bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora
Authors: Eldeghidy Abeer , Abdel-Fattah Gamal , El-Sayed Ashraf S. A. , Abdel-Fattah Ghada G. 
Published: August 2023

AbstractFungal producing potency of camptothecin (CPT) raise the hope for their usage to be a platform for industrial production of CPT, nevertheless, attenuation of their productivity of CPT with the subculturing and preservation is the challenge. So, screening for novel endophytic fungal isolates with a reliable CPT-biosynthetic stability was the objective. Among the isolated endophytic fungi from the tested medicinal plants, Aspergillus terreus OQ642314.1, endophyte of Cinnamomum camphora, exhibits the highest yield of CPT (89.4 μg/l). From the NMR, FT-IR and LC–MS/MS analyses, the extracted CPT from A. terreus gave the same structure and molecular mass fragmentation pattern of authentic CPT (349 m/z). The putative CPT had a significant activity against MCF7 (0.27 µM) and HEPG-2 (0.8 µM), with a strong affinity to inhibits the human Topoisomerase 1 activity (IC50 0.362 μg/ml) as revealed from the Gel-based DNA relaxation assay. The purified CPT displayed a strong antimicrobial activity for various bacterial (E. coli and B. cereus) and fungal (A. flavus and A. parasiticus) isolates, ensuring the unique tertiary, and stereo-structure of A. terreus for penetrating the microbial cell walls and targeting the topoisomerase I. The higher dual activity of the purified CPT as antimicrobial and antitumor, emphasize their therapeutic efficiency, especially with growth of the opportunistic microorganisms due to the suppression of human immune system with the CPT uses in vivo. The putative CPT had an obvious activity against the tumor cell (MCF7) metastasis, and migration as revealed from the wound healing assay. The overall yield of A. terreus CPT was maximized with the Blackett-Burman design by twofolds increment (164.8 μg/l). The CPT yield by A. terreus was successively diminished with the multiple fungal subculturing, otherwise, the CPT productivity of A. terreus was restored, and increased over the zero culture upon coculturing with C. camphora microbiome (1.5% w/v), ensuring the restoring of CPT biosynthetic potency of A. terreus by the plant microbiome-derived chemical signals “microbial communication”. This is the first report exploring the feasibility of A. terreus “endophyte of C. camphora” to be a preliminary platform for commercial production of CPT with a reliable sustainability upon uses of indigenous C. camphora microbiome.
Semaphorin 3 C enhances putative cancer stemness and accelerates peritoneal dissemination in pancreatic cancer
Authors: Tomizawa Satoshi , Takano Shigetsugu , Eto Ryotaro , Takayashiki Tsukasa , Kuboki Satoshi , Ohtsuka Masayuki 
Published: August 2023

Abstract
Purpose
Semaphorins, axon guidance cues in neuronal network formation, have been implicated in cancer progression. We previously identified semaphorin 3 C (SEMA3C) as a secreted protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). We, therefore, hypothesized that SEMA3C supports PDAC progression. In this study, we aimed to investigate the clinical features of SEMA3C, especially its association with chemo-resistance and peritoneal dissemination.

Methods
In resected PDAC tissues, we assessed the relationship between SEMA3C expression and clinicopathological features by immunohistochemistry. In vitro studies, we have shown invasion assay, pancreatosphere formation assay, colony formation assay, cytotoxicity assay, and activation of SEMA3C downstream targets (c-Met, Akt, mTOR). In vivo, we performed a preclinical trial to confirm the efficacy of SEMA3C shRNA knockdown and Gemcitabine and nab-Paclitaxel (GnP) in an orthotopic transplantation mouse model and in peritoneal dissemination mouse model.

Results
In resected PDAC tissues, SEMA3C expression correlated with invasion and peritoneal dissemination after surgery. SEMA3C promoted cell invasion, self-renewal, and colony formation in vitro. We further demonstrated that SEMA3C knockdown increased Gem-induced cytotoxicity by suppressing the activation of the Akt/mTOR pathway via the c-Met receptor. Combination therapy with SEMA3C knockdown and GnP reduced tumor growth and peritoneal dissemination.

