiac chambers and major vessels through a wearable device. Kino-HF sought to evaluate the potential of KCG to distinguish HF patients with impaired LVEF from a control group.

Methods

Successive patients with HF and impaired LVEF (iLVEF group) were matched and compared to patients with normal LVEF ≥ 50% (control). A 60 s KCG acquisition followed cardiac ultrasound. The kinetic energy from KCG signals was computed in different phases of the cardiac cycle (iKsystolic;ΔiKdiastolic) as markers of cardiac mechanical function.

Results

Thirty HF patients (67 [59; 71] years, 87% male) were matched with 30 controls (64.5 [49; 73] years, 87% male). SCG ΔiKdiastolic, BCG iKsystolic, BCG ΔiKdiastolic were lower in HF than controls (p < 0.05), while SCG iKsystolic was similar. Furthermore, a lower SCG iKsystolic was associated with an increased mortality risk during follow-up.

Conclusions

KINO-HF demonstrates that KCG can distinguish HF patients with impaired systolic function from a control group. These favorable results warrant further research on the diagnostic and prognostic capabilities of KCG in HF with impaired LVEF.

Clinical Trial Registration: NCT03157115.
Association of blood pressure variability and CT-based Leiden score in hypertension patients
Authors: Chen Jianqiao , Ji Xinqiang , Zhao Runtao , Wang Fan
Published: May 2023

Background

Blood pressure variability (BPV) obtained from ambulatory blood pressure monitoring (ABPM) has been demonstrated to accurately predict the risk of cerebrovascular events and death in hypertension patients, however, the association between BPV and the severity of coronary atherosclerotic plaque remains unclear.

Methods

Patients with hypertension combined with suspected coronary artery disease (CAD) were collected, who underwent both ABPM and coronary computed tomographic angiography (CCTA) from December 2017 to March 2022. Patients were divided into three groups according to the Leiden score: low-risk group (Leiden score <5), medium-risk group (Leiden score 5–20), and high-risk group (Leiden score >20). The clinical characteristics of patients were collected and analyzed. Univariate Pearson correlation and multivariate Logistics regression were used to determine the association between BPV and the severity of coronary atherosclerotic plaque.

Results

A total of 783 patients were included, with the average age of (62.85 ± 10.17) years and 523 males. Patients in the high-risk group had higher mean systolic blood pressure (SBP), nighttime mean SBP and SBP variability (P < 0.05). Leiden score with low risk was associated with 24 h-SBP variability (r = 0.35, P = 0.006) and 24 h-diastolic blood pressure (DBP) loading (r = −0.18, P = 0.027). Leiden score with medium and high risk was associated with nighttime mean SBP (r = 0.23, P = 0.005), 24 h-SBP variability (r = 0.32, P = 0.003), and the decrease of nighttime SBP (r = 0.24, P = 0.019). Multivariate Logistic analysis showed that smoking [odds ratio (OR) = 1.014, 95% confidential interval (CI): 1.0–1.07, P = 0.03], diabetes (OR = 1.43, 95% CI: 1.10–2.26, P = 0.01) and 24 h-SBP variability (OR = 1.35, 95% CI: 1.01–2.46, P = 0.01) were independently associated with Leiden score with medium and high risk.

Conclusion

Larger SBP variability in hypertensive patients indicates the higher Leiden score and consequently the more serious coronary atherosclerotic plaque. Monitoring SBP variability has certain significance for predicting the severity of coronary atherosclerotic plaque and preventing its progression.
From source to sea: Floating macroplastic transport along the Rhine river
Authors: Kuizenga Boaz , Tasseron Paolo F. , Wendt-Potthoff Katrin , van Emmerik Tim H. M.
Published: May 2023

Rivers are pathways and storage zones for plastic pollution. Land-based plastic waste enters river systems through anthropogenic and hydrometeorological processes, after which they are transported and retained. Only a small fraction (<2%) is assumed to make it into the ocean. Understanding and quantifying river plastic transport are important to optimize prevention and reduction strategies and to evaluate the efficacy of new regulations and interventions. To achieve this, consistent and reliable data are crucial. River plastic pollution monitoring is still an emerging field, especially since river-scale plastic pollution assessments are limited to date. Here, we present an estimate of floating plastic transport and polymer characterization along the Rhine, from Switzerland to the river mouth in Netherlands. We show plastic transport is highly variable along the river, but with a significant increase towards the river mouth. High plastic transport was observed close to urban areas, and confluences with tributaries, suggesting both are likely entry points of plastic pollution. The largest plastic transport was measured in the estuary, which is explained by the tidal dynamics, limiting the transport of plastic into the sea. Our results can be used as a baseline to compare with future assessments. Furthermore, the plastic transport and composition estimates can be directly compared to other rivers that applied the same approach, which may reduce the uncertainty in global river plastic emission simulations. With our study, we aim to contribute to the development of a simple harmonized plastic monitoring approach to quantify plastic pollution at the river basin scale.
Knowledge, attitudes, and adherence relating to COVID-19 and its prevention measures in high-risk districts of Uganda in 2020
Authors: Methodius Tubihemukama , Musewa Angella , Mirembe Bernadette Basuta , Birungi Doreen , Nitumusiima Sarah , Naigaga Irene , Kabasa John David , Bazeyo William
Published: May 2023

