bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism
Authors: Miglietta Francesca , Iamartino Luca , Palmini Gaia , Giusti Francesca , Marini Francesca , Iantomasi Teresa , Brandi Maria Luisa
Published: January 2023

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long term patient survival, a growing incidence of late HSCT-related sequelae has been reported, being variably associated with negative effects on quality of life of patients and having a non-negligible impact on healthcare systems. The most predominantly observed HSCT-caused complications are chronic alterations of the endocrine system and metabolism, which endanger post-operative quality of life and increase morbidity and mortality of transplanted patients. Here, we specifically review the current knowledge on HSCT-derived side-effects on the perturbation of mineral metabolism; in particular, the homeostasis of calcium, focusing on current reports regarding osteoporosis and recurrent renal dysfunctions that have been observed in a percentage of HSC-transplanted patients. Possible secondary implications of conditioning treatments for HSCT on the physiology of the parathyroid glands and calcium homeostasis, alone or in association with HSCT-caused renal and bone defects, are critically discussed as well.
Endoplasmic reticulum stress associates with the development of intervertebral disc degeneration
Authors: Huang Jishang , Zhou Qingluo , Ren Qun , Luo Liliang , Ji Guanglin , Zheng Tiansheng
Published: January 2023

Endoplasmic reticulum (ER) is an important player in various intracellular signaling pathways that regulate cellular functions in many diseases. Intervertebral disc degeneration (IDD), an age-related degenerative disease, is one of the main clinical causes of low back pain. Although the pathological development of IDD is far from being fully elucidated, many studies have been shown that ER stress (ERS) is involved in IDD development and regulates various processes, such as inflammation, cellular senescence and apoptosis, excessive mechanical loading, metabolic disturbances, oxidative stress, calcium homeostasis imbalance, and extracellular matrix (ECM) dysregulation. This review summarizes the formation of ERS and the potential link between ERS and IDD development. ERS can be a promising new therapeutic target for the clinical management of IDD.
Comprehensive analysis of the effect of Hashimoto’s thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in papillary thyroid cancer
Authors: Tan Hai-Long , Nyarko AdolphusOsei , Duan Sai-li , Zhao Ya-Xin , Chen Pei , He Qiao , Zhang Zhe-Jia , Chang Shi , Huang Peng
Published: January 2023

Purpose

Hashimoto’s thyroiditis often leads to reactive hyperplasia of the central compartment lymph nodes in papillary thyroid carcinoma (PTC) patients. However, the effect and clinical significance of Hashimoto’s thyroiditis (HT) on ultrasonography evaluation for cervical lymph node (LN) lesions remain unknown. This study aims to investigate the effect of Hashimoto’s thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in PTC patients.

Patients and methods

This study consecutively enrolled 1,874 PTC patients who underwent total thyroidectomy and radical cervical lymph node dissection between January 2010 and December 2021. Eligible patients were categorized as with HT and without HT. The diagnostic performance of preoperative ultrasonography for cervical LN lesions (including central LNs and lateral LNs) was evaluated between PTC patients with HT and those without HT, respectively.

Results

Among the 1,874 PTC patients, 790 (42.1%) had central cN+ and 1,610 (85.9%) had lateral cN+. Compared with PTC patients without HT, the preoperative US for central LNs displays a higher false-positive rate (27.9% vs. 12.2%, p <0.001) and a lower specificity (72.1% vs. 87.8%, p < 0.001) in PTC patients with HT. Moreover, in PTC patients with HT, the ratio of the absence of fatty hilum in central LNs without metastasis was higher than in PTC patients without HT (13.02% vs. 7.46%, p = 0.013). However, no such differences were observed in lateral LNs.

Conclusion

HT will interfere with the preoperative US evaluation for central LNs and increase the incidence of the absence of fatty hilum in central benign LNs. When PTC patients have concomitant HT, clinicians should thoroughly evaluate the central LNs, thereby decreasing the incidence of misdiagnosis and unnecessary surgery.
Optimal allocation of phase shifting transformer with uncertain wind power based on dynamic programming
Authors: Fu Kang , Du Zhaobin , Li Feng , Li Zuohong , Xia Chengjun
Published: January 2023

Phase Shifting Transformer (PST) can help improve the power flow distribution of the transmission section, which can increase the wind power consumption of the grid. In order to adapt the PST allocation to the grid evolution, this paper presents a dynamic programming method to allocate PST in each planning stage of the grid optimally. The optimal allocation model of PST under a single grid seeks to maximize the wind power consumption and the Total Transfer Capacity (TTC) between areas. A calculation method for TTC of grids containing PST and wind power is proposed. The Non-Dominated Sorting Genetic Algorithm II (NSGA2) is used to solve the Pareto sets under each planning stage of the grid. Then, the optimal planning path of PST is derived based on dynamic programming. The superiority of the proposed method is demonstrated by comparing the IEEE-118 system results of dynamic and static programming.
Islanding detection method for microgrids based on CatBoost
Authors: Chen Ran , Zhou Li , Xiong Chuanyu , Xu Hanping , Zhang Zhaoyang , He Xuhui , Dong Qingguo , Wang Can
Published: January 2023

