bluuebunny/crossref_metadata_2025 huggingface dataset:
Septodermoplasty in Recurrent Epistaxis Without Hereditary Hemorrhagic Telangiectasia
Authors: Lee Yeong Ju , Jang Yong Ju
Published: February 2023

Epistaxis is a common disease, most of which is naturally improved without treatment. However, some patients experience recurrent epistaxis despite having received various treatments. In such cases, the control of epistaxis may require a more invasive technique, such as embolization or surgical ligation of the main feeding arteries of the nasal cavity. However, the nasal septum receives blood supply from various branches of blood vessels, so these vascular controls can be inappropriate. In this case report, we applied septodermoplasty - a surgical technique mostly aimed for the treatment of intractable epistaxis from hereditary hemorrhagic telangiectasia (HHT) - to treat patients suffering recurrent epistaxis from the nasal septum. Although the two patients we treated were non-HHT, our application of this surgical technique turned out to be successful. Here, we suggest expanding the indication of septodermoplasty to non-HHT patients presenting with recurrent and difficult-to-treat epistaxis.
Усиление железобетонных балок сталефибробетоном с учетом предыстории нагружения
Authors: РАДАЙКИН Олег Валерьевич , ШАРАФУТДИНОВ Линар Альфредович
Published: February 2023

Проведено экспериментальное исследование железобетонных балок, усиленных сталефибробетонной "рубашкой", в процессе которого изучено влияние пяти факторов - толщины "рубашки", уровня нагрузки до момента усиления, уровня нагрузки при проведении работ по усилению, коэффициента фибрового армирования "рубашки" по объему, длительности действия нагрузки после усиления. Получены данные по прочности, жесткости, трещиностойкости и напряженно-деформированному состоянию для балок, усиленных такой "рубашкой", и контрольных (без усиления). За счет усиления удалось значительно увеличить несущую способность балок, их трещиностойкость и жесткость в стадии эксплуатации. Эксперимент позволил выявить оптимальные параметры и область применения усиления балок с помощью сталефибробетонной "рубашки". Определены оптимальные толщина рассмотренных конструкций балок, длина "рубашки", а также оптимальный коэффициент фибрового армирования. Применение рассматриваемого способа усиления эффективно для балок небольших пролетов, при этом уровень начального нагружения не должен превышать 70 % разрушающей нагрузки неусиленной балки.
A universal GlycoDesign for lysosomal replacement enzymes to improve circulation time and biodistribution
Authors: Chen Yen-Hsi , Tian Weihua , Yasuda Makiko , Ye Zilu , Song Ming , Mandel Ulla , Kristensen Claus , Povolo Lorenzo , Marques André R. A. , Čaval Tomislav , Heck Albert J. R. , Sampaio Julio Lopes , Johannes Ludger , Tsukimura Takahiro , Desnick Robert , Vakhrushev Sergey Y. , Yang Zhang , Clausen Henrik
Published: February 2023

Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due in part to short circulation times and suboptimal biodistribution of the therapeutic enzymes. We previously engineered Chinese hamster ovary (CHO) cells to produce α-galactosidase A (GLA) with various N-glycan structures and demonstrated that elimination of mannose-6-phosphate (M6P) and conversion to homogeneous sialylated N-glycans prolonged circulation time and improved biodistribution of the enzyme following a single-dose infusion into Fabry mice. Here, we confirmed these findings using repeated infusions of the glycoengineered GLA into Fabry mice and further tested whether this glycoengineering approach, Long-Acting-GlycoDesign (LAGD), could be implemented on other lysosomal enzymes. LAGD-engineered CHO cells stably expressing a panel of lysosomal enzymes [aspartylglucosamine (AGA), beta-glucuronidase (GUSB), cathepsin D (CTSD), tripeptidyl peptidase (TPP1), alpha-glucosidase (GAA) or iduronate 2-sulfatase (IDS)] successfully converted all M6P-containing N-glycans to complex sialylated N-glycans. The resulting homogenous glycodesigns enabled glycoprotein profiling by native mass spectrometry. Notably, LAGD extended the plasma half-life of all three enzymes tested (GLA, GUSB, AGA) in wildtype mice. LAGD may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
Dysregulated proteostasis network in neuronal diseases
Authors: Tseng Ching-San , Chao Yu-Wen , Liu Yi-Hsiang , Huang Yi-Shuian , Chao Hsu-Wen
Published: February 2023

Long-term maintenance of synaptic connections is important for brain function, which depends on varying proteostatic regulations to govern the functional integrity of neuronal proteomes. Proteostasis supports an interconnection of pathways that regulates the fate of proteins from synthesis to degradation. Defects in proteostatic signaling are associated with age-related functional decline and neurodegenerative diseases. Recent studies have advanced our knowledge of how cells have evolved distinct mechanisms to safely control protein homeostasis during synthesis, folding and degradation, and in different subcellular organelles and compartments. Neurodegeneration occurs when these protein quality controls are compromised by accumulated pathogenic proteins or aging to an irreversible state. Consequently, several therapeutic strategies, such as targeting the unfolded protein response and autophagy pathways, have been developed to reduce the burden of misfolded proteins and proved useful in animal models. Here, we present a brief overview of the molecular mechanisms involved in maintaining proteostatic networks, along with some examples linking dysregulated proteostasis to neuronal diseases.
Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization
Authors: Jaramillo Josue , Taylor Caroline , McCarley Rachel , Berger Melissa , Busse Emily , Sammarco Mimi C.
Published: February 2023

