bluuebunny/crossref_metadata_2025 huggingface dataset:
Forecast of total rural energy demand based on energy consumption intensity
Authors: Guilian Wu , Linyao Zhang , Tingting Lin , Hao Chen , Wenlong Li , Shaofang Wang , Jun Yan , Conghao Liu
Published: January 2023

It is necessary to build a simulation calculation model that is more in line with the actual rural energy endowment and development needs. Prediction and analysis of the total rural energy demand in the context of energy transition. The rural energy demand is affected by many factors, and the traditional single model contains very limited amount of information, which easily leads to a large deviation between the prediction results and the actual situation, thereby reducing the prediction accuracy. In view of this, in view of the complex and difficult to predict the influencing factors of rural energy demand under the new economic normal, based on the back propagation neural network-particle swarm-genetic hybrid optimization algorithm, a total rural energy demand forecast based on energy consumption intensity was constructed method. Firstly, select the key influencing factors of the total rural energy demand forecast and conduct path analysis to compare the explanation strength of the influencing factors on energy demand; secondly, construct the energy consumption demand regression model, and calculate the parameters based on the back propagation neural network-particle swarm-genetic hybrid optimization algorithm. Estimation results; finally, the scenario is given, and the regional rural energy demand forecast results are obtained by using the regression model. Empirical analysis shows that four aspects of GDP, industrial structure, energy utilization efficiency, and rural energy consumption are strongly correlated with the total rural energy demand. At the same time, the prediction error of this study can reach about 1.35%, which can predict future rural energy demand. The total amount to guide the construction of the rural energy system.
Phase-field simulation of grain nucleation, growth, and Rayleigh distribution of U3Si2 nuclear fuel
Authors: Ma Cong , Zhao Min , Xin Tianyuan , Wu Lu , Pan Rongjian , Qin Jiantao , Zhang Jing
Published: January 2023

U3Si2 is a potential accident-tolerant fuel (ATF) due to its high thermal conductivity and uranium density relative to UO2. The grain size and distribution play an essential role in the service performance of U3Si2. However, the grain evolution is quite complicated and remains unclear, which limits further application of U3Si2 in the ATF assembly. In the present work, a phase-field model is employed to investigate the nucleation and growth of grains in U3Si2. Our results show that the number of grains rises rapidly at the nucleation stage until they occupy the whole system. After that, the grain radius and area continue to grow, and the grain number decays. The grain area increases in time according to the linear law, while the mean grain radius increases with time in a power law form with the scaling growth exponent z = 0.42, which is quite close to the theoretically predicted value. Finally, we performed statistical analysis and found that the grain size evolution of U3Si2 obeys Rayleigh distribution. Our simulation not only elucidates the nucleation and evolution of grains in U3Si2 during the thermal treatment process unambiguously but also provides a fundamental study on the investigation of grain growth, subdivision, and even amorphization in the irradiated condition, which is very important for U3Si2 used as ATF in the light water reactor.
Carbonaceous electrode materials for supercapacitor: Preparation and surface functionalization
Authors: Lv Yaokang , Wang Juncheng , Ji Dingwei , Li Jianhang , Zhao Suaisuai , Zhao Yingjian , Cai Zhiwei , He Xuehua , Sun Xiaofang
Published: January 2023

Supercapacitors became more and more important recently in the area of energy storage and conversion. Their large power deliveries abilities, high stability and environmental friendliness characteristics draw tremendous attention in high-power applications such as public transit networks. Carbonaceous materials with unique surface and electrochemical properties were widely used in supercapacitors as electrode materials. This review focuses on the developments in supercapacitor electrodes made from carbonaceous materials recently, their working principle and evaluation parameters were summarized briefly. The preparation methods and electrochemical properties of different carbonaceous materials were compared and classified. It was found that the surface situation (e.g., porous structure, hydrophilic) of carbonaceous materials strongly affect the electrochemical performances of supercapacitor. So far, active carbons would be the most applicable carbonaceous electrode materials owing to their good chemical stability and conductivity, extensive accessibility inexpensiveness. But their energy densities still fall behind practical demands. Both theoretical calculations and experimental studies show that surface modification and doping of carbonaceous materials can not only optimize their pore size, structure, conductivity and surface properties, but also can introduce extra pseudocapacitance into these materials. Considering global environmental pollution and energy shortage problems nowadays, we sincerely suggested that future work should focus on domestic, medical and industrial wastes residues derived carbonaceous materials and scaled production process such as reactors and exhaust gas treatment.
An isolated chemolithoautotrophic ecosystem deduced from environmental isotopes: Ayyalon cave (Israel)
Authors: Frumkin Amos , Chipman Ariel D. , Naaman Israel
Published: January 2023