Conclusions
SEMA3C enhances peritoneal dissemination by regulating putative cancer stemness and Gem resistance and activates phosphorylation of the Akt/mTOR pathway via c-Met. Our findings provide a new avenue for therapeutic strategies in regulating peritoneal dissemination during PDAC progression.
Selenium nanoparticles based on Amphipterygium glaucum extract with antibacterial, antioxidant, and plant biostimulant properties
Authors: Garza-García Jorge J. O. , Hernández-Díaz José A. , León-Morales Janet M. , Velázquez-Juárez Gilberto , Zamudio-Ojeda Adalberto , Arratia-Quijada Jenny , Reyes-Maldonado Oscar K. , López-Velázquez Julio C. , García-Morales Soledad 
Published: August 2023

Abstract
Background
In recent years, crop production has expanded due to the variety of commercially available species. This increase in production has led to global competition and the search for biostimulant products that improve crop quality and yield. At the same time, agricultural products that protect against diseases caused by phytopathogenic microorganisms are needed. Thus, the green synthesis of selenium nanoparticles (SeNPs) is a proposal for achieving these needs. In this research, SeNPs were synthesized from methanolic extract of Amphipterygium glaucum leaves, and chemically and biologically characterized.

Results
The characterization of SeNPs was conducted by ultraviolet–visible spectrophotometry (UV–Vis), scanning electron microscopy (SEM), electron microscopy transmission (TEM), Dynamic Light Scattering (DLS), energy dispersion X-ray spectroscopy (EDX), and infrared spectrophotometry (FTIR) techniques. SeNPs with an average size of 40–60 nm and spherical and needle-shaped morphologies were obtained. The antibacterial activity of SeNPs against Serratia marcescens, Enterobacter cloacae, and Alcaligenes faecalis was evaluated. The results indicate that the methanolic extracts of A. glaucum and SeNPs presented a high antioxidant activity. The biostimulant effect of SeNPs (10, 20, 50, and 100 µM) was evaluated in vinca (Catharanthus roseus), and calendula (Calendula officinalis) plants under greenhouse conditions, and they improved growth parameters such as the height, the fresh and dry weight of roots, stems, and leaves; and the number of flowers of vinca and calendula.

Conclusions
The antibacterial, antioxidant, and biostimulant properties of SeNPs synthesized from A. glaucum extract demonstrated in this study support their use as a promising tool in crop production.

Graphical Abstract
Decreased MFN2 activates the cGAS-STING pathway in diabetic myocardial ischaemia–reperfusion by triggering the release of mitochondrial DNA
Authors: Xiong Yonghong , Leng Yan , Tian Hao , Deng Xinqi , Li Wenyuan , Li Wei , Xia Zhongyuan 
Published: August 2023

AbstractBackgroundThe cause of aggravation of diabetic myocardial damage is yet to be elucidated; damage to mitochondrial function has been a longstanding focus of research. During diabetic myocardial ischaemia–reperfusion (MI/R), it remains unclear whether reduced mitochondrial fusion exacerbates myocardial injury by generating free damaged mitochondrial DNA (mitoDNA) and activating the cGAS-STING pathway.MethodsIn this study, a mouse model of diabetes was established (by feeding mice a high-fat diet (HFD) plus a low dose of streptozotocin (STZ)), a MI/R model was established by cardiac ischaemia for 2 h and reperfusion for 30 min, and a cellular model of glycolipid toxicity induced by high glucose (HG) and palmitic acid (PA) was established in H9C2 cells.ResultsWe observed that altered mitochondrial dynamics during diabetic MI/R led to increased mitoDNA in the cytosol, activation of the cGAS-STING pathway, and phosphorylation of the downstream targets TBK1 and IRF3. In the cellular model we found that cytosolic mitoDNA was the result of reduced mitochondrial fusion induced by HG and PA, which also resulted in cGAS-STING signalling and activation of downstream targets. Moreover, inhibition of STING by H-151 significantly ameliorated myocardial injury induced by MFN2 knockdown in both the cell and mouse models. The use of a fat-soluble antioxidant CoQ10 improved cardiac function in the mouse models.ConclusionsOur study elucidated the critical role of cGAS-STING activation, triggered by increased cytosolic mitoDNA due to decreased mitochondrial fusion, in the pathogenesis of diabetic MI/R injury. This provides preclinical insights for the treatment of diabetic MI/R injury.Graphical Abstract
The pattern and spread of invasion can predict late cervical lymph node metastasis in early tongue squamous cell carcinoma
Authors: Kato Koroku , Miyazawa Hiroki , Kobayashi Hisano , Kishikawa Yoshiaki , Funaki Hayato , Noguchi Natsuyo , Ooi Kazuhiro , Kawashiri Shuichi 
Published: August 2023

