bluuebunny/crossref_metadata_2025_split huggingface dataset:
LEA motifs promote desiccation tolerance in vivo
Authors: Hibshman Jonathan D. , Goldstein Bob 
Published: December 2021

AbstractBackgroundCells and organisms typically cannot survive in the absence of water. However, some animals including nematodes, tardigrades, rotifers, and some arthropods are able to survive near-complete desiccation. One class of proteins known to play a role in desiccation tolerance is the late embryogenesis abundant (LEA) proteins. These largely disordered proteins protect plants and animals from desiccation. A multitude of studies have characterized stress-protective capabilities of LEA proteins in vitro and in heterologous systems. However, the extent to which LEA proteins exhibit such functions in vivo, in their native contexts in animals, is unclear. Furthermore, little is known about the distribution of LEA proteins in multicellular organisms or tissue-specific requirements in conferring stress protection. Here, we used the nematodeC. elegansas a model to study the endogenous function of an LEA protein in an animal.ResultsWe created a null mutant ofC. elegansLEA-1, as well as endogenous fluorescent reporters of the protein. LEA-1 mutant animals formed defective dauer larvae at high temperature. We confirmed thatC. eleganslacking LEA-1 are sensitive to desiccation. LEA-1 mutants were also sensitive to heat and osmotic stress and were prone to protein aggregation. During desiccation, LEA-1 expression increased and became more widespread throughout the body. LEA-1 was required at high levels in body wall muscle for animals to survive desiccation and osmotic stress, but expression in body wall muscle alone was not sufficient for stress resistance, indicating a likely requirement in multiple tissues. We identified minimal motifs withinC. elegansLEA-1 that were sufficient to increase desiccation survival ofE. coli. To test whether such motifs are central to LEA-1’s in vivo functions, we then replaced the sequence oflea-1with these minimal motifs and found thatC. elegansdauer larvae formed normally and survived osmotic stress and mild desiccation at the same levels as worms with the full-length protein.ConclusionsOur results provide insights into the endogenous functions and expression dynamics of an LEA protein in a multicellular animal. The results show that LEA-1 buffers animals from a broad range of stresses. Our identification of LEA motifs that can function in both bacteria and in a multicellular organism in vivo suggests the possibility of engineering LEA-1-derived peptides for optimized desiccation protection.
Influence of prefoldin subunit 4 on the tolerance of Kluyveromyces marxianus to lignocellulosic biomass-derived inhibitors
Authors: Zhang Nini , Shang Yingying , Wang Feier , Wang Dongmei , Hong Jiong 
Published: December 2021

AbstractBackgroundKluyveromyces marxianusis a potentially excellent host for microbial cell factories using lignocellulosic biomass, due to its thermotolerance, high growth rate, and wide substrate spectrum. However, its tolerance to inhibitors derived from lignocellulosic biomass pretreatment needs to be improved. The prefoldin complex assists the folding of cytoskeleton which relates to the stress tolerance, moreover, several subunits of prefoldin have been verified to be involved in gene expression regulation. With the presence of inhibitors, the expression of a gene coding the subunit 4 of prefoldin (KmPFD4), a possible transcription factor, was significantly changed. Therefore,KmPFD4was selected to evaluate its functions in inhibitors tolerance.ResultsIn this study, the disruption of the prefoldin subunit 4 gene (KmPFD4) led to increased concentration of intracellular reactive oxygen species (ROS) and disturbed the assembly of actin and tubulin in the presence of inhibitors, resulting in reduced inhibitor tolerance. Nuclear localization of KmPFD4 indicated that it could regulate gene expression. Transcriptomic analysis showed that upregulated gene expression related to ROS elimination, ATP production, and NAD+synthesis, which is a response to the presence of inhibitors, disappeared inKmPFD4-disrupted cells. Thus,KmPFD4impacts inhibitor tolerance by maintaining integration of the cytoskeleton and directly or indirectly affecting the expression of genes in response to inhibitors. Finally, overexpression ofKmPFD4enhanced ethanol fermentation with a 46.27% improvement in productivity in presence of the inhibitors.ConclusionThis study demonstrated thatKmPFD4plays a positive role in the inhibitor tolerance and can be applied for the development of inhibitor-tolerant platform strains.
C1QTNF6 promotes oral squamous cell carcinoma by enhancing proliferation and inhibiting apoptosis
Authors: Song Xiaobin , Li Longjie , Shi Liang , Liu Xinyu , Qu Xun , Wei Fengcai , Wang Ketao 
Published: December 2021

Abstract
Background
C1QTNF6 (CTRP6), a member of the CTRP family, has recently been implied to play a role in the tumorigenesis of for a variety of cancer types. However, the role of C1QTNF6 in oral squamous cell carcinoma (OSCC) and its potential molecular remains unclear.