The occurrence of unintentional islanding will seriously threaten the stable operation of a microgrid (MG). Therefore, detecting the islanding of an microgrid timely is an important premise to ensure the microgrid operates safely and stably. However, the problem of dead zone exists in the traditional islanding detection process because the threshold of various electrical feature quantities of the point of common coupling (PCC) cannot be determined effectively. To solve this problem, an islanding detection method based on CatBoost is proposed for an microgrid. The novelty of this method lies in two aspects: 1) To reduce the error brought by the electrical feature quantities with weak correlation in the process of islanding detection, an analysis method based on the Spearman correlation coefficient is used to extract the electrical feature quantities closely related to islanding detection. 2) To determine the threshold of the electrical feature quantities more accurately and reduce the dead zone of island detection, an integrated learning machine is used to dig out correlations between the electrical feature quantities and the operation of an microgrid. The performance of the proposed islanding detection method is verified based on the modified IEEE13-bus system. The results of the example verify that the proposed islanding detection can achieve higher detection accuracy in cases of grid-connected interference and line faults.
Adoption impact of solar based irrigation facility by water-scarce northwestern areas farmers in Bangladesh: Evidence from panel data analysis
Authors: Sunny Faruque As , Islam Mohammad Ariful , Karimanzira Taonarufaro Tinaye Pemberai , Lan Juping , Rahman Md Sadique , Zuhui Huang
Published: January 2023

Introduction: Fossil fuel and electricity-based irrigation practices contribute to greenhouse gases and add substantial costs to water access. Solar-powered irrigation is spreading globally, notably in developing countries, as a solution to the rising energy and climate concerns related to agriculture. This policy perspective devoted to examining the impact of the solar irrigation facilities (SIF) adoption on irrigation cost and return on investment (ROI) based on seven years of panel data seeks to contribute to the efforts to propel solar irrigation toward delivering on the myriad of promises.

Methods: Panel logistic regression was employed to analyze adoption determinants, while adoption impact was evaluated through the propensity score matching with the difference-in-difference (PSM-DID) method. In addition, the time and panel fixed effect DID and doubly robust DID model was also used for robustness check.

Results: The result reveals that SIF adoption significantly increased ROI by 20% to 30% and reduced irrigation costs by 21% to 30%.

Conclusion: The findings call for further research and analysis on evidence-based best practices for solar irrigation solutions at the farm level so that the dissemination of this revolutionary technology, apart from contributing to the advancement of the energy sector, also plays a vital role in driving us towards establishing a more equitable and sustainable world.
Research on construction schedule risk management of power supply and distribution projects based on MCS-AHP model
Authors: Xinfa Tang , Tian Zhong , Xingwu Huang , Dan Li
Published: January 2023

In order to manage the construction schedule risk of power supply and distribution engineering, a construction schedule risk evaluation model, namely the Monte Carlo simulation method - Analytic Hierarchy Process (MCS-AHP) model, is proposed. In this model, the Monte Carlo simulation method is adopted to improve the analytic Hierarchy Process (AHP), and the normal distribution interval is used to replace the specific value when constructing the fuzzy complementary judgment matrix, to reduce the risk of fuzzy thinking and incomplete information or scattered data in the process of investigation and judgment and improve the scientific evaluation. This paper takes a power supply and distribution project in Guangdong Province as an example uses the MCS-AHP model to measure the key factors limiting the project progress, and uses the AHP method for comparative analysis, to verify the feasibility of the MCS-AHP model. The analysis shows that the key influencing factors are material and equipment procurement, production and arrival, installation of 10 kv high voltage switchboard, electrical acceptance and single machine commissioning, installation of low-voltage switchboard and DC switchboard, and foundation construction of power station equipment, etc., which are consistent with the actual situation. Therefore, it is feasible to construct the MCS-AHP model, which can provide a new way of thinking for schedule risk management analysis.
Reliability analysis and reliable operation of three-level ANPC inverter
Authors: Zheng Xiaolin , Huang Xiaoxiao , Chen Peiyu , Chong Zhiqiang , Yuan Zhongchen
Published: January 2023

The three-level active neutral-point-clamped (3L-ANPC) inverters have been widely used in medium-voltage high-power electrical drives. The purpose of this paper is to achieve the reliable operation for 3L-ANPC inverters by reliability analysis and optimal switching and control strategies, while the performance of output waveforms of inverters is maintained. This paper starts by analyzing the power loss and the reliability of power semiconductor devices. On this basis, a mathematical model is derived for online condition monitoring of semiconductor devices. Then, the modulation strategies of the passive commutation mode and the active commutation mode are designed for the 3L-ANPC inverter, and the power loss distributions are analyzed among different semiconductor devices accordingly. Finally, three optimized strategies are designed to improve the reliability of the 3L-ANPC inverter under different load conditions based on different commutation modes and the developed reliability model. Both the simulation using MATLAB Simulink as well as PLECS have been conducted to verify the validity of analysis and control for improving reliability of 3L-ANPC inverters in this paper.
Configuration research on innovation performance of digital enterprises: Based on an open innovation and knowledge perspective
Authors: Dong Hao , Guo Ju’e , Chen Tianqing , Murong Ruiyi
Published: January 2023