Introduction

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. There were no licensed vaccines or explicit medicines available for treatment at the time of conducting this study. Public health and social measures (PHSM) have been widely adopted to reduce the transmission of COVID-19. Hence, assessing people's knowledge, attitudes, and adherence/practices related to the management of COVID-19 is crucial for identifying the factors that may promote or hinder adherence to the implementation of PHSM.

Methods

We conducted a cross-sectional study in the Amuru, Kyotera, Wakiso, and Kampala districts of Uganda. We used a simple random sampling technique to select households and conducted face-to-face interviews in selected households. We administered questionnaires to respondents to assess the factors that promote or hinder adherence to and knowledge about PHSM implementation. We used a Likert scale to assess respondents’ attitudes toward COVID-19.

Results

Out of the 270 respondents, 54 (20%), 73 (27%), 42 (15.6%), and 101 (37.4%) were from the Kampala, Amuru, Wakiso, and Kyotera districts, respectively. Most of the respondents had adequate knowledge (72.2%), a high level of adherence (63.7%), and approximately 57.8% had good attitudes relating to COVID-19 and its prevention measures. An inferential analysis revealed that people from the Kampala district had higher chances (odds ratio = 4.668) of having a high level of knowledge compared to people from the Amuru district. It was also found that respondents who had a high level of (adequate) knowledge were twice as likely to have good attitudes compared to those with a low level of knowledge. In addition, people with good attitudes were 2.5 times as likely to adhere to the COVID-19 prevention measures compared to those with poor attitudes.

Conclusion

Most respondents had limited knowledge though the majority of them had adopted practices to prevent the spread of COVID-19. Respondents with low knowledge of COVID-19 need to be targeted, to improve their attitude toward the disease and their adherence to safe prevention practices.
Application of microbial membrane tetraether lipids in speleothems
Authors: Zang Jingjie , Yang Huan , Zhang Jiahao , Tang Huiru , Tan Liangcheng
Published: May 2023

Glycerol dialkyl glycerol tetraethers (GDGTs), which are derived from microbial membranes, occur widely in soils, peats, lake sediments, marine sediments, hot springs, and other environments. GDGTs respond sensitively to environmental changes and have become an important tool in paleoenvironmental reconstruction. However, their application in speleothems, one of the most important archives of the study of past climates, has been quite limited. In this paper, we review the recent progress in the study of GDGTs in speleothems, from their sources to their distribution characteristics and paleoenvironmental applications. GDGTs in speleothems have been shown to come from dripping water, and cave systems. The distribution of GDGTs in speleothems shows that archaeal isoprenoid GDGTs (isoGDGTs) dominate over bacterial branched GDGTs (brGDGTs). The proxies based on isoGDGTs (TEX86) and brGDGTs (MBT/CBT) are correlated with temperature, which may offer promising potential methods for reconstructing terrestrial palaeotemperature. Ultimately, we discuss the difficulties and problems to be solved in studying speleothem GDGTs and the possible future directions for this field.
TLSEA: a tool for lncRNA set enrichment analysis based on multi-source heterogeneous information fusion
Authors: Li Jianwei , Li Zhiguang , Wang Yinfei , Lin Hongxin , Wu Baoqin
Published: May 2023

Long non-coding RNAs (lncRNAs) play an important regulatory role in gene transcription and post-transcriptional modification, and lncRNA regulatory dysfunction leads to a variety of complex human diseases. Hence, it might be beneficial to detect the underlying biological pathways and functional categories of genes that encode lncRNA. This can be carried out by using gene set enrichment analysis, which is a pervasive bioinformatic technique that has been widely used. However, accurately performing gene set enrichment analysis of lncRNAs remains a challenge. Most conventional enrichment analysis methods have not exhaustively included the rich association information among genes, which usually affects the regulatory functions of genes. Here, we developed a novel tool for lncRNA set enrichment analysis (TLSEA) to improve the accuracy of the gene functional enrichment analysis, which extracted the low-dimensional vectors of lncRNAs in two functional annotation networks with the graph representation learning method. A novel lncRNA–lncRNA association network was constructed by merging lncRNA-related heterogeneous information obtained from multiple sources with the different lncRNA-related similarity networks. In addition, the random walk with restart method was adopted to effectively expand the lncRNAs submitted by users according to the lncRNA–lncRNA association network of TLSEA. In addition, a case study of breast cancer was performed, which demonstrated that TLSEA could detect breast cancer more accurately than conventional tools. The TLSEA can be accessed freely at http://www.lirmed.com:5003/tlsea.
Diffuse large B-cell lymphoma microenvironment displays a predominant macrophage infiltrate marked by a strong inflammatory signature
Authors: Serna Leyre , Azcoaga Peio , Brahmachary Manisha , Caffarel Maria M. , Braza Mounia S.
Published: May 2023