The stable isotopes composition of chemolithoautotrophic cave ecosystems is known to differ from epigenic caves. Here we show that in addition, dead carbon (devoid of 14C), is utilized and transferred throughout this ecosystem, rendering it unsuitable for radiocarbon dating. The connectivity of the Ayyalon Cave ecosystem with the surface is studied, along with its sources of energy and carbon, as well as the interconnections between its constituents. We use isotopic evidence to show that its ancient resilient ecosystem is based on an underground food web depending on rich biomass production by chemolithoautotrophic nutrient supplies, detached from surface photosynthesis. Carbon isotopic values indicate that: (1) the microbial biota use bicarbonate from the groundwater (23.34 pMC [% of modern carbon]) rather than the atmospheric CO2 above the water (71.36 pMC); (2) the depleted 14C signal is transferred through the entire ecosystem, indicating that the ecosystem is well-adapted and based on the cave biofilm which is in turn based on groundwater-dissolved inorganic carbon. Incubation of Ayyalon biofilm with 14C-labelled bicarbonate indicates uptake of the radio-labeled bicarbonate by sulfur-oxidizing proteobacteria Beggiatoa, suggesting that these sulfur-oxidizing microorganisms use the water-dissolved inorganic carbon for chemolithoautotrophic carbon fixation. Organic matter in the cave is much lighter in its stable nitrogen and carbon isotopes compared with respective surface values, as expected in chemolithoautotrophic systems. This evidence may be applicative to subsurface voids of ancient Earth environments and extraterrestrial systems.
Remote sensing methods for estimating tree species of forests in the Volyn region, Ukraine
Authors: Melnyk Oleksandr , Manko Pavlo , Brunn Ansgar
Published: January 2023

Forest classification is needed to solve a wide range of environmental issues related to of forest classes and succession processes, the extent of afforestation and deforestation and global environmental change. These applications require a very accurate mapping and monitoring of forest types. This article investigates the combination of modern open geographic information systems and remote sensing data in forest management tasks for a specific part of the Ukrainian state area. Based on the existing afforestation plans, the results of the unsupervised classification of Sentinel-2 images and the selection of forest species fragments with closed crowns as training data for supervised classification, classifiers of forest species of the study object were developed with and without taking into account age groups. A supervised classification of research objects is realized and the accuracy of the obtained results is evaluated. It is established that the accuracy of determining forest species on the basis of the proposed method is 90.3 and 91.4%, taking into account age groups and without taking them into account, respectively. Thus, it is found that the modeling of the age groups does not improve the classification result for the test area.
Identification of platinum resistance-related gene signature for prognosis and immune analysis in bladder cancer
Authors: Li Sheng , Jiang Ming , Yang Lin , Zheng Fucun , Liu Jiahao , Situ Xiong , Liu Xiaoqiang , Weipeng Liu , Fu Bin
Published: January 2023

Purpose: Currently, there is limited knowledge about platinum resistance-related long non-coding RNAs (lncRNAs) in bladder cancer. We aim to identify platinum resistance-related lncRNAs and construct a risk model for accurate prognostic prediction of bladder cancer.

Methods: Transcriptomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) database, and platinum resistance-related genes were obtained from HGSOC-Platinum. The platinum resistance-related lncRNAs were obtained by the Spearman correlation analysis. Then, we constructed a risk score model through Cox regression analysis and the LASSO algorithm. The model was verified by analyzing the median risk score, Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and heatmap. We also developed a nomogram and examined the relationship between the risk score model, immune landscape, and drug sensitivity. Lastly, we assessed the differential expression of PRR-lncRNAs in the cisplatin-resistant bladder cancer cell line and the normal bladder cancer cell line using qRT-PCR.

Results: We developed and validated an eight-platinum resistance-related lncRNA risk model for bladder cancer. The risk model showed independent prognostic significance in univariate and multivariate Cox analyses. Based on multivariate analysis, we developed a nomogram. The modified model is both good predictive and clinically relevant after evaluation. Furthermore, immune-related and drug-sensitivity analyses also showed significant differential expression between high and low-risk groups. The qRT-PCR demonstrated that most of the lncRNAs were upregulated in cisplatin-resistance cancerous tissues than in control tissues.

Conclusion: We have developed a predictive model based on eight platinum resistance-related lncRNAs, which could add meaningful information to clinical decision-making.
Edible landscape: Key factors determining consumers’ commitment and willingness to accept opportunity cost and risk of foraged food
Authors: Rombach Meike , Dean David
Published: January 2023

Introduction

This study is dedicated to urban foraging and explores key factors that determine consumer willingness to try foraged food, willingness to spend time and effort, accept risk as well as make a commitment towards food foraging.

Methods

A conceptual model is presented where general perceptions of nature, food foraging, and Covid-19 influence 3 specific attitudes about food foraging which drive 4 behavioural intentions towards food foraging. The model was tested using partial least square structural equation modelling.

Results

Results emphasize that the strongest driver of willingness to try are the approval of responsible food foraging activities and the individual benefits of food foraging. For the willingness to spend extra time and effort, all the predictors have some impact. In terms of willingness to accept risk, approval of responsible food foraging activities and the societal benefits of food foraging are influential. For commitment to food foraging, the individual and societal benefits are the most important key drivers.