Cell metabolism coordinates the biochemical reactions that produce carbon and ATP in order for the cell to proliferate, differentiate, and respond to environmental changes. Cell type determines metabolic demand, so proliferating skeletal progenitors and differentiated osteoblasts exhibit different levels of cell metabolism. Limb regeneration is an energetically demanding process that involves multiple types of tissues and cell functions over time. Dysregulation of cell metabolism in aged mice results in impaired regeneration, a defect that can be rescued in part by the administration of oxaloacetate (OAA). A better understanding of how cell metabolism regulates regeneration in general, and how these changes can be modulated to benefit potential regenerative strategies in the future is needed. Here we sought to better understand the effects of OAA on young mice and determine whether the same mechanism could be tapped to improve regeneration without an aged-defect. We also asked which dosing time periods were most impactful for promoting regenerative outcomes, and whether these effects were sustained after dosing was stopped. Consistent with our findings in aged mice we found that OAA enhanced regeneration by accelerating bone growth, even beyond control measures, by increasing trabecular thickness, decreasing trabecular spacing, and improving the patterning by decreasing the taper, making the regenerated bone more like an unamputated digit. Our data suggests that the decrease in spacing, an improvement over aged mice, may be due to a decrease in hypoxia-driven vasculature. Our findings suggest that OAA, and similar metabolites, may be a strong tool to promote regenerative strategies and investigate the mechanisms that link cell metabolism and regeneration.
Quantitative and qualitative analyses of grafted okra for corrosion inhibition of mild steel in acidic medium
Authors: Sulaimon Aliyu Adebayo , Murungi Pearl Isabellah , Tackie-Otoo Bennet Nii , Nwankwo Princess Christiana , Bustam Mohamad Azmi
Published: February 2023

Introduction: Natural plant polymers demonstrate effective corrosion inhibition abilities, because of their numerous binding sites and excellent adsorption abilities.

Methodology: In this study, the Box-Behnken method, gravimetric and electrochemical analyses were used to design and investigate the corrosion inhibition potential of a modified graft polymer of okra for mild steel in a 1M HCl medium. The influence of inhibitor concentration, temperature, and time were also investigated. Qualitatively, the Fourier Transform Infrared (FTIR) spectroscopy, Thermogravimetric Analysis (TGA), and Field emission scanning electron microscopy (FESEM) were used to characterize the extracts and evaluate the metal’s surface morphology.

Results and discussion: The quantitative analyses showed that the modified natural polymer’s inhibition efficiency (IE) increased with concentration and reached 73.5% at 800 ppm, with a mixed-type mode of inhibition. From the response surface methodology, it was revealed that temperature influences the IE more than concentration and immersion time. The optimized IE using the desirability function showed the possibility of attaining 88.2% inhibition with inhibitor concentration at 142.3 ppm, temperature at 60.4°C, and an immersion time of 22.4 h. The new functional groups in the hybrid polymer revealed by FTIR analysis shows that grafting improved the inhibitor’s adsorption abilities. TGA analysis confirmed the extract’s high thermal stability, which highlights the inhibitor’s strong adsorption and efficiency for high temperatures. FESEM analysis indicated evidence of inhibitor adsorption onto the metal surface.

Conclusion: These findings suggest that the grafting of okra with acrylamide enhances its inhibition properties and contributes to its functionality as a cost-effective plant-based alternative inhibitor against corrosion for mild steel facilities.
Case report: A clinical case study of six patients with Chlamydia psittaci pneumonia
Authors: Dai Jinmeng , Lian Xue , Mo Juanfen , Li Xiaosi , Mo Weiqiang , Wang Haiqin , Jiang Jianping
Published: February 2023

Objective

To investigate the clinical features, diagnosis, and treatment of Chlamydia psittaci (C. psittaci) pneumonia.

Methods

We retrospectively analyzed the clinical data of six patients with C. psittaci pneumonia who were admitted to the Division of Pulmonary and Critical Care Medicine of the Second Hospital of Jiaxing from December 2021 to September 2022.

Results

All patients reported a fever and other accompanying symptoms, including cough (5/6), chest tightness (1/6), fatigue (2/6), and headache (1/6). Laboratory results showed that all patients had high levels of C-reactive protein (CRP≥70 mg/L), procalcitonin (PCT; 2 patients with PCT levels ≥0.5 ng/L), and erythrocyte sedimentation rate (ESR). Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels were elevated in 3/6 and of 2/6 patients, respectively. Chest computed tomography (CT) of most patients showed patchy, high-density shadows with partial consolidation, accompanied by air bronchogram signs and pleural effusion. Six patients were diagnosed with C. psittaci pneumonia using metagenomic next-generation sequencing (mNGS). They showed favorable outcomes following immediate adjustment of the regimen to doxycycline-based therapy and hydration, nutrition, and other follow-up treatments. In the imaging findings obtained at one-two month, the lesions were completely cleared, suggesting a favorable prognosis.