Inflammasomes are cytosolic signaling hubs that promote the inflammatory response (i.e. an immune reaction to counteract threats in physiological conditions). Their potential role in lymphomagenesis remains to be elucidated. Depending on the context, innate immune cells, such as macrophages, may induce inflammation that contributes to the anti-tumor function; however, if uncontrolled, inflammation can promote cancer development. Here, we exploited bioinformatic tools, TCGA data, and tumor tissue samples from patients with diffuse large B-cell lymphoma (DLBCL), one of the most frequent non-Hodgkin lymphomas of B-cell origin, to investigate the distribution of the different immune cell subpopulations in DLBCL samples in order to characterize the immune landscape of their microenvironment. We found a clear prominence of macrophages in the DLBCL microenvironment. Particularly, the proportions of resting M0 and pro-inflammatory M1 macrophages were higher in DLBCL than spleen samples (controls). As each inflammasome has unique sensor activation and platform assembly mechanisms, we examined the expression of a large panel of inflammasome actors. We found that inflammasome components, cytokines and Toll-like receptors were upregulated in DLBCL samples, particularly in M0 and M1 macrophages, compared with controls. Moreover, their expression level was positively correlated with that of CD68 (a pan-macrophage marker). We confirmed the positive correlation between CD68 and IRF8 expression at the protein level in DLBCL tissue samples, where we observed increased infiltration of CD68- and IRF8-positive cells compared with normal lymph nodes. Altogether, our results highlight the inflammatory status of the DLBCL microenvironment orchestrated by macrophages. More work is needed to understand the complexity and potential therapeutic implications of inflammasomes in DLBCL.
The potential of regulatory T cell-based therapies for alopecia areata
Authors: Wan Sheng , Xu Wen , Xie Bo , Guan Cuiping , Song Xiuzu
Published: May 2023

Cytotoxic T lymphocyte has been a concern for the etiopathogenesis of alopecia areata (AA), some recent evidence suggests that the regulatory T (Treg) cell deficiency is also a contributing factor. In the lesional scalp of AA, Treg cells residing in the follicles are impaired, leading to dysregulated local immunity and hair follicle (HF) regeneration disorders. New strategies are emerging to modulate Treg cells’ number and function for autoimmune diseases. There is much interest to boost Treg cells in AA patients to suppress the abnormal autoimmunity of HF and stimulate hair regeneration. With few satisfactory therapeutic regimens available for AA, Treg cell-based therapies could be the way forward. Specifically, CAR-Treg cells and novel formulations of low-dose IL-2 are the alternatives.
Repurposing pentamidine for cancer immunotherapy by targeting the PD1/PD-L1 immune checkpoint
Authors: Gu Tingxuan , Tian Xueli , Wang Yuanyuan , Yang Wenqian , Li Wenwen , Song Mengqiu , Zhao Ran , Wang Mengqiao , Gao Quanli , Li Tiepeng , Zhang Chengjuan , Kundu Joydeb Kumar , Liu Kangdong , Dong Zigang , Lee Mee-Hyun
Published: May 2023