Discussion

These findings are of relevance to marketing managers in the food industry and gastronomy, as well as municipalities, landscape designers, and horticultural businesses.
Inhibition of specific signaling pathways rather than epigenetic silencing of effector genes is the leading mechanism of innate tolerance
Authors: Masyutina Anna M. , Maximchik Polina V. , Chkadua Georgy Z. , Pashenkov Mikhail V.
Published: January 2023

Introduction

Macrophages activated through a pattern-recognition receptor (PRR) enter a transient state of tolerance characterized by diminished responsiveness to restimulation of the same receptor. Signaling-based and epigenetic mechanisms are invoked to explain this innate tolerance. However, these two groups of mechanisms should result in different outcomes. The epigenetic scenario (silencing of effector genes) predicts that activation of a PRR should broadly cross-tolerize to agonists of unrelated PRRs, whereas in the signaling-based scenario (inhibition of signaling pathways downstream of specific PRRs), cross-tolerization should occur only between agonists utilizing the same PRR and/or signaling pathway. Also, the so-called non-tolerizeable genes have been described, which acquire distinct epigenetic marks and increased responsiveness to rechallenge with the same agonist. The existence of such genes is well explained by epigenetic mechanisms but difficult to explain solely by signaling mechanisms.

Methods

To evaluate contribution of signaling and epigenetic mechanisms to innate tolerance, we tolerized human macrophages with agonists of TLR4 or NOD1 receptors, which signal via distinct pathways, and assessed responses of tolerized cells to homologous restimulation and to cross-stimulation using different signaling, metabolic and transcriptomic read-outs. We developed a transcriptomics-based approach to distinguish responses to secondary stimulation from continuing responses to primary stimulation.

Results

We found that macrophages tolerized with a NOD1 agonist lack responses to homologous restimulation, whereas LPS-tolerized macrophages partially retain the ability to activate NF-κB pathway upon LPS rechallenge, which allows to sustain low-level expression of a subset of pro-inflammatory genes. Contributing to LPS tolerance is blockade of signaling pathways required for IFN-β production, resulting in ‘pseudo-tolerization’ of IFN-regulated genes. Many genes in NOD1- or TLR4-tolerized macrophages are upregulated as the result of primary stimulation (due to continuing transcription and/or high mRNA stability), but do not respond to homologous restimulation. Hyperresponsiveness of genes to homologous rechallenge is a rare and inconsistent phenomenon. However, most genes that have become unresponsive to homologous stimuli show unchanged or elevated responses to agonists of PRRs signaling via distinct pathways.

Discussion

Thus, inhibition of specific signaling pathways rather than epigenetic silencing is the dominant mechanism of innate tolerance.
Case report: Autoimmune encephalitis associated with anti-CASPR2 antibody mimicking cerebral infarction
Authors: Chen Ziqi , Tang Jing
Published: January 2023

Autoimmune encephalitis associated with antibody against contactin-associated protein-like 2 (CASPR2) varies in its clinical presentation. The disease is difficult to distinguish from some other conditions without testing for anti-CASPR2 antibody in blood serum or cerebrospinal fluid. Cerebral lesions are typically detected by magnetic resonance imaging (MRI) in the medial temporal lobe or hippocampus. Here, we describe a patient with anti-CASPR2 antibody autoimmune encephalitis whose imaging manifestations mimicked infarction in the left frontal lobe. The 48-year-old man reported memory loss, convulsions, and disturbed consciousness one day after drinking wine. The right upper arm showed reduced autonomous movement after painful stimuli, and MRI showed abnormal hyperintensities in the left frontal lobe on T2 and fluid-attenuated inversion recovery sequences, restricted diffusion, and decreased cerebral blood flow, mimicking acute cerebral infarction. Contrast-enhanced T1-weighted MRI showed gyral enhancement involving the cortex and subcortical white matter. Computed tomography angiography did not identify culprit blood vessels. Symptoms did not improve with anti-platelet or lipid-lowering therapy. Screening for serum antibodies associated with autoimmune encephalitis detected antibody against CASPR2, and intravenous immunoglobulin therapy substantially improved symptoms. This case provides the first indication that anti-CASPR2 antibody-associated autoimmune encephalitis can manifest as involvement of the cortex and subcortical white matter in the frontal lobe based on MRI. It emphasizes the need for thorough investigation, including analysis of potential autoimmunity, of patients whose imaging findings mimic ischemic infarction.
DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis
Authors: Wu Yangping , Li Wenting , Chen Xiangzheng , Wang Haichuan , Su Siyuan , Xu Ying , Deng Xiangbing , Yang Tinghan , Wei Mingtian , Li Li , Liu Yixin , Yang Jinliang , Li Weimin
Published: January 2023

Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis. The DOG1 expression profile was determined among TCGA samples and tissue microarrays. High levels of DOG1 expression were ubiquitously observed in multiple cancer samples from the alimentary tract determined by TCGA samples and tissue microarrays. Circulating tumor cells isolated from metastatic colon cancer patients were also positive for DOG1 expression. The mechanisms of anti-DOG1 antibody were investigated by dual-luciferase reporter assay. The anti-DOG1 antibody could inhibit proliferation and metastasis via p53 signaling in limited cancer cell lines. The anti-DOG1 antibody was conjugated with a microtubule inhibitor DM4, to construct a new anti-DOG1-DM4-ADC to strengthen its activity. The anti-DOG1-DM4-ADC showed cytotoxicity at the nanomolar level in vitro. In the murine xenograft tumor models, treatment of anti-DOG1-DM4-ADC achieved a significant tumor growth inhibition rate. Our study indicates that anti-DOG1-DM4-ADC may be promising therapeutic molecules for DOG1-positive alimentary tract tumors and may be effective in inhibiting recurrence after curative resection of liver metastases of colorectal origin.
Unequal distribution of genetically-intact HIV-1 proviruses in cells expressing the immune checkpoint markers PD-1 and/or CTLA-4
Authors: Fisher Katie , Schlub Timothy E. , Boyer Zoe , Rasmussen Thomas A. , Rhodes Ajantha , Hoh Rebecca , Hecht Frederick M. , Deeks Steven G. , Lewin Sharon R. , Palmer Sarah
Published: January 2023

Introduction

HIV-1 persists in resting CD4+ T-cells despite antiretroviral therapy (ART). Determining the cell surface markers that enrich for genetically-intact HIV-1 genomes is vital in developing targeted curative strategies. Previous studies have found that HIV-1 proviral DNA is enriched in CD4+ T-cells expressing the immune checkpoint markers programmed cell death protein-1 (PD-1) or cytotoxic T-lymphocyte associated protein-4 (CTLA-4). There has also been some success in blocking these markers in an effort to reverse HIV-1 latency. However, it remains unclear whether cells expressing PD-1 and/or CTLA-4 are enriched for genetically-intact, and potentially replication-competent, HIV-1 genomes.

Methods

We obtained peripheral blood from 16 HIV-1-infected participants, and paired lymph node from four of these participants, during effective ART. Memory CD4+ T-cells from either site were sorted into four populations: PD-1-CTLA-4- (double negative, DN), PD-1+CTLA-4- (PD-1+), PD-1-CTLA-4+ (CTLA-4+) and PD-1+CTLA-4+ (double positive, DP). We performed an exploratory study using the full-length individual proviral sequencing (FLIPS) assay to identify genetically-intact and defective genomes from each subset, as well as HIV-1 genomes with specific intact open reading frames (ORFs).

Results and Discussion

In peripheral blood, we observed that proviruses found within PD-1+ cells are more likely to have intact ORFs for genes such as tat, rev and nef compared to DN, CTLA-4+ and DP cells, all of which may contribute to HIV-1 persistence. Conversely, we observed that CTLA-4 expression is a marker for cells harbouring HIV-1 provirus that is more likely to be defective, containing low levels of these intact ORFs. In the lymph node, we found evidence that CTLA-4+ cells contain lower levels of HIV-1 provirus compared to the other cell subsets. Importantly, however, we observed significant participant variation in the enrichment of HIV-1 proviruses with intact genomes or specific intact ORFs across these memory CD4+ T-cell subsets, and therefore consideration of additional cellular markers will likely be needed to consistently identify cells harbouring latent, and potentially replication-competent, HIV-1.
Causal association between inflammatory bowel disease and hidradenitis suppurativa: A two-sample bidirectional Mendelian randomization study
Authors: Bao Bingzhou , Zhu Chao , Shi Jian , Lu Canxing
Published: January 2023

Background

Epidemiological studies have revealed a link between inflammatory bowel disease (IBD) and hidradenitis suppurativa (HS). To determine whether IBD and HS are causally related, we used the Mendelian randomization (MR) approach.

Methods

A two-sample MR was performed using an analysis of 12,882 patients and 21,770 controls with IBD and its main subtypes, ulcerative colitis (UC) and Crohn’s disease (CD). A total of 409 cases and 211,139 controls without hidradenitis suppurativa (HS) were included in the data for this condition from various GWAS investigations. Odds ratios (ORs) with 95% confidence intervals (CIs) are used to estimate causal effects.

Results

The study assessed the causal relationship between HS and IBD in both directions. The risk of HS was increased by IBD (IVW OR = 1.34, 95% CI = 1.20-1.49, p = 2.15E-07) and, in addition, HS was affected by UC (IVW OR = 1.27, 95% CI = 1.13-1.43, p = 8.97E-04) and CD (IVW OR = 1.18, 95% CI = 1.08-1.29, p = 4.15E-04). However, there was no evidence of a causal relationship between HS and IBD or its subtypes (IBD IVW OR = 1.00, 95% CI = 0.96-1.05, p = 0.85; UC IVW OR = 0.99, 95% CI = 0.95-1.03, p = 0.65; CD IVW OR = 1.03, 95% CI = 0.98- 1.07, p = 0.28).