Conclusion

Patients with C. psittaci pneumonia commonly present sepsis and rapidly progressing disease. Early diagnosis is critical for C. psittaci pneumonia using mNGS, which can lead to favorable prognoses via immediate adjustment therapies.
End-of-treatment anti-HBs levels and HBeAg status identify durability of HBsAg loss after PEG-IFN discontinuation
Authors: Guo Yifei , Han Jiajia , Zhang Yongmei , Jin Chengmeng , Zhang Yao , He Jingjing , Chen Shiqi , Guo Yue , Lin Yanxue , Li Fahong , Yang Feifei , Shen Zhongliang , Mao Richeng , Zhu Haoxiang , Zhang Jiming
Published: February 2023

Background

Hepatitis B surface antigen (HBsAg) loss, namely, the functional cure, can be achieved through the pegylated interferon (PEG-IFN)-based therapy. However, it is an unignorable fact that a small proportion of patients who achieved functional cure develop HBsAg reversion (HRV) and the related factors are not well described.

Methods

A total of 112 patients who achieved PEG-IFN-induced HBsAg loss were recruited. HBV biomarkers and biochemical parameters were examined dynamically. HBV RNA levels were assessed in the cross-sectional analysis. The primary endpoint was HRV, defined as the reappearance of HBsAg after PEG-IFN discontinuation.

Results

HRV occurred in 17 patients during the follow-up period. Univariable analysis indicated that hepatitis B e antigen (HBeAg) status, different levels of hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) at the end of PEG-IFN treatment (EOT) were significantly associated with the incidence of HRV through using the log-rank test. Additionally, time-dependent receiver operating characteristic (ROC) analysis showed that the anti-HBs was superior to anti-HBc in predictive power for the incidence of HRV during the follow-up period. Multivariable Cox proportional hazard analysis found that anti-HBs ≥1.3 log10IU/L (hazard ratio (HR), 0.148; 95% confidence interval (CI), 0.044-0.502) and HBeAg negativity (HR, 0.183; 95% CI, 0.052-0.639) at EOT were independently associated with lower incidence of HRV. Cross-sectional analysis indicated that the HBV RNA levels were significantly correlated with the HBsAg levels in patients with HRV (r=0.86, p=0.003).

Conclusions

EOT HBeAg negativity and anti-HBs ≥1.3 log10IU/L identify the low risk of HRV after PEG-IFN discontinuation.
Future projections of seasonal temperature and precipitation for India
Authors: Salunke Popat , Keshri Narayan Prasad , Mishra Saroj Kanta , Dash S. K.
Published: February 2023

Ninety climate models, from four consortiums—CMIP5, CMIP6, NEX-GDDP, and CORDEX—are evaluated for the simulation of seasonal temperature and precipitation over India, and subsequently, using the best ones, their future projections are made for the country. NEX-GDDP is found to be the best performer for the simulation of surface air temperature for all the four seasons. For the simulation of precipitation, CMIP6 performs the best in DJF and MAM seasons, while NEX-GDDP performs the best in JJAS and ON seasons. The selected models suggest that temperature will increase over the entire Indian landmass, relatively more over the north-western part of the country. Furthermore, the rate of warming will be more in winter than in summer. The models also suggest that precipitation will increase over central eastern and north-eastern India in the monsoon season, and over peninsular India during post-monsoon months.
Systematic analysis of myocardial immune progression in septic cardiomyopathy: Immune-related mechanisms in septic cardiomyopathy
Authors: Ma Dunliang , Qin Xianyu , Zhong Zhi-an , Liao Hongtao , Chen Pengyuan , Zhang Bin
Published: February 2023

Background

The immune infiltration and molecular mechanisms underlying septic cardiomyopathy (SC) have not been completely elucidated. This study aimed to identify key genes related to SC and elucidate the potential molecular mechanisms.

Methods

The weighted correlation network analysis (WGCNA), linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, CIBERSORT, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and gene set enrichment analysis (GSEA) were applied to assess the key pathway and hub genes involved in SC.

Results

We identified 10 hub genes, namely, LRG1, LCN2, PTX3, E LANE, TCN1, CLEC4D, FPR2, MCEMP1, CEACAM8, and CD177. Furthermore, we used GSEA for all genes and online tools to explore the function of the hub genes. Finally, we took the intersection between differential expression genes (DEGs) and hub genes to identify LCN2 and PTX3 as key genes. We found that immune-related pathways played vital roles in SC. LCN2 and PTX3 were key genes in SC progression, which mainly showed an anti-inflammatory effect. The significant immune cells in cardiomyocytes of SC were neutrophils and M2 macrophages.