Immunotherapy has emerged as an effective therapeutic approach to several cancer types. The reinvigoration of tumor-infiltrating lymphocyte-mediated immune responses via the blockade of immune checkpoint markers, such as program cell death-1 (PD-1) or its cognate ligand PD-L1, has been the basis for developing clinically effective anticancer therapies. We identified pentamidine, an FDA-approved antimicrobial agent, as a small-molecule antagonist of PD-L1. Pentamidine enhanced T-cell-mediated cytotoxicity against various cancer cells in vitro by increasing the secretion of IFN-γ, TNF-α, perforin, and granzyme B in the culture medium. Pentamidine promoted T-cell activation by blocking the PD-1/PD-L1 interaction. In vivo administration of pentamidine attenuated the tumor growth and prolonged the survival of tumor-bearing mice in PD-L1 humanized murine tumor cell allograft models. Histological analysis of tumor tissues showed an increased number of tumor-infiltrating lymphocytes in tissues derived from pentamidine-treated mice. In summary, our study suggests that pentamidine holds the potential to be repurposed as a novel PD-L1 antagonist that may overcome the limitations of monoclonal antibody therapy and can emerge as a small molecule cancer immunotherapy.
Prognostic value of prelymphodepletion absolute lymphocyte counts in relapsed/refractory diffuse large B-cell lymphoma patients treated with chimeric antigen receptor T cells
Authors: Lu Yanyan , Zhu Hong , Liu Yang , Wang Ying , Sun Yinxiang , Cheng Hai , Yan Zhiling , Cao Jiang , Sang Wei , Zhu Feng , Li Depeng , Sun Haiying , Zheng Junnian , Xu Kailin , Li Zhenyu
Published: May 2023

Introduction

Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented efficacy recently. However, the factors related to responses and durable remission are elusive. This study was to investigate the impact of pre-lymphodepletion (pre-LD) absolute lymphocyte count (ALC) on CAR T cell therapy outcomes.

Methods

We conducted a retrospective study of 84 patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who underwent CAR T cell treatment at the Affiliated Hospital of Xuzhou Medical University between March 1,2016 and December 31, 2021. The enrolled patients were divided into high group and low group according to the optimal cutoff value of pre-LD ALC. The Kaplan-Meier analyses was used to calculate survival curves. The Cox proportional hazards model was used for univariate and multivariate analysis to assess the prognostic factors.

Results

The ROC showed that the optimal cutoff value of pre-LD ALC was 1.05 x 109/L. The overall response (defined as partial response or complete response) rate was significantly higher in patients with a high pre-LD ALC (75% versus 52.08%; P=0.032). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those having a high pre-LD ALC (median OS, 9.6 months versus 45.17 months [P=0.008]; median PFS, 4.07 months versus 45.17 months [P= 0.030]). Meanwhile, low pre-LD ALC is an independent risk factor for PFS and OS.

Discussion

The data suggested that pre-LD ALC may serve as a helpful indicator to predict the outcomes of CAR T cell therapy in patients with R/R DLBCL.
MIR222HG attenuates macrophage M2 polarization and allergic inflammation in allergic rhinitis by targeting the miR146a-5p/TRAF6/NF-κB axis
Authors: Wen Silu , Li Fen , Tang Yulei , Dong Lin , He Yan , Deng Yuqin , Tao Zezhang
Published: May 2023

Although M2 macrophages are involved in the orchestration of type 2 inflammation in allergic diseases, the mechanisms underlying non-coding RNA (ncRNA)-mediated macrophage polarization in allergic rhinitis (AR) have not been systematically understood. Here, we identified long non-coding RNA (lncRNA) MIR222HG as a key regulator of macrophage polarization and revealed its role in AR. Consistent with our bioinformatic analysis of GSE165934 dataset derived from the Gene Expression Omnibus (GEO) database, lncRNA-MIR222HG and murine mir222hg were downregulated in our clinical samples and animal models of AR, respectively. Mir222hg was upregulated in M1 macrophages and downregulated in M2 macrophages. The allergen-ovalbumin facilitated polarization of RAW264.7 cells to the M2 phenotype, accompanied by the downregulation of mir222hg expression in a dose-dependent manner. Mir222hg facilitates macrophage M1 polarization and reverses M2 polarization caused by ovalbumin. Furthermore, mir222hg attenuates macrophage M2 polarization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway. Collectively, the data highlight the remarkable role of MIR222HG in the modulation of macrophage polarization and allergic inflammation, as well as its potential role as a novel AR biomarker or therapeutic target.
The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment
Authors: Wang Man , Zhang Yuan , Li Chunmei , Chang Wenguang , Zhang Lei
Published: May 2023

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals’ susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.
A prediction model identifying glycolysis signature as therapeutic target for psoriasis
Authors: Shou Yanhong , Zhu Ronghui , Tang Zhenwei , Man Xiao-Yong
Published: May 2023

Background

The hyperproliferation featured with upregulated glycolysis is a hallmark of psoriasis. However, molecular difference of keratinocyte glycolysis amongst varied pathologic states in psoriasis remain elusive.

Objectives

To characterize glycolysis status of psoriatic skin and assess the potential of glycolysis score for therapeutic decision.

Methods

We analyzed 345414 cells collected from different cohorts of single-cell RNA seq database. A new method, Scissor, was used to integrate the phenotypes in GSE11903 to guide single-cell data analysis, allowing identification of responder subpopulations. AUCell algorithm was performed to evaluate the glycolysis status of single cell. Glycolysis signature was used for further ordering in trajectory analysis. The signature model was built with logistic regression analysis and validated using external datasets.