Methods
C1QTNF6 expression was detected by qRT-PCR and western blot analysis. Lentiviral vectors were constructed to knockdown C1QTNF6 in CaL27 and SCC-9 human OSCC cell lines. Cell viability, cell cycle and cell apoptosis analyses were performed by MTT assay, PI/Annexin V staining, and flow cytometry. The effect of C1QTNF6 knockdown on in vivo tumorigenicity of OSCC cells in vivo was evaluated using nude mouse xenograft tumor model. Downstream signaling mechanisms were identified by microarray and Ingenuity Pathway Analysis.

Results
Immunohistochemistry of OSCC tissue and data from TCGA demonstrate that C1QTNF6 was overexpressed in OSCC tissues, and that cellular proliferation was significantly decreased after C1QTNF6 was knockdown in CaL27 and SCC-9 cell lines. Knockdown of C1QTNF6 also resulted in cell cycle arrest at the G2/M phase and enhanced cell apoptosis in in CaL27 and SCC-9 cell lines. Furthermore, knockdown of C1QTNF6 in Cal-27 cells inhibited tumor growth of OSCC in vivo. Microarray analysis revealed that C1QTNF6 silencing resulted in significant alterations of gene expression, with the Acute Phase Response signaling pathway significantly activated following C1QTNF6 silencing.

Conclusions
These results suggest that C1QTNF6 plays an important role in promoting OSCC tumorigenesis, which indicates that C1QTNF6 may comprise a promising therapeutic target for OSCC treatment.
ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation
Authors: Qiu Bai-Quan , Lin Xia-Hui , Lai Song-Qing , Lu Feng , Lin Kun , Long Xiang , Zhu Shu-Qiang , Zou Hua-Xi , Xu Jian-Jun , Liu Ji-Chun , Wu Yong-Bing 
Published: December 2021

Abstract
Background
Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study.

Methods
Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells.

Results
We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes.

Conclusion
Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.
Comprehensive analysis of pyroptosis regulators and tumor immune microenvironment in clear cell renal cell carcinoma
Authors: Zhang Yan , Chen Xianwu , Fu Qinghe , Wang Feifan , Zhou Xuejian , Xiang Jiayong , He Ning , Hu Zhenghui , Jin Xiaodong 
Published: December 2021

Abstract
Background
Increasing evidence has indicated that pyroptosis could regulate the tumor immune microenvironment (TIME) to affect the tumor development. As a highly immunogenic tumor, clear cell renal cell carcinoma (ccRCC) can benefit from immunotherapy, but related research on pyroptosis in the TIME of ccRCC is still deficient.

Methods
Available data derived from TCGA and GEO databases were analyzed to identify the different expression profiles of pyroptosis in ccRCC and normal tissues, and the correlation of pyroptosis regulators with TIME was evaluated in ccRCC.

Results
According to consensus clustering analysis, two differential expression levels of subtypes were identified to affect patient prognosis, and were related to histological tumor stage and grade. Immune cells were calculated by the CIBERSORT algorithm. Higher infiltrated levels of B cells naive, T cells CD4 memory resting, NK cells resting, monocytes, macrophages were observed in Cluster 1, while higher infiltrated levels of CD8+ T cells, T follicular helper cells, and Tregs were observed in Cluster 2. Gene set enrichment analysis indicated that Cluster 2 was enriched in multiple immune-related pathways, including the JAK-STAT signaling pathway. Moreover, overexpression of eight immune checkpoints was related to ccRCC development, especially in Cluster 2. As four potentially key pyroptosis regulators, AIM2, CASP5, NOD2, and GZMB were confirmed to be upregulated in ccRCC by RT-qPCR analysis and further verified by the HPA database. Further pan-cancer analysis suggested that these four pyroptosis regulators were differentially expressed and related to the TIME in multiple cancers.

Conclusion
The present study provided a comprehensive view of pyroptosis regulators in the TIME of ccRCC, which may provide potential value for immunotherapy.
Identification of crucial genes of pyrimidine metabolism as biomarkers for gastric cancer prognosis
Authors: Wu Zhengxin , Tan Jinshui , Zhuang Yifan , Zhong Mengya , Xiong Yubo , Ma Jingsong , Yang Yan , Gao Zhi , Zhao Jiabao , Ye Zhijian , Zhou Huiwen , Zhu Yuekun , Lu Haijie , Hong Xuehui 
Published: December 2021

Abstract
Background
Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear.

Methods
Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan–Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR.

Results
Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan–Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model.

Conclusion
In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.
CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606
Authors: Chen Yankun , Xu Simiao , Liu Xinyuan , Jiang Xueyi , Jiang Jianxin 
Published: December 2021

Abstract
Background
Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear.

Methods
Real-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies.

Results
The expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer.

Conclusions
These findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.
Investigating molecular mechanisms of insecticide resistance in the Eastern Democratic Republic of the Congo
Authors: Bandibabone Janvier , McLoughlin Charles , N’Do Sévérin , Bantuzeko Chimanuka , Byabushi Vital , Jeanberckmans Muhigwa , Guardiola Maite , Zawadi Bertin , Diabaté Abdoulaye , Prudhomme Jorian , Walker Thomas , Messenger Louisa A. 
Published: December 2021

Abstract
Background
Malaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited.

Methods
Adult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring.