This paper takes 36 unicorn enterprises in China as a sample case. Based on the perspective of open innovation and knowledge, combined with the background of the transformation and development of China’s digital economy, the antecedent conditions such as the three dimensions of knowledge integration ability, the two dimensions of open innovation and knowledge sharing are integrated by using configuration thinking and fuzzy set qualitative comparative analysis (fsQCA) method. The multiple concurrent factors and causal complex mechanisms affecting innovation performance are discussed. The results show that: 1) The different dimensions of knowledge integration capability, open innovation, and knowledge sharing have six configurations to achieve high-level firm performance; 2) Different knowledge integration capabilities can all promote innovation performance; 3) knowledge sharing improves the management and utilization of knowledge, which is an important guarantee for improving innovation performance. The conclusion expands the innovation perspective of the matching of knowledge and open innovation, helps to understand the mechanism of innovation performance, and provides theoretical reference and beneficial enlightenment for enterprises to effectively improve innovation performance.
Evolution and prediction of land use around metro stations
Authors: Fu Fei , Jia Xia , Wu Dan , Zhao Qiuji , Fang Han , Lin Liwei , Aye Lu
Published: January 2023

Metro stations are considered high-quality resources for promoting urban development, which have great influences on the surrounding land use changes. The simulation and prediction of land use change can provide a scientific basis for urban land planning. In this work, the cellular automata (CA)-Markov model was adopted by taking into account point of interest (POI) kernel density and station accessibility as driving factors to predict the land use change of station surrounding areas. Then, the land type compositions of different years, temporal and spatial evolution of landscape patterns, and strategies of different metro stations were explored. The results show that the Kappa coefficients of the Zoo Station and the Lu Xiao Station are 87% and 79%, respectively, indicating that the improved CA-Markov model can predict land use changes more accurately by considering POI kernel density and station accessibility. Finally, different optimized strategies based on systematic predictions of land use landscape patterns according to the spatial and temporal distribution of metro stations were proposed. The work provides important references for predicting the impact of new metro stations on land use in the future and guides the adjustment and optimization of land use policy planning.
Leukoencephalopathy hypomyelination with brainstem and spinal cord involvement and leg spasticity caused by DARS1 mutations
Authors: Zhu Jingyi , Guo Xiaomin , Ran Ningjing , Liang Jingtao , Liu Fuyou , Liu Junyan , Wang Rongyu , Jiang Lianyan , Yang Dongdong , Liu Meijun
Published: January 2023

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), caused by aspartyl-tRNA synthetase (DARS1) gene mutations, is extremely rare, with only a few cases reported worldwide; thus, reports on HBSL treatment are few. In this review, we summarized the clinical manifestations, imaging features, treatment methods, and gene mutations responsible for HBSL based on relevant studies and cases.
Identification of genes involved in chicken follicle selection by ONT sequencing on granulosa cells
Authors: Li Dandan , Zhong Conghao , Sun Yi , Kang Li , Jiang Yunliang
Published: January 2023

In chickens, follicle selection is an important process affecting laying traits, which is characterized by the differentiation of granulosa cells and the synthesis of progesterone by granulosa cells from hierarchical follicles. By using Oxford Nanopore Technologies (ONT) approach, we compared the transcriptomes of granulosa cells between pre-hierarchical (Pre-GCs) and hierarchical follicles (Post-GCs) to identify genes underlying chicken follicle selection. A total of 2,436 differentially expressed genes (DEGs), 3,852 differentially expressed transcripts (DETs) and 925 differentially expressed lncRNA transcripts were identified between chicken Pre-GCs and Post-GCs. For all of the significant DETs, the alternative 3′splice sites (A3) accounted for a maximum of 23.74% of all alternative splicing events. Three DETs of the 7-dehydrocholesterol reductase gene (DHCR7) named as T1, T3, and T4, differing in 5′untranslated regions (UTRs), increased in Post-GCs with different folds (T1: 1.83, T3: 2.42, T4: 5.06). The expression of the three DHCR7 transcripts was upregulated by estrogen in a dose-dependent manner, while was downregulated by bone morphogenetic protein 15 (BMP15) and transforming growth factor-beta 1 (TGF-β1). Follicle-stimulating hormone (FSH) and bone morphogenetic protein 4 (BMP4) promoted the expression of the three DHCR7 transcripts in Pre-GCs at lower concentrations, while repressed their expression at higher concentrations. The data from this study may provide a reference for better understanding of the genetic mechanisms underlying follicle selection in chicken and other poultry species.
Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer
Authors: Lothion-Roy Jennifer , Haigh Daisy B. , Harris Anna E. , Metzler Veronika M. , Alsaleem Mansour , Toss Michael S. , Kariri Yousif , Ntekim Atara , Robinson Brian D. , Khani Francesca , Gudas Lorraine J. , Allegrucci Cinzia , James Victoria H. , Madhusudan Srinivasan , Mather Melissa , Emes Richard D. , Archer Nathan , Fray Rupert G. , Rakha Emad , Jeyapalan Jennie N. , Rutland Catrin S. , Mongan Nigel P. , Woodcock Corinne L.
Published: January 2023