Results

Keratinocytes (KCs) expressing SLC2A1 and LDH1 were identified as a novel glycolysis-related subpopulation. Scissor+ cells and Scissor− cells were defined as response and non-response phenotypes. In Scissor+SLC2A1+ LDH1+ KCs, ATP synthesis pathway was activated, especially, the glycolysis pathway being intriguing. Based on the glycolysis signature, keratinocyte differentiation was decomposed into a three-phase trajectory of normal, non-lesional, and lesional psoriatic cells. The area under the curve (AUC) and Brier score (BS) were used to estimate the performance of the glycolysis signature in distinguishing response and non-response samples in GSE69967 (AUC =0.786, BS =17.7) and GSE85034 (AUC=0.849, BS=11.1). Furthermore, Decision Curve Analysis suggested that the glycolysis score was clinically practicable.

Conclusion

We demonstrated a novel glycolysis-related subpopulation of KCs, identified 12-glycolysis signature, and validated its promising predictive efficacy of treatment effectiveness.
Phytoplankton dynamics in nearshore regions of the western Antarctic Peninsula in relation to a variable frontal zone in the Gerlache Strait
Authors: Mascioni Martina , Almandoz Gastón O. , Cusick Allison , Pan B. Jack , Vernet Maria
Published: May 2023

The Gerlache Strait is a narrow channel that separates the western coast of the Antarctic Peninsula (WAP) from the Palmer Archipelago. This area is characterized by the presence of interconnected fjords, bays, islands, and channels that serve as a refuge for megafauna during summer. Through the framework of FjordPhyto – a citizen science collaboration with the International Association of Antarctica Tour Operators (IAATO) vessels – we assessed phytoplankton biomass and composition in surface waters of six under-explored nearshore areas connected to the Gerlache Strait (between 64° and 65° S) during three consecutive seasons, from November to March (2016–2019). During the first two seasons, we found significant differences in the phytoplankton community distribution and successional patterns to the north and south of the sampling area; the greatest differences were evidenced mainly in the months of high biomass, December and January. During December, cryptophytes bloomed in the north, while microplanktonic diatoms dominated in the south, and during January, small centric diatoms dominated in the north, while prasinophytes bloomed in the south. This spatial distinction in phytoplankton communities were mainly associated with the occurrence of a surface thermal front in the Gerlache Strait around 64.5° S. The presence of the front separating warm waters to the north and colder waters to the south, during the months of December to February, was confirmed by the analysis of 10 years of remote sensing data. By contrast, during the third season, low biomass prevailed, and no differences in the phytoplankton composition between the north and south areas were observed. The third season was the coldest of the series, with smaller differences in water temperature north and south of the usual front location. This study shows for the first time a complete overview of the phytoplankton composition throughout the entire growth season (November through March) in the nearshore areas of the WAP between 64° and 65° S. The results of this work contribute to the understanding of the phytoplankton community in relation to small scale physical features during the Antarctic austral summer.
Ecotrophic perspective in fisheries management: a review of Ecopath with Ecosim models in European marine ecosystems
Authors: Keramidas Ioannis , Dimarchopoulou Donna , Ofir Eyal , Scotti Marco , Tsikliras Athanassios C. , Gal Gideon
Published: May 2023

The aim of this work is to present the food web models developed using the Ecopath with Ecosim (EwE) software tool to describe structure and functioning of various European marine ecosystems (eastern, central and western Mediterranean Sea; Black Sea; Bay of Biscay, Celtic Sea and Iberian coast; Baltic Sea; North Sea; English Channel, Irish Sea and west Scottish Sea; and Norwegian and Barents Seas). A total of 195 Ecopath models based on 168 scientific publications, which report original, updated and modified versions, were reviewed. Seventy models included Ecosim temporal simulations while 28 implemented Ecospace spatiotemporal dynamics. Most of the models and publications referred to the western Mediterranean Sea followed by the English Channel, Irish Sea and west Scottish Sea sub-regions. In the Mediterranean Sea, the western region had the largest number of models and publications, followed by the central and eastern regions; similar trends were observed in previous literature reviews. Most models addressed ecosystem functioning and fisheries-related hypotheses while several investigated the impact of climate change, the presence of alien species, aquaculture, chemical pollution, infrastructure, and energy production. Model complexity (i.e., number of functional groups) increased over time. Main forcing factors considered to run spatial and temporal simulations were trophic interactions, fishery, and primary production. Average scores of ecosystem indicators derived from the Ecopath summary statistics were compared. Uncertainty was also investigated based on the use of the Ecosampler plug-in and the Monte Carlo routine; only one third of the reviewed publications incorporated uncertainty analysis. Only a limited number of the models included the use of the ECOIND plug-in which provides the user with quantitative output of ecological indicators. We assert that the EwE modelling approach is a successful tool which provides a quantitative framework to analyse the structure and dynamics of ecosystems, and to evaluate the potential impacts of different management scenarios.
Postoperative short-term mortality between insulin-treated and non-insulin-treated patients with diabetes after non-cardiac surgery: a systematic review and meta-analysis
Authors: Jiang Jie , Wang Shuo , Sun Rao , Zhao Yilin , Zhou Zhiqiang , Bi Jiangjiang , Luo Ailin , Li Shiyong
Published: May 2023