Conclusion

This study demonstrates that IBD and its subtypes have a causal effect on HS, whereas HS does not affect IBD. Gut-skin axis interactions may help to understand this association. Nevertheless, further studies are needed to clarify the pathophysiology of the causal relationship between IBD and HS.
T cells and their products in diabetic kidney disease
Authors: Liu Yue , Lv Yaodong , Zhang Tingwei , Huang Tongtong , Lang Yating , Sheng Qinghao , Liu Yingxiao , Kong Zhijuan , Gao Ying , Lu Shangwei , Yang Meilin , Luan Yaqi , Wang Xining , Lv Zhimei
Published: January 2023

Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease and has gradually become a public health problem worldwide. DKD is increasingly recognized as a comprehensive inflammatory disease that is largely regulated by T cells. Given the pivotal role of T cells and T cells-producing cytokines in DKD, we summarized recent advances concerning T cells in the progression of type 2 diabetic nephropathy and provided a novel perspective of immune-related factors in diabetes. Specific emphasis is placed on the classification of T cells, process of T cell recruitment, function of T cells in the development of diabetic kidney damage, and potential treatments and therapeutic strategies involving T cells.
JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an in-vitro B cell differentiation model and in patients with rheumatoid arthritis
Authors: Frede Natalie , Lorenzetti Raquel , Hüppe Janika M , Janowska Iga , Troilo Arianna , Schleyer Marei-Theresa , Venhoff Ana C. , Voll Reinhard E. , Thiel Jens , Venhoff Nils , Rizzi Marta
Published: January 2023

Background

Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.

Methods

To this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on in-vitro B cell activation, proliferation, and class switch recombination and involved pathways.

Results

While B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an in-vitro model of T-cell-independent B cell activation we observed that JAK1/2 and selective JAK1 inhibitor treatment led to a dose-dependent decrease of total B cell numbers. We detected an altered B cell differentiation with a significant increase in MZ-like B cells and an increase in plasmablast differentiation in the first days of culture, most pronounced with the pan-JAK inhibitor tofacitinib, although there was no increase in immunoglobulin secretion in-vitro. Notably, we further observed a profound reduction of switched memory B cell formation, especially with JAK1/2 inhibition. JAK inhibitor treatment led to a dose-dependent reduction of STAT3 expression and phosphorylation as well as STAT3 target gene expression and modulated the secretion of pro- and anti-inflammatory cytokines by B cells.

Conclusion

JAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis.
Rapid screening and scaled manufacture of immunogenic virus-like particles in a tobacco BY-2 cell-free protein synthesis system
Authors: Armero-Gimenez Jorge , Wilbers Ruud , Schots Arjen , Williams Charles , Finnern Ricarda
Published: January 2023

Several vaccine platforms have been developed to fight pathogenic threats, with Virus-Like Particles (VLPs) representing a very promising alternative to traditional platforms. VLPs trigger strong and lasting humoral and cellular immune responses with fewer safety concerns and higher stability than other platforms. The use of extensively characterized carrier VLPs modified with heterologous antigens was proposed to circumvent the viral complexity of specific viruses that could lead to poor VLP assembly and yields. Although carrier VLPs have been successfully produced in a wide variety of cell-based systems, these are limited by low protein yields and protracted clone selection and optimization workflows that limit VLP screening approaches. In response, we have demonstrated the cell-free protein synthesis (CFPS) of several variants of the hepatitis B core (HBc) carrier VLP using a high-yielding tobacco BY-2 lysate (BYL). High VLP yields in the BYL system allowed in-depth characterization of HBc variants. Insertion of heterologous sequences at the spike region of the HBc monomer proved more structurally demanding than at the N-terminus but removal of the C-terminal domain allowed higher particle flexibility and insert acceptance, albeit at the expense of thermal and chemical stability. We also proved the possibility to scale the CFPS reaction up to 1L in batch mode to produce 0.45 grams of the native HBc VLP within a 48-hour reaction window. A maximum yield of 820 µg/ml of assembled VLP particles was observed at the 100µl scale and most remarkably the CFPS reaction was successfully scaled from 50µl to 1L without any reduction in protein yield across this 20,000-fold difference in reaction volumes. We subsequently proved the immunogenicity of BYL-derived VLPs, as flow cytometry and microscopy clearly showed prompt recognition and endocytosis of fluorescently labelled VLPs by human dendritic cells. Triggering of inflammatory cytokine production in human peripheral blood mononuclear cells was also quantitated using a multiplex assay. This research establishes BYL as a tool for rapid production and microscale screening of VLP variants with subsequent manufacturing possibilities across scales, thus accelerating discovery and implementation of new vaccine candidates using carrier VLPs.
Resistance to immune checkpoint inhibitors in advanced lung cancer: Clinical characteristics, potential prognostic factors and next strategy
Authors: Zhou Jiebai , Lu Xinyuan , Zhu Haixing , Ding Ning , Zhang Yong , Xu Xiaobo , Gao Lei , Zhou Jian , Song Yuanlin , Hu Jie
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs) have shown unprecedented clinical benefit in cancer immunotherapy and are rapidly transforming the practice of advanced lung cancer. However, resistance routinely develops in patients treated with ICIs. We conducted this retrospective study to provide an overview on clinical characteristics of ICI resistance, optimal treatment beyond disease progression after prior exposure to immunotherapy, as well as potential prognostic factors of such resistance.

Methods

190 patients diagnosed with unresectable lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/anti-programmed cell death-ligand 1(PD-L1) at any treatment line at Zhongshan Hospital Fudan University between Sep 2017 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed. Levels of plasma cytokines were evaluated for the prognostic value of ICI resistance.