N6-methyladenosine (m6A) is the most abundant internal mRNA modification and is dynamically regulated through distinct protein complexes that methylate, demethylate, and/or interpret the m6A modification. These proteins, and the m6A modification, are involved in the regulation of gene expression, RNA stability, splicing and translation. Given its role in these crucial processes, m6A has been implicated in many diseases, including in cancer development and progression. Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in men and recent studies support a role for m6A in PCa. Despite this, the literature currently lacks an integrated analysis of the expression of key components of the m6A RNA methyltransferase complex, both in PCa patients and in well-established cell line models. For this reason, this study used immunohistochemistry and functional studies to investigate the mechanistic and clinical significance of the METTL3, METTL14, WTAP and CBLL1 components of the m6A methyltransferase complex in PCa specimens and cell lines. Expression of METTL3 and CBLL1, but not METTL14 and WTAP, was associated with poorer PCa patient outcomes. Expression of METTL3, METTL14, WTAP and CBLL1 was higher in PCa cells compared with non-malignant prostate cells, with the highest expression seen in castrate-sensitive, androgen-responsive PCa cells. Moreover, in PCa cell lines, expression of METTL3 and WTAP was found to be androgen-regulated. To investigate the mechanistic role(s) of the m6A methyltransferase complex in PCa cells, short hairpin RNA (shRNA)-mediated knockdown coupled with next generation sequencing was used to determine the transcriptome-wide roles of METTL3, the catalytic subunit of the m6A methyltransferase complex. Functional depletion of METTL3 resulted in upregulation of the androgen receptor (AR), together with 134 AR-regulated genes. METTL3 knockdown also resulted in altered splicing, and enrichment of cell cycle, DNA repair and metabolic pathways. Collectively, this study identified the functional and clinical significance of four essential m6A complex components in PCa patient specimens and cell lines for the first time. Further studies are now warranted to determine the potential therapeutic relevance of METTL3 inhibitors in development to treat leukaemia to benefit patients with PCa.
Age-related changes in antigen-specific natural antibodies are influenced by sex
Authors: Webster Sarah E. , Tsuji Naomi L. , Clemente Michael J. , Holodick Nichol E.
Published: January 2023

Introduction

Natural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis. CD5+ B-1 cell-derived NAbs have a unique germline-like structure that lacks N-additions, a feature critical for providing protection against infection. Previously, we demonstrated the repertoire and germline status of PtC+CD5+ B-1 cell IgM obtained from male mice changes with age depending on the anatomical location of the B-1 cells. More recently, we demonstrated serum antibody from aged female mice maintains protection against pneumococcal infection, whereas serum antibody from male mice does not provide protection.

Results

Here, we show that aged female mice have significantly more splenic PtC+CD5+ B-1 cells and more PtC specific serum IgM than aged male mice. Furthermore, we find both age and biological sex related repertoire differences when comparing B cell receptor (BCR) sequencing results of PtC+CD5+ B-1 cells. While BCR germline status of PtC+CD5+ B-1 cells from aged male and female mice is similar in the peritoneal cavity, it differs significantly in the spleen, where aged females retain germline configuration and aged males do not. Nucleic acid sensing toll-like receptors are critical in the maintenance of PtC+ B-1 cells; therefore, to begin to understand the mechanism of differences observed between the male and female PtC+CD5+ B-1 cell repertoire, we analyzed levels of cell-free nucleic acids and found increases in aged females.

Conclusion

Our results suggest the antigenic milieu differs between aged males and females, leading to differential selection of antigen-specific B-1 cells over time. Further elucidation of how biological sex differences influence the maintenance of B-1 cells within the aging environment will be essential to understand sex and age-related disparities in the susceptibility to bacterial infection and will aid in the development of more effective vaccination and/or therapeutic strategies specific for males and females.
Integrated analysis of transcription factor-mRNA-miRNA regulatory network related to immune characteristics in medullary thyroid carcinoma
Authors: Weng Danfeng , He Long , Chen Xiangna , Lin Huangfeng , Ji Daihan , Lu Shuting , Ao Lu , Wang Shenglin
Published: January 2023

Background

Medullary thyroid carcinoma (MTC), a thyroid C cell-derived malignancy, is poorly differentiated and more aggressive than papillary, follicular and oncocytic types of thyroid cancer. The current therapeutic options are limited, with a third of population suffering resistance. The differential gene expression pattern among thyroid cancer subtypes remains unclear. This study intended to explore the exclusive gene profile of MTC and construct a comprehensive regulatory network via integrated analysis, to uncover the potential key biomarkers.