Conclusion

These cells may have the potential to be prognostic and therapeutic targets in the clinical management of SC. Excessive anti-inflammatory function and neutrophil infiltration are probably the primary causes of SC.
Quantifying the contributions of climate factors and human activities to variations of net primary productivity in China from 2000 to 2020
Authors: Li Zijian , Chen Jiangping , Chen Zhanpeng , Sha Zongyao , Yin Jianhua , Chen Zhaotong
Published: February 2023

Net primary productivity (NPP) plays a vital role in the globe carbon cycle. Quantitative assessment of the effects of climate changes and human activities on net primary productivity dynamics is vital for understanding the driving mechanisms of vegetation change and sustainable development of ecosystems. This study investigates the contributions of climatic factors and human activities to vegetation productivity changes in China from 2000 to 2020 based on the residual trend analysis (RESTREND) method. The results showed that the annual average net primary productivity in China was 325.11 g C/m2/year from 2000 to 2020 and net primary productivity showed a significantly increasing trend (p<0.05) at a rate of 2.32 g C/m2/year. Net primary productivity increased significantly (p<0.05) across 40.90% of China over the study period, while only 1.79% showed a significantly declining trend (p<0.05). The contributions of climatic factors and human activities to net primary productivity increase were 1.169 g C/m2/year and 1.142 g C/m2/year, respectively. Climate factors contributed positively mainly in Sichuan Basin, the Loess Plateau, the Mongolian Plateau, and Northeast China Plain. Positive contributions of human activities to net primary productivity mainly occurred in the Loess Plateau, Central China, and the Greater Khingan Mountains. The effects of climatic factors and human activities on net primary productivity changes varied among sub-regions. In Tropical Monsoon Climate Region and Subtropical Monsoon Climate Region, human activities had greater impacts on net primary productivity increase than climate factors, while climate factors were the dominant factor for net primary productivity recovery in other sub-regions. In addition, during 2000–2020, net primary productivity was dominated by both climate factors and human activities in 49.84% of China, while areas dominated solely by climate factors and human activities accounted for 13.67% and 10.92%, respectively. Compared to changed land cover types, the total net primary productivity as well as the increase of total net primary productivity in China was mostly contributed by unchanged land cover types, which contributed more than 90%.
Direct and indirect effects of fibroblast growth factor 23 on the heart
Authors: Nakano Toshiaki , Kishimoto Hiroshi , Tokumoto Masanori
Published: February 2023

Fibroblast growth factor (FGF)23 is a bone-derived phosphotropic hormone that regulates phosphate and mineral homeostasis. Recent studies have provided evidence that a high plasma concentration of FGF23 is associated with cardiac disease, including left ventricular hypertrophy (LVH), heart failure, atrial fibrillation, and cardiac death. Experimental studies have shown that FGF23 activates fibroblast growth factor receptor 4 (FGFR4)/phospholipase Cγ/calcineurin/nuclear factor of activated T-cells signaling in cardiomyocytes and induces cardiac hypertrophy in rodents. Activation of FGFR4 by FGF23 normally requires the co-receptor α-klotho, and klotho-independent signaling occurs only under conditions characterized by extremely high FGF23 concentrations. Recent studies have demonstrated that FGF23 activates the renin-angiotensin-aldosterone system (RAAS) and induces LVH, at least in part as a result of lower vitamin D activation. Moreover, crosstalk between FGF23 and RAAS results in the induction of cardiac hypertrophy and fibrosis. In this review, we summarize the results of studies regarding the relationships between FGF23 and cardiac events, and describe the potential direct and indirect mechanisms whereby FGF23 induces LVH.
A rare homozygous variant of MC2R gene identified in a Chinese family with familial glucocorticoid deficiency type 1: A case report
Authors: Liu ShuPing , Zeng Ting , Luo Cheng , Peng DanXia , Xu Xuan , Liu Qin , Wu Qiong , Lu Qin , Huang FuRong
Published: February 2023

Background

Melanocortin-2 receptor (MC2R), a member of the G protein-coupled receptor family, is selectively activated by adrenocorticotropic hormone (ACTH). variants in MC2R are associated with family glucocorticoid deficiency 1 (FGD1).

Case presentation

We first reported a Chinese family with two affected siblings with a homozygotic variant of c.712C>T/p.H238Y in MC2R, presenting with skin hyperpigmentation, hyperbilirubinemia, and tall stature. These individuals showed novel clinical features, including congenital heart defects, not been found in other FGD1 patients.

Conclusions

We reported a Chinese family with affected siblings having a homozygotic variant of c.712C>T/p.H238Y in MC2R.Our report may expand the genetic and clinical spectrum of FGD1.
Clinical symptoms, thyroid dysfunction, and metabolic disturbances in first-episode drug-naïve major depressive disorder patients with suicide attempts: A network perspective
Authors: Peng Pu , Wang Qianjin , Lang Xiaoe , Liu Tieqiao , Zhang Xiang-Yang
Published: February 2023

Backgrounds

Co-occurrence of thyroid dysfunction, metabolic disturbances, and worsening clinical symptoms in major depressive disorder (MDD) patients with suicidal attempts (SA) are common. However, their relationship in SA patients remains unexplored. We aimed to (1) determine the independent association of thyroid dysfunction, clinical symptoms, and metabolic disturbances with SA; and (2) identify their interactions in SA patients via the network approach.

Methods

1718 FEDN MDD patients were recruited. Depressive, anxiety, and psychotic symptoms were assessed by the Hamilton Rating Scale for Depression (HAMD), the Hamilton Rating Scale for Anxiety (HAMA), and the Positive and Negative Syndrome Subscale positive subscale, respectively. The serum levels of thyroid hormones and other metabolic parameters were assessed. Logistic regression model was applied to determine the correlates of SA. Network analysis was applied to determine the interaction between thyroid dysfunction, clinical symptoms, and metabolic disturbances.