Results

We found that EGFR/ALK/ROS1 mutation and receiving ICI treatment as second-line therapy were risk factors associated with ICI resistance. Patients with bone metastasis at baseline had a significantly shorter PFS1 time when receiving initial ICI treatment. Whether or not patients with oligo-progression received local treatment seemed to have no significant effect on PFS2 time. Systemic therapies including chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. TNF, IL-6 and IL-8 were significantly elevated when ICI resistance. Lower plasma TNF level and higher plasma IL-8 level seemed to be significantly associated with ICI resistance. A nomogram was established to prognosis the clinical outcome of patients treated with ICIs.

Conclusion

Patients with EGFR/ALK/ROS1 mutation, or those receiving ICI treatment as second-line therapy had higher risk of ICI resistance. Patients with bone metastasis had poor prognosis during immunotherapy. For those patients with oligo-progression after ICI resistance, combination with local treatment did not lead to a significantly longer PFS2 time. Chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. Levels of plasma cytokines including TNF, IL-6 and IL-8 were associated with ICI resistance.
Immunoinformatics design of multivalent epitope vaccine against monkeypox virus and its variants using membrane-bound, enveloped, and extracellular proteins as targets
Authors: Waqas Muhammad , Aziz Shahkaar , Liò Pietro , Khan Yumna , Ali Amjad , Iqbal Aqib , Khan Faizullah , Almajhdi Fahad Nasser
Published: January 2023

Introduction

The current monkeypox (MPX) outbreak, caused by the monkeypox virus (MPXV), has turned into a global concern, with over 59,000 infection cases and 23 deaths worldwide.

Objectives

Herein, we aimed to exploit robust immunoinformatics approach, targeting membrane-bound, enveloped, and extracellular proteins of MPXV to formulate a chimeric antigen. Such a strategy could similarly be applied for identifying immunodominant epitopes and designing multi-epitope vaccine ensembles in other pathogens responsible for chronic pathologies that are difficult to intervene against.

Methods

A reverse vaccinology pipeline was used to select 11 potential vaccine candidates, which were screened and mapped to predict immunodominant B-cell and T-cell epitopes. The finalized epitopes were merged with the aid of suitable linkers, an adjuvant (Resuscitation-promoting factor), a PADRE sequence (13 aa), and an HIV TAT sequence (11 aa) to formulate a multivalent epitope vaccine. Bioinformatics tools were employed to carry out codon adaptation and computational cloning. The tertiary structure of the chimeric vaccine construct was modeled via I-TASSER, and its interaction with Toll-like receptor 4 (TLR4) was evaluated using molecular docking and molecular dynamics simulation. C-ImmSim server was implemented to examine the immune response against the designed multi-epitope antigen.

Results and discussion

The designed chimeric vaccine construct included 21 immunodominant epitopes (six B-cell, eight cytotoxic T lymphocyte, and seven helper T-lymphocyte) and is predicted non-allergen, antigenic, soluble, with suitable physicochemical features, that can promote cross-protection among the MPXV strains. The selected epitopes indicated a wide global population coverage (93.62%). Most finalized epitopes have 70%–100% sequence similarity with the experimentally validated immune epitopes of the vaccinia virus, which can be helpful in the speedy progression of vaccine design. Lastly, molecular docking and molecular dynamics simulation computed stable and energetically favourable interaction between the putative antigen and TLR4.

Conclusion

Our results show that the multi-epitope vaccine might elicit cellular and humoral immune responses and could be a potential vaccine candidate against the MPXV infection. Further experimental testing of the proposed vaccine is warranted to validate its safety and efficacy profile.
The development of COVID-19 treatment
Authors: Yuan Yongliang , Jiao Baihai , Qu Lili , Yang Duomeng , Liu Ruijuan
Published: January 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic named coronavirus disease 2019 (COVID-19) that has become the greatest worldwide public health threat of this century. Recent studies have unraveled numerous mysteries of SARS-CoV-2 pathogenesis and thus largely improved the studies of COVID-19 vaccines and therapeutic strategies. However, important questions remain regarding its therapy. In this review, the recent research advances on COVID-19 mechanism are quickly summarized. We mainly discuss current therapy strategies for COVID-19, with an emphasis on antiviral agents, neutralizing antibody therapies, Janus kinase inhibitors, and steroids. When necessary, specific mechanisms and the history of therapy are present, and representative strategies are described in detail. Finally, we discuss key outstanding questions regarding future directions of the development of COVID-19 treatment.
Outcomes of feeding activity of the sea cucumber Holothuria tubulosa on quantity, biochemical composition, and nutritional quality of sedimentary organic matter
Authors: Pasquini Viviana , Addis Pierantonio , Giglioli Ambra Angelica , Moccia Davide , Pusceddu Antonio
Published: January 2023

Introduction

Holothuria tubulosa is one of the most common sea cucumbers in the Mediterranean Sea, generally associated with organically enriched coastal sediments and seagrass beds. As a deposit-feeder, it is responsible for strong bioturbation processes and plays a putative key role in sedimentary carbon cycling and benthic trophodynamics. With the aim of exploring the potential use of holothuroids as a tool for remediating eutrophicated sediments, we investigated the effects of H. tubulosa on sedimentary organic matter quantity, biochemical composition, and nutritional quality.