Results
L1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively.

Conclusions
This study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.
Regulating the production and biological function of small extracellular vesicles: current strategies, applications and prospects
Authors: Luo Lei , Wu Zhi , Wang Yang , Li Haiyan 
Published: December 2021

AbstractNumerous studies have confirmed the great application potentials of small extracellular vesicles (sEVs) in biological medical field, especially in tissue repair and regeneration. However, the production capability of sEVs by noncancerous cells is very limited, while their dosage requirements in disease treatments are usually very high. Meanwhile, as cell aging, the sEV production capability of cells decreases and the biological function of sEVs changes accordingly. In addition, for special applications, sEVs carrying desired bioactive substances should be designed to perform their expected biological function. Therefore, improving the production of sEVs and precisely regulating their biological function are of great significance for promoting the clinical applications of sEVs. In this review, some of the current classic strategies in affecting the cellular behaviors of donor cells and subsequently regulating the production and biological function of their sEVs are summarized, including gene engineering methods, stress-inducing conditions, chemical regulators, physical methods, and biomaterial stimulations. Through applying these strategies, increased yield of sEVs with required biological function can be obtained for disease treatment and tissue repair, such as bone regeneration, wound healing, nerve function recovery and cancer treatment, which could not only reduce the harvest cost of sEV but promote the practical applications of sEVs in clinic.
Graphical Abstract
Irinotecan/scFv co-loaded liposomes coaction on tumor cells and CAFs for enhanced colorectal cancer therapy
Authors: Li Zhaohuan , Liu Chunxi , Li Chenglei , Wang Fangqing , Liu Jianhao , Zheng Zengjuan , Wu Jingliang , Zhang Bo 
Published: December 2021

Abstract
Background
Cancer-associated fibroblasts (CAFs), as an important component of stroma, not only supply the “soils” to promote tumor invasion and metastasis, but also form a physical barrier to hinder the penetration of therapeutic agents. Based on this, the combinational strategy that action on both tumor cells and CAFs simultaneously would be a promising approach for improving the antitumor effect.

Results
In this study, the novel multifunctional liposomes (IRI-RGD/R9-sLip) were designed, which integrated the advantages including IRI and scFv co-loading, different targets, RGD mediated active targeting, R9 promoting cell efficient permeation and lysosomal escape. As expected, IRI-RGD/R9-sLip showed enhanced cytotoxicity in different cell models, effectively increased the accumulation in tumor sites, as well as exhibited deep permeation ability both in vitro and in vivo. Notably, IRI-RGD/R9-sLip not only exhibited superior in vivo anti-tumor effect in both CAFs-free and CAFs-abundant bearing mice models, but also presented excellent anti-metastasis efficiency in lung metastasis model.

Conclusion
In a word, the novel combinational strategy by coaction on both “seeds” and “soils” of the tumor provides a new approach for cancer therapy, and the prepared liposomes could efficiently improve the antitumor effect with promising clinical application prospects.

Graphical Abstract
Morphologic change in deep venous thrombosis in the lower extremity after therapeutic anticoagulation
Authors: Panpikoon Tanapong , Phattharaprueksa Wisanu , Treesit Tharintorn , Bua-ngam Chinnarat , Pichitpichatkul Kaewpitcha , Sriprachyakul Apichaya 
Published: December 2021

Abstract
Background
To evaluate the anticoagulant treatment response in venous thrombi with different morphologies (size, shape, and echogenicity) by measuring the change in thrombus thickness.

Materials and methods
This was a retrospective cohort study of 97 lower extremity DVT patients diagnosed by venous ultrasound between March 2014 and February 2018. The demographics, clinical risk factors, anticoagulant treatment, and ultrasound findings at the first diagnosis and 2–6 months after treatment were evaluated.

Results
The anticoagulant treatment with LMWH followed by VKAs showed a significant decrease in the mean maximum difference in lower extremity DVT thrombus thickness compared with VKAs alone (P-value < 0.001). After adjustment by treatment, the thrombi found in dilated veins showed a significant decrease in the thickness of such thrombi compared with those found in small veins: 4 mm vs. 0 mm (Coef. = 3, 95% CI: 1.9, 4.1 and P-value < 0.001). Anechoic and hypoechoic thrombi showed a significant decrease in the thickness compared with hyperechoic thrombi: 5 mm vs. 0 mm (Coef. = 4, 95% CI: 3.25, 4.74 and P-value < 0.001) and 3 mm vs. 0 mm (Coef. = 2, 95% CI: 1.34, 42.66 and P-value < 0.001), respectively. Concentric thrombi showed a significant decrease in thickness compared with eccentric thrombi: 4 mm vs. 0 mm (Coef. = 2, 95% CI: 1.45, 2.55 and P-value < 0.001).

Conclusion
The anticoagulant treatment with LMWH followed by VKAs shows a significant decrease in lower extremity DVT thrombus thickness compared with VKAs alone. After adjustment by treatment, the morphologic finding of acute thrombi shows a significantly decreased thickness compared with the morphologic finding of chronic thrombi.