Background

Diabetes mellitus is an independent risk factor for postoperative complications. It has been reported that insulin-treated diabetes is associated with increased postoperative mortality compared to non-insulin-treated diabetes after cardiac surgery; however, it is unclear whether this finding is applicable to non-cardiac surgery.

Objective

We aimed to assess the effects of insulin-treated and non-insulin-treated diabetes on short-term mortality after non-cardiac surgery.

Methods

Our study was a systematic review and meta-analysis of observational studies. PubMed, CENTRAL, EMBASE, and ISI Web of Science databases were searched from inception to February 22, 2021. Cohort or case-control studies that provided information on postoperative short-term mortality in insulin-treated diabetic and non-insulin-treated diabetic patients were included. We pooled the data with a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to rate the quality of evidence.

Results

Twenty-two cohort studies involving 208,214 participants were included. Our study suggested that insulin-treated diabetic patients was associated with a higher risk of 30-day mortality than non-insulin-treated diabetic patients [19 studies with 197,704 patients, risk ratio (RR) 1.305; 95% confidence interval (CI), 1.127 to 1.511; p < 0.001]. The studies were rated as very low quality. The new pooled result only slightly changed after seven simulated missing studies were added using the trim-and-fill method (RR, 1.260; 95% CI, 1.076–1.476; p = 0.004). Our results also showed no significant difference between insulin-treated diabetes and non-insulin-treated diabetes regarding in-hospital mortality (two studies with 9,032 patients, RR, 0.970; 95% CI, 0.584–1.611; p = 0.905).

Conclusion

Very-low-quality evidence suggests that insulin-treated diabetes was associated with increased 30-day mortality after non-cardiac surgery. However, this finding is non-definitive because of the influence of confounding factors.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246752, identifier: CRD42021246752.
Maggot extracts chemo-prevent inflammation and tumorigenesis accompanied by changes in the intestinal microbiome and metabolome in AOM/DSS-induced mice
Authors: Tang Xun , Wang Lei , Wang Daojuan , Zhang Yi , Wang Tingyu , Zhu Zhengquan , Weng Yajing , Tao Gaojian , Wang Qin , Tang Li , Yan Feng , Wang Yong
Published: May 2023

Inflammatory responses and intestinal microbiome play a crucial role in the progression of colitis-associated carcinoma (CAC). The traditional Chinese medicine maggot has been widely known owing to its clinical application and anti-inflammatory function. In this study, we investigated the preventive effects of maggot extract (ME) by intragastric administration prior to azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC in mice. The results showed that ME had superior advantages in ameliorating disease activity index score and inflammatory phenotype, in comparison with the AOM/DSS group. The number and size of polypoid colonic tumors were decreased after pre-administration of ME. In addition, ME was found to reverse the downregulation of tight junction proteins (zonula occluden-1 and occluding) while suppressing the levels of inflammatory factors (IL-1β and IL-6) in models. Moreover, Toll-like receptor 4 (TLR4) mediated intracellular nuclear factor-κB (NF-κB)-containing signaling cascades, including inducible nitric oxide synthase and cyclooxygenase-2, and exhibited decreasing expression in the mice model after ME pre-administration. 16s rRNA analysis and untargeted-metabolomics profiling of fecal samples inferred that ME revealed ideal prevention of intestinal dysbiosis in CAC mice, accompanied by and correlated with alterations in the composition of metabolites. Overall, ME pre-administration might be a chemo-preventive candidate in the initiation and development of CAC.
Interactions of the protein tyrosine phosphatase PTPN3 with viral and cellular partners through its PDZ domain: insights into structural determinants and phosphatase activity
Authors: Genera Mariano , Colcombet-Cazenave Baptiste , Croitoru Anastasia , Raynal Bertrand , Mechaly Ariel , Caillet Joël , Haouz Ahmed , Wolff Nicolas , Caillet-Saguy Célia
Published: May 2023