Methods

Holothuroids and associated samples of ambient sediments were collected in two sites located in the Central-Western Mediterranean Sea (Sardinia, Italy) and characterized by different trophic status backgrounds: the site of Oristano characterized by sandy-muddy sediments and the presence of mariculture plants (ranked as meso-eutrophic) and the site of Teulada characterized by sandy sediments and Posidonia oceanica meadows (ranked as oligo-mesotrophic). We compared the biochemical composition (proteins, carbohydrates, lipids) of ambient sediment vs sea cucumbers feces and the sedimentary protein content vs protein content in the sediments retrieved in different gut sections (esophagus, mid gut, end gut) of the holothuroid.

Results

Our results reveal that holothuroids feeding on meso-eutrophic sediments can increase protein (1.5 times) and lipid (1.3 times) content through their defecation, thus making these substrates a more labile food source for other benthic organisms. We report here that H. tubulosa feeding on meso-eutrophic sediment is most likely able to actively select particles rich in labile organic matter with buccal tentacles, as revealed by the protein content in the esophagus that is up to 2-folds higher than that in the source sediment. According to the inverse relationship between assimilation rates and availability of organic substrates and the optimal foraging theory, H. tubulosa feeding on oligo-mesotrophic sediments showed potential assimilation of proteins ca. 25% higher than that of specimens feeding on meso-eutrophic sediments.

Discussion

Our results reveal that H. tubulosa feeding on meso-eutrophic sediments can profoundly influence the benthic trophic status, specifically modifying the biochemical composition and nutritional quality of organic matter, thus paving the way to its possible use in bioremediation actions of eutrophicated sediments and in Integrated Multi-Trophic Aquaculture systems.
What controls the future phytoplankton change over the Yellow and East China Seas under global warming?
Authors: Lee Dong-Geon , Oh Ji-Hoon , Noh Kyung Min , Kwon Eun Young , Kim Young Ho , Kug Jong-Seong
Published: January 2023

The Yellow and East China Seas (YECS) are productive continental shelves where essential nutrients for phytoplankton growth are mainly supplied by the intrusion of the Kuroshio Current, riverine inputs, and atmospheric deposition. Surface temperatures in YECS are increasing due to global warming, and are projected to increase further. In this study, future changes in YECS biogeochemical processes were evaluated using Coupled Model Intercomparison Project Phase 6 (CMIP6) Earth System Models. We found a great diversity in predictions of future changes in chlorophyll-a over the YECS region. This diversity was determined to be closely related to the extent of phosphorus (P) limitation for phytoplankton growth. Models simulating positive chlorophyll changes tend to simulate increased Dissolved Inorganic Phosphate (DIP) supplies under future global warming. Our study also demonstrated that the intrusion of the Kuroshio Current into the YECS plays a critical role in future changes in DIP and chlorophyll-a by transporting relatively DIP-rich subsurface water from the Kuroshio Current into the marginal sea.
Genetic connectivity in Twospot flounder (Bothus robinsi) across the Gulf of Mexico, inferred with single nucleotide polymorphisms from larvae and adults
Authors: Morales-Pulido José Manuel , Munguia-Vega Adrian , Jiménez-Rosenberg Sylvia Patricia A. , Rocha-Olivares Axayacatl , Galindo-Sánchez Clara E.
Published: January 2023

Larval genetic information influences populations’ genetic pools, causing genetic homogenization or structuration. So, knowing about adult and larval genetic information is essential to understand processes such as connectivity. The aims are to evaluate Twospot flounder (Bothus robinsi, a fish with a high dispersal potential) larval pools’ genetic diversity, test if the larvae tend to mix or display collective dispersal, compare genetic information between larvae and adults and evaluate its connectivity. We used ddRADSEQ to genotype 1,034 single nucleotide polymorphic sites from B. robinsi larvae sampled in waters from the Bay of Campeche and the eastern Gulf of Mexico (GOM) and adults sampled on Florida’s continental shelf. Larvae were identified morphologically and by DNA barcoding. We estimated Fst-paired comparations, Principal Components Analysis (PCA), Discriminant Analyses of Principal Components (DAPC), and a Structure analysis to understand genetic trends. With the software COLONY, we made a sibship evaluation. We observed no significant heterogeneity among regions (Fst p-values>0.05). PCA, DAPC, and the Structure Analysis showed one genetic cluster, indicating genetic homogeneity. We did not detect full-sibs or half-sibs. We linked the results with the high dispersal potential of B. robinsi due to a long pelagic larval duration and the potential of ocean dynamics to transport and mix larvae from all GOM shelf areas. These findings suggest that the dispersal potential of B. robinsi is large enough to produce genetic connectivity in all GOM subpopulations and that time spent by its larvae in dispersal pathways is enough to mix larvae from different GOM subpopulations, indicating a panmictic population.
Setting the basis for transient DNA transformation and transformant selection in the red macroalga Gracilariopsis lemaneiformis
Authors: Eléouët Morgane , Zhang Ni , Guo Peng , Lei Yuehua , Kong Fanna , Sui Zhenghong
Published: January 2023