AbstractTo determine the predictive indexes of late cervical lymph node metastasis in early tongue squamous cell carcinoma (TSCC). We retrospectively analyzed the cases of 25 patients with stage I/II TSCC who had undergone surgical treatment without elective neck dissection. We evaluated the relationships between clinicopathologic factors and the occurrence of late cervical lymph node metastasis. Of the 25 cases, metastasis to the cervical lymph nodes was observed in nine cases (36.0%). The clinicopathological factors associated with late cervical lymph node metastasis were the mode of invasion (MOI, p = 0.032), depth of invasion (DOI, p = 0.004), and perineural invasion (PNI, p = 0.040). A multivariate analysis revealed that only the DOI was an independent predictor of late cervical lymph node metastasis. The combination of the DOI and MOI or the PNI and MOI was significantly correlated with late cervical lymph node metastasis (p = 0.004 and p = 0.012, respectively). Our findings suggest that combinations of the MOI, DOI, and PNI could be used as an index for predicting late cervical lymph node metastasis in early TSCC.
Development of cassava common mosaic virus-based vector for protein expression and gene editing in cassava
Authors: Tuo Decai , Yao Yuan , Yan Pu , Chen Xin , Qu Feihong , Xue Weiqian , Liu Jinping , Kong Hua , Guo Jianchun , Cui Hongguang , Dai Zhaoji , Shen Wentao 
Published: August 2023

Abstract
Background
Plant virus vectors designed for virus-mediated protein overexpression (VOX), virus-induced gene silencing (VIGS), and genome editing (VIGE) provide rapid and cost-effective tools for functional genomics studies, biotechnology applications and genome modification in plants. We previously reported that a cassava common mosaic virus (CsCMV, genus Potexvirus)-based VIGS vector was used for rapid gene function analysis in cassava. However, there are no VOX and VIGE vectors available in cassava.

Results
In this study, we developed an efficient VOX vector (CsCMV2-NC) for cassava by modifying the CsCMV-based VIGS vector. Specifically, the length of the duplicated putative subgenomic promoter (SGP1) of the CsCMV CP gene was increased to improve heterologous protein expression in cassava plants. The modified CsCMV2-NC-based VOX vector was engineered to express genes encoding green fluorescent protein (GFP), bacterial phytoene synthase (crtB), and Xanthomonas axonopodis pv. manihotis (Xam) type III effector XopAO1 for viral infection tracking, carotenoid biofortification and Xam virulence effector identification in cassava. In addition, we used CsCMV2-NC to deliver single guide RNAs (gMePDS1/2) targeting two loci of the cassava phytoene desaturase gene (MePDS) in Cas9-overexpressing transgenic cassava lines. The CsCMV-gMePDS1/2 efficiently induced deletion mutations of the targeted MePDS with the albino phenotypes in systemically infected cassava leaves.