Results

SA patients had significant worse metabolic disturbances, thyroid dysfunction, and clinical symptoms than non-SA patients. Thyroid peroxidases antibody, thyroid stimulating hormone (TSH), HAMD scores, HAMA scores, and systolic blood pressure was independently associated with SA. Network analysis suggested that TSH was the hub of the network, exhibiting substantial associations with metabolic disturbances, anxiety, and psychotic symptoms in SA patients.

Conclusions

Our work highlights the predominant role of serum TSH levels in the pathophysiology of SA. Regular thyroid function tests might help early detect SA. Targeting increased TSH levels may help reduce metabolic disturbances and clinical symptoms in SA patients.
A novel digital control scheme for power management in a hybrid energy-source environment pertaining to electric vehicle applications
Authors: Mathesh G. , Saravanakumar R.
Published: February 2023

In electric vehicle, the utilization of various input power sources demand an appropriate integration. This integration inevitably questions the effectiveness of a suitable power management system. The integration of sources causes complexity in power conversion and programming errors while switching between the sources and brings difficulties in real-time implementation. This study presents a novel digital control scheme specific to the integration of solar, battery, and fuel cell to solve these issues and also explains the power management system in different controllers for electric vehicles. The proposed scheme checks the reference currents based on the power generated by the different sources needed to meet the instantaneous demand from the permanent magnet synchronous machine, which is widely used in electric vehicles. The methodology constitutes maximum power point tracking in solar panels at every second of the day, retaining constant voltage in the DC bus and managing the power flow from sources to the permanent magnet synchronous machine based on the power availability from different sources. The power flow to a control module dedicated to permanent magnet synchronous machine control is considered. The major contribution of the paper is the design and development of a power management system for an electric vehicle with a novel digital control scheme. Power management is achieved with the aid of a digital controller using real-time solar data for a periodically fluctuating load demand in MATLAB/Simulink and also in an experimental investigation, the results of which are discussed.
The impact of urban sprawl on green total factor productivity: A spatial econometric analysis in China
Authors: Liu Shucheng , Wu Peijin
Published: February 2023

The rapid expansion of Chinese cities has led to serious urban productivity and eco-environment changes, and has therefore attracted considerable international academic attention. The main objective of this study is to investigate the theoretical mechanisms and practical effects of urban sprawl on green total factor productivity (GTFP), in order to provide a reference for optimizing the spatial layout of cities and promoting high-quality economic development. Realistic urban land area and population characteristics are extracted using DMSP/OLS and NPP/VIIRS nighttime lighting data, and LandScan global population dynamics statistics to measure the urban sprawl index. GTFP is measured using a super-SBM model that considers undesirable output. Based on the panel data of Chinese cities from 2006 to 2020, a spatial Durbin model was constructed to carry out the empirical analysis. The results show that, overall, urban sprawl in China is detrimental to its own GTFP, while contributing to the GTFP of neighboring cities. The impacts of urban sprawl vary markedly across cities of different sizes and across regions.
Uncertainty propagation in a global biogeochemical model driven by leaf area data
Authors: Bian Chenyu , Xia Jianyang
Published: February 2023

Satellite-observed leaf area index (LAI) is often used to depict vegetation canopy structure and photosynthesis processes in terrestrial biogeochemical models. However, it remains unclear how the uncertainty of LAI among different satellite products propagates to the modeling of carbon (C), nitrogen (N), and phosphorus (P) cycles. Here, we separately drive a global biogeochemical model by three satellite-derived LAI products (i.e., GIMMS LAI3g, GLASS, and GLOBMAP) from 1982 to 2011. Using a traceability analysis, we explored the propagation of LAI-driven uncertainty to modeled C, N, and P storage among different biomes. The results showed that the data uncertainty of LAI was more considerable in the tropics than in non-tropical regions, whereas the modeling uncertainty of C, N, and P stocks showed a contrasting biogeographic pattern. The spread of simulated C, N, and P storage derived by different LAI datasets resulted from assimilation rates of elements in shrubland and C3 grassland but from the element residence time (τ) in deciduous needle leaf forest and tundra regions. Moreover, the assimilation rates of elements are the main contributing factor, with 67.6, 93.2, and 93% of vegetated grids for the modeled uncertainty of C, N, and P storage among the three simulations. We further traced the variations in τ to baseline residence times of different elements and the environmental scalars. These findings indicate that the data uncertainty of plant leaf traits can propagate to ecosystem processes in global biogeochemical models, especially in non-tropical forests.
A cuproptosis-related LncRNA signature: Integrated analysis associated with biochemical recurrence and immune landscape in prostate cancer
Authors: Ren Lei , Yang Xu , Wang Weifeng , Lin Hansen , Huang Guankai , Liu Zixiong , Pan Jincheng , Mao Xiaopeng
Published: February 2023

Background: As a new form of regulated cell death, cuproptosis differs profoundly from apoptosis, ferroptosis, pyroptosis, and necroptosis. The correlation between cuproptosis and long non-coding RNAs (lncRNAs) has been increasingly studied recently. In this study, a novel cuproptosis-related lncRNA prognostic signature was developed to investigate biochemical recurrence (BCR) and tumor immune landscape in prostate cancer (PCa).