Methods

Multiple datasets of thyroid and other neuroendocrine tumors were obtained from GEO and TCGA databases. Differentially expressed genes (DEGs) specific in MTC were identified to construct a transcription factor (TF)-mRNA-miRNA network. The impact of the TF-mRNA-miRNA network on tumor immune characteristics and patient survival was further explored by single-sample GSEA (ssGSEA) and ESTIMATE algorithms, as well as univariate combined with multivariate analyses. RT-qPCR, cell viability and apoptosis assays were performed for in vitro validation.

Results

We identified 81 genes upregulated and 22 downregulated in MTC but not in other types of thyroid tumor compared to the normal thyroid tissue. According to the L1000CDS2 database, potential targeting drugs were found to reverse the expressions of DEGs, with panobinostat (S1030) validated effective for tumor repression in MTC by in vitro experiments. The 103 DEGs exclusively seen in MTC were involved in signal release, muscle contraction, pathways of neurodegeneration diseases, neurotransmitter activity and related amino acid metabolism, and cAMP pathway. Based on the identified 15 hub genes, a TF-mRNA-miRNA linear network, as well as REST-cored coherent feed-forward loop networks, namely REST-KIF5C-miR-223 and REST-CDK5R2-miR-130a were constructed via online prediction and validation by public datasets and our cohort. Hub-gene, TF and miRNA scores in the TF-mRNA-miRNA network were related to immune score, immune cell infiltration and immunotherapeutic molecules in MTC as well as in neuroendocrine tumor of lung and neuroblastoma. Additionally, a high hub-gene score or a low miRNA score indicated good prognoses of neuroendocrine tumors.

Conclusion

The present study uncovers underlying molecular mechanisms and potential immunotherapy-related targets for the pathogenesis and drug discovery of MTC.
Sinonasal diffuse large B-cell lymphoma in a patient with Wiskott–Aldrich syndrome: A case report and literature review
Authors: Sun Xiwen , Luo Chunyu , Tang Ru , Mao Song , Zhu Ying , Fei Chonghui , Wang Mengyu , Tan Shaolin , Zhang Shiyao , Zhou Jiayao , Lin Hai , Li Zhipeng , Zhang Weitian
Published: January 2023

Wiskott–Aldrich syndrome (WAS) is a rare primary immunodeficiency disease with a predisposition towards autoimmunity and lymphoproliferative diseases. Non-Hodgkin lymphoma (NHL) is reported to be the predominant form of malignant tumor in WAS sufferers. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of NHL while it is uncommon to occur in paranasal sinuses and especially when associated with WAS. In this article, we report a unique case of WAS associated with DLBCL in paranasal sinuses and review the major publications of WAS-related lymphomas that occurred in the head and neck area. This study extends the available therapies for WAS-related lymphomas and emphasizes the significance of recognition for sinonasal lymphomas in WAS patients presenting with sinusitis.
Human and mouse TLR2 results in different activation of p38 and JNK signal pathway in HaCaT infected by Trichophyton rubrum and Microsporum canis
Authors: Su Zhen , Deng Weiwei , Zhan Shuting , Li Meirong , Yin Songchao , Chen Jian
Published: January 2023

Introduction

It has long been recognized that inflammation to dermatophyte infection is different among various hosts, but the mechanism underlying is still not well understood. Toll-like receptor (TLR2), mediates the innate immune response against dermatophyte infection and is very important to trigger the inflammatory response to dermatophytes. Considering the different amino acid sequences and structures of TLR2, we speculated that TLR2 from different hosts will activate the downstream signal pathways to varying degrees, resulting in different inflammatory responses to dermatophytes.

Methods

In this study, we constructed the mice-human fusion TLR2 expressed HaCaT (mhTLR2-HaCaT) by replacing the extracellular ligand recognition region of human TLR2 with that of the mouse. Then hTLR2-HaCaT cells and mhTLR2-HaCaT cells were infected with T. rubrum and M. canis for 24 h followed by immunoblotting to asses associated proteins of p38 and JNK signal pathway.

Results

Compared with that of human TLR2 expressed HaCaT (hTLR2-HaCaT), levels of phosphorylated p38 protein were increased in mhTLR2-HaCaT cells stimulated by T. rubrum for 24 h, and levels of phosphorylatedJNK and c-Jun protein were increased in mhTLR2-HaCaT cells whenstimulated with M. canis for 24 h.