The human protein tyrosine phosphatase non-receptor type 3 (PTPN3) is a phosphatase containing a PDZ (PSD-95/Dlg/ZO-1) domain that has been found to play both tumor-suppressive and tumor-promoting roles in various cancers, despite limited knowledge of its cellular partners and signaling functions. Notably, the high-risk genital human papillomavirus (HPV) types 16 and 18 and the hepatitis B virus (HBV) target the PDZ domain of PTPN3 through PDZ-binding motifs (PBMs) in their E6 and HBc proteins respectively. This study focuses on the interactions between the PTPN3 PDZ domain (PTPN3-PDZ) and PBMs of viral and cellular protein partners. We solved the X-ray structures of complexes between PTPN3-PDZ and PBMs of E6 of HPV18 and the tumor necrosis factor-alpha converting enzyme (TACE). We provide new insights into key structural determinants of PBM recognition by PTPN3 by screening the selectivity of PTPN3-PDZ recognition of PBMs, and by comparing the PDZome binding profiles of PTPN3-recognized PBMs and the interactome of PTPN3-PDZ. The PDZ domain of PTPN3 was known to auto-inhibit the protein’s phosphatase activity. We discovered that the linker connecting the PDZ and phosphatase domains is involved in this inhibition, and that the binding of PBMs does not impact this catalytic regulation. Overall, the study sheds light on the interactions and structural determinants of PTPN3 with its cellular and viral partners, as well as on the inhibitory role of its PDZ domain on its phosphatase activity.
Involvement of baroreflex deficiency in the age-related loss of estrogen efficacy against cerebral ischemia
Authors: Wang Lei , Wang Jia , Shan Qing , Shu He , Guo Jin-Min
Published: May 2023

For post-menopausal women, stroke is complicated by the variable effects of estrogen therapy and the age-related therapeutic consequences involved. Estrogen therapy has been shown to have an age-dimorphic effect, which is neuroprotective in young females, but non-neuroprotective, even neurotoxic in acyclic females. We hypothesized that arterial baroreflex (ABR) and its downstream acetylcholine-α7 nicotinic acetylcholine receptor (α7nAChR) anti-inflammatory pathways are involved in estrogen efficacy toward cerebral ischemic damage. Our data showed that estrogen supplements contributed to ABR improvement and neuroprotection in adult, not aged, ovariectomized (OVX) rats. In adult rats, OVX-induced estrogen deficiency aggravated middle cerebral artery occlusion (MCAO), which induced brain infarction and reduced ABR function, with decreased α7nAChR expression of the brain and exaggerated inflammation following MCAO; these effects were significantly prevented by supplementation with estrogen. ABR impairment by sinoaortic denervation partly attenuated the estrogen effect on baroreflex sensitivity (BRS) and ischemic damage in adult rats, as well as α7nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-α7nAChR anti-inflammatory pathways are involved in the neuroprotection of estrogen in adult OVX rats. In contrast, aged rats exhibited more severe ischemic damage and inflammatory response than adult rats, as well as poorer baroreflex function and lower α7nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain α7nAChR and post-ischemic inflammation. Most importantly, ketanserin restored ABR function and significantly postponed the onset of stroke in aged female strokeprone spontaneously hypertensive rats, whereas estrogen treatment failed to delay the development of stroke. Our findings reveal that estrogen is protective against ischemic stroke (IS) in adult female rats and that ABR played a role in this beneficial action. Dysfunction of ABR and unresponsiveness to estrogen in aged female rats may contribute to a reduced estrogen efficacy against cerebral ischemia.
The efficacy and safety of gabapentin vs. carbamazepine in patients with primary trigeminal neuralgia: A systematic review and meta-analysis
Authors: Zhao Xin , Ge Shuyu
Published: May 2023

Background

Drug therapy is the most commonly used treatment for primary trigeminal neuralgia (PTN), in which carbamazepine is the first-line drug. Recently, the anti-epileptic drug gabapentin has also been widely used in patients with PTN, but whether it can be used as a substitute for carbamazepine still needs to be verified. Our study aimed to assess the safety and efficacy of gabapentin vs. carbamazepine as a treatment for PTN.

Methods

We searched seven electronic databases for studies published as of 31 July 2022. All randomized controlled trials (RCTs) of gabapentin vs. carbamazepine on patients with PTN that met the inclusion criteria were included. Meta-analysis was conducted using Revman 5.4 and Stata 14.0, in which forest plots, funnel plots, and sensitivity analysis were performed. Mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were used for the measurement indicators of continuous and categorical variables, respectively.