Methods and Materials: The transcriptome data and clinicopathologic information of PCa patients were downloaded from The Cancer Genome Atlas (TCGA). Pearson’s correlation analysis was applied to identify lncRNAs associated with cuproptosis. Based on Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a cuproptosis-related lncRNA prognostic model (risk score) to predict the BCR of PCa patients. Additionally, we also constructed a nomogram with the risk score and clinicopathologic features. The biological function, tumor mutation burden (TMB), immune cell infiltration, expression levels of immune checkpoint genes, and anti-cancer drug sensitivity were investigated.

Results: We constructed and validated the cuproptosis-related lncRNA signature prognostic model (risk score) by six crlncRNAs. All patients were divided into the low- and high-risk groups based on the median risk score. The Kaplan–Meier (KM) survival analysis revealed that the high-risk group had shorter BCR-free survival (BCRFS). The risk score has been proven to be an independent prognostic factor of BCR in PCa patients. In addition, a nomogram of risk scores and clinicopathologic features was established and demonstrated an excellent predictive capability of BCR. The ROC curves further validated that this nomogram had higher accuracy of predicting the BCR compared to other clinicopathologic features. We also found that the high-risk group had higher TMB levels and more infiltrated immune cells. Furthermore, patients with high TMB in the high-risk group were inclined to have the shortest BCRFS. Finally, patients in the high-risk group were more susceptible to docetaxel, gefitinib, methotrexate, paclitaxel, and vinblastine.

Conclusion: The novel crlncRNA signature prognostic model shows a greatly prognostic prediction value of BCR for PCa patients, extends our thought on the association of cuproptosis and PCa, and provides novel insights into individual-based treatment strategies for PCa.
From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer
Authors: Chen Beibei , Hu Huihui , Chen Xiaobing
Published: February 2023

Cancerous inhibitor of protein phosphatase 2A (CIP2A), initially reported as a tumor-associated antigen (known as p90), is highly expressed in most solid and hematological tumors. The interaction of CIP2A/p90, protein phosphatase 2A (PP2A), and c-Myc can hinder the function of PP2A toward c-Myc S62 induction, thus stabilizing c-Myc protein, which represents a potential role of CIP2A/p90 in tumorigeneses such as cell proliferation, invasion, and migration, as well as cancer drug resistance. The signaling pathways and regulation networks of CIP2A/p90 are complex and not yet fully understood. Many previous studies have also demonstrated that CIP2A/p90 can be used as a potential therapeutic cancer target. In addition, the autoantibody against CIP2A/p90 in sera may be used as a promising biomarker in the diagnosis of certain types of cancer. In this Review, we focus on recent advances relating to CIP2A/p90 and their implications for future research.
New-age vaccine adjuvants, their development, and future perspective
Authors: Verma Shailendra Kumar , Mahajan Pooja , Singh Nikhlesh K. , Gupta Ankit , Aggarwal Rupesh , Rappuoli Rino , Johri Atul Kumar
Published: February 2023

In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of vaccinology, there is a need to not only develop safe and ideal vaccines to fight deadly infections but also improve the quality of existing vaccines in terms of partial or inconsistent protection. Generally, subunit vaccines are known to be safe in nature, but they are mostly found to be incapable of generating the optimum immune response. Hence, there is a great possibility of improving the potential of a vaccine in formulation with novel adjuvants, which can effectively impart superior immunity. The vaccine(s) in formulation with novel adjuvants may also be helpful in fighting pathogens of high antigenic diversity. However, due to the limitations of safety and toxicity, very few human-compatible adjuvants have been approved. In this review, we mainly focus on the need for new and improved vaccines; the definition of and the need for adjuvants; the characteristics and mechanisms of human-compatible adjuvants; the current status of vaccine adjuvants, mucosal vaccine adjuvants, and adjuvants in clinical development; and future directions.
Highly purified and functionally stable in vitro expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation
Authors: Arteaga-Cruz Saúl , Cortés-Hernández Arimelek , Alvarez-Salazar Evelyn Katy , Rosas-Cortina Katya , Aguilera-Sandoval Christian , Morales-Buenrostro Luis E. , Alberú-Gómez Josefina M. , Soldevila Gloria
Published: February 2023

The development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the co-expression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated. Here, we establish a new protocol that allows long-term in vitro expansion of highly purified expanded allospecific Tr1 (Exp-allo Tr1). Our expanded Tr1 cell population becomes highly enriched in IL-10 producers (> 90%) and maintains high expression of CD49b and LAG-3, as well as the co-inhibitory receptors PD-1, CTLA-4, TIM-3, TIGIT and CD39. Most importantly, high dimensional analysis of Exp-allo Tr1 demonstrated a specific expression profile that distinguishes them from activated conventional T cells (T conv), showing overexpression of IL-10, CD39, CTLA-4 and LAG-3. On the other hand, Exp-allo Tr1 expressed a chemokine receptor profile relevant for allograft homing and tolerance induction including CCR2, CCR4, CCR5 and CXCR3, but lower levels of CCR7. Interestingly, Exp-allo Tr1 efficiently suppressed allospecific but not third-party T cell responses even after being expanded in the presence of proinflammatory cytokines for two extra weeks, supporting their functional stability. In summary, we demonstrate for the first time that highly purified allospecific Tr1 (Allo Tr1) cells can be efficiently expanded maintaining a stable phenotype and suppressive function with homing potential to the allograft, so they may be considered as promising therapeutic tools for solid organ transplantation.
Single-cell transcriptomic analysis in two patients with rare systemic autoinflammatory diseases treated with anti-TNF therapy
Authors: Hua Yichao , Wu Na , Miao Junke , Shen Min
Published: February 2023