Discussion

Compared with hTLR2-HaCaT cells, p38 and JNK signal pathwayswere activated in mhTLR2-HaCaT after being infected by Trichophyton rubrumand Microsporum canis, respectively. Since p38 and JNK are the mainpathways that transduce the signal for host recognition of dermatophytes andmediate the downstream inflammatory response, it suggested that theinterspecific difference of TLR2 ectodomain may be one of the reasons for thedifferent inflammatory manifestations between humans and mice infected bythese two dermatophytes. Quite especially, the mouse-derived TLR2extracellular recognition region is more effective in recognizing T. rubrum andM. canis to activate the downstream signal pathways, resulting in a tenserinflammatory response against these two dermatophytes.
Identification of EMT-related alternative splicing event of TMC7 to promote invasion and migration of pancreatic cancer
Authors: Weng Yuanchi , Qian Hao , Hong Liwen , Zhao Shulin , Deng Xiaxing , Shen Baiyong
Published: January 2023

Objective

Epithelial-to-mesenchymal transition (EMT) is tightly associated with the invasion and metastasis of pancreatic cancer with rapid progression and poor prognosis. Notably, gene alternative splicing (AS) event plays a critical role in regulating the progression of pancreatic cancer. Therefore, this study aims to identify the EMT-related AS event in pancreatic cancer.

Methods

The EMT-related gene sets, transcriptomes, and matched clinical data were obtained from the MSigDB, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. Key gene AS events associated with liver metastasis were identified by prognostic analysis, gene set variation analysis (GSVA), and correlation analysis in pancreatic cancer. The cell line and organoid model was constructed to evaluate these key gene AS events in regulating pancreatic cancer in vitro. Furthermore, we established an EMT-related gene set consisting of 13 genes by prognostic analysis, the role of which was validated in two other databases. Finally, the human pancreatic cancer tissue and organoid model was used to evaluate the correlation between the enrichment of this gene set and liver metastasis.

Results

Prognostic analysis and correlation analysis revealed that eight AS events were closely associated with the prognosis of pancreatic cancer. Furthermore, the expression of TMC7 and CHECK1 AS events was increased in the metastatic lesions of the human tissue and organoid model. Additionally, the knockdown of exon 17 of TMC7 significantly inhibited the proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments. Finally, the expression of exon 17 of TMC17 exhibited a significant correlation with the poor prognosis in pancreatic ductal adenocarcinoma (PDAC).

Conclusion

The AS events of TMC7 and CHECK1 were associated with liver metastasis in pancreatic cancer. Moreover, exon 17 of TMC7 could be a potential therapeutic target in pancreatic cancer.
Research progress on circular RNA vaccines
Authors: Bai Yu , Liu Dong , He Qian , Liu Jianyang , Mao Qunying , Liang Zhenglun
Published: January 2023

Owing to the success of linear mRNA coronavirus disease 2019 (COVID-19) vaccines, biopharmaceutical companies and research teams worldwide have attempted to develop more stable circular RNA (circRNA) vaccines and have achieved some preliminary results. This review aims to summarize key findings and important progress made in circRNA research, the in vivo metabolism and biological functions of circRNAs, and research progress and production process of circRNA vaccines. Further, considerations regarding the quality control of circRNA vaccines are highlighted herein, and the main challenges and problem-solving strategies in circRNA vaccine development and quality control are outlined to provide a reference for circRNA vaccine-related research.
Review: The role of HMGB1 in spinal cord injury
Authors: Mo Yizhang , Chen Kebing
Published: January 2023

High mobility group box 1 (HMGB1) has dual functions as a nonhistone nucleoprotein and an extracellular inflammatory cytokine. In the resting state, HMGB1 is mainly located in the nucleus and regulates key nuclear activities. After spinal cord injury, HMGB1 is rapidly expressed by neurons, microglia and ependymal cells, and it is either actively or passively released into the extracellular matrix and blood circulation; furthermore, it also participates in the pathophysiological process of spinal cord injury. HMGB1 can regulate the activation of M1 microglia, exacerbate the inflammatory response, and regulate the expression of inflammatory factors through Rage and TLR2/4, resulting in neuronal death. However, some studies have shown that HMGB1 is beneficial for the survival, regeneration and differentiation of neurons and that it promotes the recovery of motor function. This article reviews the specific timing of secretion and translocation, the release mechanism and the role of HMGB1 in spinal cord injury. Furthermore, the role and mechanism of HMGB1 in spinal cord injury and, the challenges that still need to be addressed are identified, and this work will provide a basis for future studies.
A gulf-wide synoptic isoscape of zooplankton isotope ratios reveals the importance of nitrogen fixation in supporting secondary production in the central Gulf of Mexico
Authors: Hernández-Sánchez Oscar Gabriel , Camacho-Ibar Víctor F. , Barbero Leticia , Herguera Juan Carlos , Herzka Sharon Z.
Published: January 2023