Gracilariopsis lemaneiformis (Gp. lemaneiformis) is an economically important agar-producing red alga applicable in the food and cosmetic industries. The genetic knowledge of this species is, however, limited, and genetic tools for studying and engineering it are lacking. This has limited the understanding of its developmental genetics and hindered the development of new strains, and developing genetic tools would allow to tackle these problems. Here, transient DNA transformation via microparticle bombardment is reported for the first time in this species, as well as efficient exogenous gene expression driven by the CaMV35S promoter, the endogenous GlAct1 promoter, and the Pyropia yezoensis PyAct1 promoter in the transformed branches. Moreover, the Blue Fluorescent Protein (BFP) is demonstrated to be a suitable reporter gene for studies in Gp. lemaneiformis. Screening of antibiotic sensitivity is needed for the development of transient DNA transformation, and selection of transformants is also reported in the alga. Hygromycin B (Hyg) is determined to be the most effective antibiotic for Gp. lemaneiformis selection. The Hyg resistance gene driven by the CaMV35S promoter is shown to confer resistance to Hyg at a concentration of 1 mg.ml-1, but no transformed individual could be regenerated so far. These results are promising for future refining of the experimental conditions, for instance, by using different promoters and developing techniques for facilitating the penetration of the DNA in the cells.
Genetic linkage map construction and QTL mapping of blade length and width in Saccharina japonica using SSR and SNP markers
Authors: Wang Xiuliang , Yang Xiaoqi , Yao Jianting , Li Qiuying , Lu Chang , Duan Delin
Published: January 2023

MAS (marker assisted selection) is useful for cultivar development in the lower plant Saccharina japonica. In this study, 167 screened SSR markers and 125 individuals were used to construct a S.japonica genetic linkage map with 27 linkage groups and a total Haldane length of 2069 cM. Constructed linkage groups were aligned with assembled pseudo-chromosomes of S. japonica genome sequences (NCBI: MEHQ00000000) and anchored to 23 of 31 pseudo-chromosomes. A genetic linkage map including 33 linkage groups was constructed with combined 3397 SSR and SNP markers. In the integrated genetic map used for QTL mapping, SSR marker M1895 was closely associated with the major QTL for blade length and width with LOD threshold of >5.0. Annotation indicated that SjPT, coded as a high affinity phosphate transporter, was mapped to this major QTL with cDNA sequence of 1422 bp, which coded 473 aa for 8 transmembrane helics. qRT-PCR and the transcriptomic detection confirmed that SjPT transcription was consistent with increases in kelp blade length and width. Marker M1895 appears to be particularly useful for MAS (marker assisted selection) in S. japonica breeding.
Standardized classification schemes in reporting oncologic PET/CT
Authors: Murad Vanessa , Kulanthaivelu Roshini , Ortega Claudia , Veit-Haibach Patrick , Metser Ur
Published: January 2023

The imaging report is essential for the communication between physicians in patient care. The information it contains must be clear, concise with evidence-based conclusions and sufficient to support clinical decision-making. In recent years, several classification schemes and/or reporting guidelines for PET have been introduced. In this manuscript, we will review the classifications most frequently used in oncology for interpreting and reporting 18F-FDG PET imaging in lymphoma, multiple myeloma, melanoma and head and neck cancers, PSMA-ligand PET imaging for prostate cancer, and 68Ga-DOTA-peptide PET in neuroendocrine tumors (NET).
Case report:Multiple abscesses caused by Porphyromonas gingivalis diagnosed by metagenomic next-generation sequencing
Authors: Zhang Yichen , Zhu Youfeng , Wan Huijuan
Published: January 2023

Background

Extraoral infection by Porphyromonas gingivalis (P. gingivalis) is extremely rare and challenging to diagnose because the fastidious pathogen is difficult to culture by traditional methods. We report the first case of a patient with multiple abscesses in muscles and the brain with dura empyema due to P. gingivalis, which was diagnosed by metagenomic next-generation sequencing (mNGS).

Case presentation

A 65-year-old male patient was admitted to our hospital for multiple lumps in his body. Brain magnetic resonance imaging (MRI) and lower-limb computed tomography (CT) revealed multiple abscesses in the brain and muscles. A diagnosis of P. gingivalis infection was made based on mNGS tests of blood, cerebrospinal fluid (CSF), and pus samples, as the traditional bacterial culture of these samples showed negative results. Target antibiotic therapy with meropenem and metronidazole was administered, and CT-guided percutaneous catheter drainage of abscesses in both thighs was performed. The size of muscle abscesses reduced significantly and neurological function improved. The patient was followed up for 4 months. No abscesses re-appeared, and the remaining abscesses in his backside and both legs were completely absorbed. He can speak fluently and walk around freely without any neurological deficits.

Conclusion

Metagenomic next-generation sequencing is helpful for early diagnosis and subsequent treatment of P. gingivalis-associated multiple abscesses.