Systemic autoinflammatory diseases (SAIDs) are a group of rare diseases characterized by recurrent or continuous inflammation, typically accompanied by genetic variants. Good responses to anti-TNF therapy were observed in SAIDs patients. However, the mechanisms underlying the disease flare and the response to TNF blocking therapy have not been fully elucidated. Here, single-cell RNA sequencing technology was used to describe the transcriptomic profile of PBMCs and PMNs in two SAID patients both before and after anti-TNF treatment. Interferon responses were involved in the disease flare. After anti-TNF therapy, clinical symptoms were alleviated while TNF and IL-1 were unexpectedly increased, indicating that these inflammatory cytokines are not positively correlated with disease activity. Trajectory analysis showed that inhibition of macrophage differentiation, rather than reduction of the inflammatory cytokines, as the potential mechanism of anti-TNF treatment response in SAIDs.
Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies
Authors: Li Zhuoqi , Gao Ziyu , Sun Tao , Zhang Shipeng , Yang Shengnan , Zheng Meilin , Shen Hui
Published: February 2023

Meteorin-like, also known as Metrnl, Meteorin-β, Subfatin, and Cometin, is a novel secreted protein exerting pleiotropic effects on inflammation, immunology, and metabolism. Earlier research on this hormone focused on regulating energy expenditure and glucose homeostasis. Consequently, several studies attempted to characterize the molecule mechanism of Metrnl in glucose metabolism and obesity-related disorders but reported contradictory clinical results. Recent studies gradually noticed its multiple protective functions in inflammatory immune regulations and cardiometabolic diseases, such as inducing macrophage activation, angiogenesis, tissue remodeling, bone formation, and preventing dyslipidemias. A comprehensive understanding of this novel protein is essential to identify its significance as a potential therapeutic drug or a biomarker of certain diseases. In this review, we present the current knowledge on the physiology of Metrnl and its roles in inflammation, immunology, and metabolism, including animal/cell interventional preclinical studies and human clinical studies. We also describe controversies regarding the data of circulation Metrnl in different disease states to determine its clinical application better.
A meta-analysis of chemokines in vitiligo: Recruiting immune cells towards melanocytes
Authors: Speeckaert Reinhart , Belpaire Arno , Speeckaert Marijn M. , van Geel Nanja
Published: February 2023

Chemokine research offers insightful information on the pathogenesis of cutaneous immune disorders, such as vitiligo. Compared to cytokines, the higher detectable levels of chemokines display promising potential as future disease biomarkers. Nonetheless, some published study results are contradictory, which can be attributed to patient characteristics and methodological differences. In this study, a meta-analysis was performed to compare chemokine expression in blood and skin samples from vitiligo patients versus healthy controls. Furthermore, the relationship between chemokine expression and disease activity was evaluated. Chemokine levels were investigated in 15 articles in the circulation and in 9 articles in vitiligo skin. Overall, some clear trends were observed. CXCR3 signaling by CXCL10 and CXCL9 has been confirmed by several reports, although CXCL10 showed more robust findings in blood samples. In this meta-analysis, CCL5, CXCL8, CXCL12, and CXCL16 levels were also significantly elevated. This indicates a complex immune pathway activation in vitiligo that overall supports a Th1-dominant response. Chemokines linked to the Th2 and Th17 pathways were less prevalent. Despite these findings, study protocols that examine a broader range of chemokines are encouraged, because current research is mostly focused on a small number of chemokines that were differentially expressed in previous studies.
NFκB signaling in T cell memory
Authors: Daniels Mark A. , Luera Dezzarae , Teixeiro Emma
Published: February 2023

Memory T cells play an essential role in protecting against infectious diseases and cancer and contribute to autoimmunity and transplant rejection. Understanding how they are generated and maintained in the context of infection or vaccination holds promise to improve current immune-based therapies. At the beginning of any immune response, naïve T cells are activated and differentiate into cells with effector function capabilities. In the context of infection, most of these cells die once the pathogenic antigen has been cleared. Only a few of them persist and differentiate into memory T cells. These memory T cells are essential to host immunity because they are long-lived and can perform effector functions immediately upon re-infection. How a cell becomes a memory T cell and continues being one for months and even years past the initial infection is still not fully understood. Recent reviews have thoroughly discussed the transcriptional, epigenomic, and metabolic mechanisms that govern T cell memory differentiation. Yet much less is known of how signaling pathways that are common circuitries of multiple environmental signals regulate T cell outcome and, precisely, T cell memory. The function of the NFκB signaling system is perhaps best understood in innate cells. Recent findings suggest that NFκB signaling plays an essential and unique role in generating and maintaining CD8 T cell memory. This review aims to summarize these findings and discuss the remaining questions in the field.
Revisiting fall armyworm population movement in the United States and Canada
Authors: Tessnow Ashley E. , Nagoshi Rodney N. , Meagher Robert L. , Fleischer Shelby J.
Published: February 2023

Introduction

Biophysical approaches validated against haplotype and trap catch patterns have modeled the migratory trajectory of fall armyworms at a semi-continental scale, from their natal origins in Texas or Florida through much of the United States east of the Rocky Mountains. However, unexplained variation in the validation analysis was present, and misalignments between the simulated movement patterns of fall armyworm populations and the haplotype ratios at several locations, especially in the northeastern US and Canada, have been reported.