A synoptic gulf-wide isoscape of carbon (δ13C) and nitrogen (δ15N) in the Gulf of Mexico based on mesozooplankton (335-1000 um) was used as a proxy for the isotopic baseline and for calculating regional contributions of dissolved inorganic nitrogen sources. Mesozooplankton were sampled at 0-200 m (depth permitting) during the XIXIMI-06 and GOMECC-3 cruises held during the summer of 2017. A striking latitudinal gradient was found in δ15N values of zooplankton, with the highest values (10.4 ± 1.2‰) found over the northern shelf, and lowest values in the central, oligotrophic gulf (1.9 ± 0.5‰). To estimate the fractional contribution of potential nitrogen sources, the gulf was divided into six regions based on the spatial distribution of surface Chl-a, SST from remote sensing products and likely region-specific source contributions. A literature survey of (δ13C and δ15N values of particulate organic matter was used to characterize region-specific endpoint isotope ratios for use in a Bayesian isotope mixing model. Regional differences in δ15N values and the results of mixing models indicated nitrogen fixation is most likely an important source (45-74% contribution) of new nitrogen in the oceanic regions of the Gulf, the Loop Current and the Yucatan Shelf. In the oligotrophic gulf, the potential input of relatively light nitrate that reflects remineralization of surface layer POM or the excretion of light nitrogen by heterotrophs was insufficient to explain the low δ15N values found in the central Gulf, although it could account for about 40% of the N supporting secondary production. The high nitrogen isotope ratios found in the northern shelf were attributed to denitrified N (60%) and the inflow of heavy nitrogen from the Mississippi-Atchafalaya river system. Our results support the potential importance of fixed nitrogen in the deep waters of the Gulf of Mexico during the summer, characteristic for its highly stratified surface waters.
Reflecting on the importance of open communication and social capital for the co-creation of knowledge in Irish fisheries
Authors: Calderwood Julia , Pedreschi Debbi , Ó Cuaig Macdara , Reid David G.
Published: January 2023

Fishing industry stakeholders have unique and important contributions to make to fisheries research. Co-operative and collaborative research approaches between science and industry are important to facilitate the documentation of fishers’ knowledge and the co-creation of common understandings. Successful collaborations require open communication, trust and social capital, but numerous barriers exist to establishing these effective partnerships. This paper takes a narrative approach to reflect on the authors’ experiences of engaging and collaborating with Irish fishers in the quest for the co-creation of knowledge, while considering how data from industry can best be used and integrated into scientific processes. This includes reflecting on barriers faced, in addition to motives and opportunities that have enabled this work to progress. Through case study examples, we reflect on issues surrounding misunderstandings regarding the roles of scientists and the scientific process, a lack of transparency, a lack of trust, historical/legacy issues, and contemporary pressures including the COVID-19 pandemic and impacts of Brexit. Building trust and active communication are identified as key elements to effectively co-create knowledge and common understanding. Trust is often developed in an informal setting, but more formalized processes, increased transparency and opportunities to engage, and institutional supports may further facilitate effective knowledge co-creation in fisheries.
Labile and refractory fractions of sedimentary organic carbon off the Changjiang Estuary and its implications for sedimentary oxygen consumption
Authors: Cao Yu , Huang Hong , Zhao Xu , Li Jun , Wang Teng , Lin Jun , Zhu Zhuo-Yi
Published: January 2023

Estuarine and coastal area is dynamic zone for both marine carbon and oxygen cycles. There is limited evaluation of the labile and refractory fraction of sedimentary organic carbon and further a lack of attention to the corresponding potential in dissolved oxygen utilization. In this study, we collected sediment samples from the Changjiang estuary and adjacent coastal areas in the East China Sea in June 2019 to reveal the distribution, main controlling factor, and implications of four operational fractions of sediment organic carbon that range from labile to refraction. In the laboratory, we processed and defined the four operational fractions of sedimentary organic carbon, includes 1) pure water extractable carbon (WEC), 2) salt (K2SO4 solution) extractable carbon (SEC), 3) Microbial biomass carbon (MBC; chloroform extractable carbon), and 4) refractory organic carbon (ROC; the acid-processed fraction). We revealed that off the Changjiang Estuary, the bulk sedimentary organic carbon (SOC), WEC, SEC, MBC, and ROC were 9.43 ± 3.07 g/kg, 0.12 ± 0.10 g/kg, 0.16 ± 0.07 g/kg, 1.58 ± 0.45 g/kg, and 4.38 ± 1.95 g/kg, respectively. Sediment grain size played a vital role in constraining the LOC fractions, and samples from aquaculture areas showed extra-higher levels of LOC when compared to samples from the non-aquaculture area. The LOC and MBC fraction showed clear negative relation with dissolved oxygen (DO) in the near bottom waters under high DO background (DO > 5.5 mg/L), whereas in a low DO background (DO < 3-4 mg/L) no clear relation can be found. Based on our observed LOC content and DO concentration in the near bottom waters, the depth of hypoxia in the near bottom waters, which would be caused by a total decomposition of 4 mm of LOC in the top sediment, ranged between 0.3 m to 4.7 m with an average depth of 2 m. This value (2 m) means that sedimentary oxygen consumption would contribute 10% in the occurrence of hypoxia, with the rest contributing from water column respiration. Overall, we used the LOC fraction of sedimentary organic carbon to address the dissolved oxygen consumption in the near bottom waters and further study is needed to evaluate this approach.
A novel approach to estimate power demand of auxiliary engine loads of light duty vehicles
Authors: Gajanayake Surath , Bandara Saman , Sugathapala Thusitha
Published: January 2023