Results

A total of 18 RCTs with 1,604 patients were eventually identified. The meta-analysis showed that compared with the carbamazepine group, the gabapentin group significantly improved the effective rate (OR = 2.02, 95% CI 1.56 to 2.62, P < 0.001), reduced the adverse event rate (OR = 0.28, 95% CI 0.21 to 0.37, P < 0.001), and improved the visual analog scale (VAS) score (MD = −0.46, 95% CI −0.86 to −0.06, P = 0.03). Although the funnel plot showed evidence of publication bias, the sensitivity analysis revealed the stability of the results.

Conclusion

The current evidence showed that gabapentin may be superior to carbamazepine in relation to efficacy and safety in patients with PTN. It is crucial that more RCTs are conducted to confirm the conclusion in the future.
Is aspiration an effective acute stroke treatment in older adults?
Authors: Narloch Jerzy , Piasecki Adam , Ziecina Piotr , Dȩbiec Aleksander , Wierzbicki Marek , Staszewski Jacek , Piasecki Piotr
Published: May 2023

Introduction

Clinical outcomes after interventional stroke treatment rely on several factors, with older age being associated with poorer results, which are mainly attributed to patient's comorbidities and medications. The delivery of an aspiration catheter could be hindered by carotid tortuosity, which is more prevalent in elderly patients with increasing age. In this study, we aimed to compare the clinical and angiographic outcomes of a direct aspiration first-pass technique in interventional stroke treatment for elderly patients compared with younger patients.

Materials and methods

A total of 162 patients (92 women and 70 men, aged between 35 and 94 years +/– 12.4 years) were included in this study. Patients who were treated in a comprehensive stroke center due to a large-vessel occlusion stroke using aspiration as the first-choice treatment were included in this study. To evaluate carotid arteries, the tortuosity index (TI) was calculated for each segment of each carotid pathway.

Results

Age correlated significantly with the presence of carotid tortuosity (R = 0.408, p = 0.000), extracranial length ratio (R = 0.487, p = 0.000), and overall length ratio (R = 0.467, p = 0.000). No significant associations were found with coiling, kinking, or intracranial length ratio. Successful aspiration-based recanalization rate decreased with increasing age, and the differences between the age subgroups were not statistically significant. A comparison of the extreme subgroups, i.e., <60 years old vs. ≥80 years old, did not yield a statistically significant change (p = 0.068).

Conclusion

Successful aspiration-based recanalization rate decreased with increasing age; however, these differences were not significant. Clinical outcomes did not significantly differ with regard to carotid tortuosity, regardless of the time of assessment. Neither intracranial nor extracranial tortuosity was significantly associated with reperfusion-related complications in either of the age subgroups.
Effects of retinoic acid receptor α modulators on developmental ethanol-induced neurodegeneration and neuroinflammation
Authors: Saito Mariko , Subbanna Shivakumar , Zhang Xiuli , Canals-Baker Stefanie , Smiley John F. , Wilson Donald A. , Das Bhaskar C.
Published: May 2023

Ethanol exposure in neonatal mice induces acute neurodegeneration followed by long-lasting glial activation and GABAergic cell deficits along with behavioral abnormalities, providing a third trimester model of fetal alcohol spectrum disorders (FASD). Retinoic acid (RA), the active form of vitamin A, regulates transcription of RA-responsive genes and plays essential roles in the development of embryos and their CNS. Ethanol has been shown to disturb RA metabolism and signaling in the developing brain, which may be a cause of ethanol toxicity leading to FASD. Using an agonist and an antagonist specific to RA receptor α (RARα), we studied how RA/RARα signaling affects acute and long-lasting neurodegeneration and activation of phagocytic cells and astrocytes caused by ethanol administered to neonatal mice. We found that an RARα antagonist (BT382) administered 30 min before ethanol injection into postnatal day 7 (P7) mice partially blocked acute neurodegeneration as well as elevation of CD68-positive phagocytic cells in the same brain area. While an RARα agonist (BT75) did not affect acute neurodegeneration, BT75 given either before or after ethanol administration ameliorated long-lasting astrocyte activation and GABAergic cell deficits in certain brain regions. Our studies using Nkx2.1-Cre;Ai9 mice, in which major GABAergic neurons and their progenitors in the cortex and the hippocampus are labeled with constitutively expressed tdTomato fluorescent protein, indicate that the long-lasting GABAergic cell deficits are mainly caused by P7 ethanol-induced initial neurodegeneration. However, the partial reduction of prolonged GABAergic cell deficits and glial activation by post-ethanol BT75 treatment suggests that, in addition to the initial cell death, there may be delayed cell death or disturbed development of GABAergic cells, which is partially rescued by BT75. Since RARα agonists including BT75 have been shown to exert anti-inflammatory effects, BT75 may rescue GABAergic cell deficits by reducing glial activation/neuroinflammation.