Methods

Using an expanded dataset extending into Canada, we assess the consistency of haplotype patterns that relate overwintered origins of fall armyworm populations to hypothesized dispersal trajectories in North America and compare the geographic distribution of these patterns with previous model projections.

Results and discussion

We confirm the general accuracy of previous modeling efforts, except for late in the season where our data suggests a higher proportion of Texas populations invading the northeast, extending into eastern Canada. We delineate geographic limits to the range of both overwintering populations and show that substantial intermixing of the Texas and Florida migrants routinely occurs north of South Carolina. We discuss annual variation to these migratory trajectories and test the hypothesis that the Appalachian Mountains influence geographic patterns of haplotypes. We discuss how these results may limit gene flow between the Texas and Florida natal populations and limit the hereditary consequences of interbreeding between these populations.
Effects of altitude on the gut microbiome and metabolomics of Sanhe heifers
Authors: Zhang Xinyu , Wang Wei , Cao Zhijun , Yang Hongjian , Wang Yajing , Li Shengli
Published: February 2023

Introduction

Extreme environments at high altitudes pose a significant physiological challenge to animals. We evaluated the gut microbiome and fecal metabolism in Sanhe heifers from different altitudes.

Methods

Twenty Sanhe heifers (body weight: 334.82 ± 13.22 kg, 15-month-old) selected from two regions of China: the Xiertala Cattle Breeding Farm in Hulunbeier, Inner Mongolia [119°57′ E, 47°17′ N; approximately 700 m altitude, low altitude (LA)] and Zhizhao Dairy Cow Farm in Lhasa, Tibet [91°06′ E, 29°36′ N; approximately 3,650 m altitude, high altitude (HA)], were used in this study. Fecal samples were collected and differences in the gut microbiota and metabolomics of Sanhe heifers were determined using 16S rRNA gene sequencing and metabolome analysis.

Results and discussion

The results showed that altitude did not significantly affect the concentrations of fecal volatile fatty acids, including acetate, propionate, butyrate, and total volatile fatty acids (p > 0.05). However, 16S rRNA gene sequencing showed that altitude significantly affected gut microbial composition. Principal coordinate analysis based on Bray–Curtis dissimilarity analysis revealed a significant difference between the two groups (p = 0.001). At the family level, the relative abundances of Peptostreptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Family_XIII were significantly lower (p < 0.05) in LA heifers than in HA heifers. In addition, the relative abundances of Lachnospiraceae, Domibacillus, Bacteroidales_S24-7_group, Bacteroidales_RF16_group, Porphyromonadaceae, and Spirochaetaceae were significantly higher in HA heifers than in LA heifers (p < 0.05). Metabolomic analysis revealed the enrichment of 10 metabolic pathways, including organismal systems, metabolism, environmental information processing, genetic information processing, and disease induction. The genera Romboutsia, Paeniclostridium, and g_unclassified_f_Lachnospiraceae were strongly associated with the 28 differential metabolites. This study is the first to analyze the differences in the gut microbiome and metabolome of Sanhe heifers reared at different altitudes and provides insights into the adaptation mechanism of Sanhe heifers to high-altitude areas.
Transcriptome, intestinal microbiome and histomorphology profiling of differences in the response of Chinese sea bass (Lateolabrax maculatus) to Aeromonas hydrophila infection
Authors: Pan Chao , Zhu Yanran , Cao Kaixin , Li Juexian , Wang Siyu , Zhu Jiahua , Zeng Xiaoman , Zhang Heqian , Qin Zhiwei
Published: February 2023

The Chinese sea bass (Lateolabrax maculatus) is an important aquaculture fish, but diseases caused by Aeromonas hydrophila have led to severe economic losses to the aquaculture industry in recent years. To date, only a few studies have focused on the relationship between the intestinal immune response and changes in intestinal microbes by A. hydrophila infection. Here, we report the transcriptome and intestinal changes in infected sea bass. Histopathological results showed that severe steatosis and vacuolation occurred in the liver and that the intestinal villi and mesentery were seriously affected after infection. By extracting total RNA from intestinal tissue and studying the transcriptome profile, 1,678 genes (1,013 upregulated and 665 downregulated) were identified as significantly differentially expressed genes (DEGs). These genes are involved in many immune-related signalling pathways, such as the NOD-like receptor, C-type lectin receptor, and Toll-like receptor signalling pathways. Moreover, the intestinal microbes of sea bass changed significantly after infection. Interestingly, at the genus level, there was an increase in Serratia, Candida arthromitus and Faecalibacterium as well as a decrease in Akkermansia and Parabacteroides after infection. The results also indicated that some of the DEGs involved in the immune response were related to the genus level of intestinal microbiota. Finally, there was a relationship between gene expression patterns and the bacterial structure in the host intestine. Our study provides a reference for the study of the immune response and particular functions of intestinal microbes of sea bass after pathogen infection.