On par with rapid motorization, excessive energy demand and air pollution have become major challenges in the global context. Fuel economy programs and emission reduction targets have proven to be among the most effective in mitigating these issues. In developing successful fuel economy programs and policies, understanding the factors affecting the fuel consumption of road vehicles is essential. Auxiliary engine loads are one of the commonest factors affecting a vehicle’s fuel economy performance. An auxiliary engine load is defined as the energy utilized to operate auxiliary equipment that draws its power from the vehicle’s engine. This study was limited to light duty vehicles, and an analytical method was adopted to assess the fuel economy impact of the auxiliary equipment in terms of air-conditioning load, alternator load, and water pump and steering pump load. As one of the main deliverables, the study developed a novel approach for estimating and modeling the air-conditioning load which is the major auxiliary energy consumer. For an average car of 100 brake horsepower (bhp) (74.7 kW), the engine auxiliary equipment consumes approximately 13.130 kW of power at an engine operating speed of 3,000 RPM, which amounts to 17.6% of the total bhp output. The major contributors to engine power demand are the air-conditioning unit and the alternator, which account for over 97% of the total auxiliary power requirement, while the water-pump and power steering-pump use relatively little power at 3% of the total auxiliary power demand. The novelty of the method adopted during this study is that it theoretically determines the major contributor of the auxiliary power demand, the air-conditioning load, whereas prior reports have used approaches involving empirical methods.
Structure-based pharmacophore modeling, virtual screening, and molecular dynamics simulation studies for identification of Plasmodium falciparum 5-aminolevulinate synthase inhibitors
Authors: Oduselu Gbolahan O. , Afolabi Rufus , Ademuwagun Ibitayo , Vaughan Ashley , Adebiyi Ezekiel
Published: January 2023

Plasmodium falciparum (Pf) 5-aminolevulinic acid synthase (5-ALAS) is an essential enzyme with high selectivity during liver stage development, signifying its potential as a prophylactic antimalarial drug target. The aim of this study was to identify important potential lead compounds which can serve as inhibitors of Pf 5-ALAS using pharmacophore modeling, virtual screening, qualitative structural assessment, in silico ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluation and molecular dynamics simulation. The best model of the tertiary structure of Pf 5-ALAS was obtained using MolProbity, while the following databases were explored for the pharmacophore-based virtual screening: CHEMBL, ChemDiv, ChemSpace, MCULE, MCULE-ULTIMATE, MolPort, NCI Open Chemical Repository, LabNetwork and ZINC databases. 2,621 compounds were screened against the modeled Pf 5-ALAS using AutoDock vina. The post-screening analysis was carried out using Discovery Studio while molecular dynamics simulation was performed on the best hits using NAMD-VMD and Galaxy Europe platform. Compound CSMS00081585868 was observed as the best hit with a binding affinity of -9.9 kcal/mol and predicted Ki of 52.10 nM, engaging in seven hydrogen bonds with the target’s active site amino acid residues. The in silico ADMET prediction showed that all ten best hits possessed relatively good pharmacokinetic properties. The qualitative structural assessment of the best hit, CSMS00081585868, revealed that the presence of two pyridine scaffolds bearing hydroxy and fluorine groups linked by a pyrrolidine scaffold contributed significantly to its ability to have a strong binding affinity with the receptor. The best hit also showed stability in the active site of Pf 5-ALAS as confirmed from the RMSD obtained during the MD simulation.
Case report: Corticosteroid-resistant acute fibrinous and organizing pneumonia with myelodysplastic syndrome
Authors: Jiang Dingyuan , Chen Xueying , Li Jun , Zhao Ling , Dai Huaping
Published: January 2023

Acute fibrinous and organizing pneumonia (AFOP) is a lung disease with an unusual pathological pattern. The definitive diagnosis of AFOP relies on pathological evidence of intra-alveolar fibrin exudate, lymphoplasmacytic infiltrate, and the absence of a hyaline membrane. Furthermore, its etiology is difficult to confirm, and corticosteroids are usually effective. Herein, we report the case of a young male who presented with high fever, hemocytopenia, and consolidation in both lungs. The initial misdiagnosis was community-acquired pneumonia. Subsequently, a lung biopsy revealed abundant fibrin and fibroblast exudates in the alveolar spaces, indicating AFOP. In addition, bone marrow biopsy and karyotype analysis demonstrated that the patient simultaneously had myelodysplastic syndrome (MDS) and hemophagocytic lymphohistiocytosis. In this case, the AFOP was considered secondary to MDS; however, the disease did not respond to glucocorticoid treatment or chemotherapy. Hence, AFOP should be considered in patients with underlying hematological diseases, and early identification and diagnosis are important. Furthermore, the management of patients with severe AFOP requires further investigation.