Conclusions
Our results provide a useful tool for rapid and efficient heterologous protein expression and guide RNA delivery in cassava. This expands the potential applications of CsCMV-based vector in gene function studies, biotechnology research, and precision breeding for cassava.
Novel scheme for defining the clinical implications of TP53 mutations in myeloid neoplasia
Authors: Bahaj Waled , Kewan Tariq , Gurnari Carmelo , Durmaz Arda , Ponvilawan Ben , Pandit Ishani , Kubota Yasuo , Ogbue Olisaemeka D. , Zawit Misam , Madanat Yazan , Bat Taha , Balasubramanian Suresh K. , Awada Hussein , Ahmed Ramsha , Mori Minako , Meggendorfer Manja , Haferlach Torsten , Visconte Valeria , Maciejewski Jaroslaw P. 
Published: August 2023

Abstract
Background
TP53 mutations (TP53MT) occur in diverse genomic configurations. Particularly, biallelic inactivation is associated with poor overall survival in cancer. Lesions affecting only one allele might not be directly leukemogenic, questioning the presence of cryptic biallelic subclones in cases with dismal prognosis.

Methods
We have collected clinical and molecular data of 7400 patients with myeloid neoplasms and applied a novel model by identifying an optimal VAF cutoff using a statistically robust strategy of sampling-based regression on survival data to accurately classify the TP53 allelic configuration and assess prognosis more precisely.

Results
Overall, TP53MT were found in 1010 patients. Following the traditional criteria, 36% of the cases were classified as single hits, while 64% exhibited double hits genomic configuration. Using a newly developed molecular algorithm, we found that 579 (57%) patients had unequivocally biallelic, 239 (24%) likely contained biallelic, and 192 (19%) had most likely monoallelic TP53MT. Interestingly, our method was able to upstage 192 out of 352 (54.5%) traditionally single hit lesions into a probable biallelic category. Such classification was further substantiated by a survival-based model built after re-categorization. Among cases traditionally considered monoallelic, the overall survival of those with probable monoallelic mutations was similar to the one of wild-type patients and was better than that of patients with a biallelic configuration. As a result, patients with certain biallelic hits, regardless of the disease subtype (AML or MDS), had a similar prognosis. Similar results were observed when the model was applied to an external cohort. In addition, single-cell DNA studies unveiled the biallelic nature of previously considered monoallelic cases.

Conclusion
Our novel approach more accurately resolves TP53 genomic configuration and uncovers genetic mosaicism for the use in the clinical setting to improve prognostic evaluation.
BEDwARS: a robust Bayesian approach to bulk gene expression deconvolution with noisy reference signatures
Authors: Ghaffari Saba , Bouchonville Kelly J. , Saleh Ehsan , Schmidt Remington E. , Offer Steven M. , Sinha Saurabh 
Published: August 2023

AbstractDifferential gene expression in bulk transcriptomics data can reflect change of transcript abundance within a cell type and/or change in the proportions of cell types. Expression deconvolution methods can help differentiate these scenarios. BEDwARS is a Bayesian deconvolution method designed to address differences between reference signatures of cell types and corresponding true signatures underlying bulk transcriptomic profiles. BEDwARS is more robust to noisy reference signatures and outperforms leading in-class methods for estimating cell type proportions and signatures. Application of BEDwARS to dihydropyridine dehydrogenase deficiency identified the possible involvement of ciliopathy and impaired translational control in the etiology of the disorder.
A syntelog-based pan-genome provides insights into rice domestication and de-domestication
Authors: Wu Dongya , Xie Lingjuan , Sun Yanqing , Huang Yujie , Jia Lei , Dong Chenfeng , Shen Enhui , Ye Chu-Yu , Qian Qian , Fan Longjiang 
Published: August 2023

Abstract
Background
Asian rice is one of the world’s most widely cultivated crops. Large-scale resequencing analyses have been undertaken to explore the domestication and de-domestication genomic history of Asian rice, but the evolution of rice is still under debate.

Results
Here, we construct a syntelog-based rice pan-genome by integrating and merging 74 high-accuracy genomes based on long-read sequencing, encompassing all ecotypes and taxa of Oryza sativa and Oryza rufipogon. Analyses of syntelog groups illustrate subspecies divergence in gene presence-and-absence and haplotype composition and identify massive genomic regions putatively introgressed from ancient Geng/japonica to ancient Xian/indica or its wild ancestor, including almost all well-known domestication genes and a 4.5-Mbp centromere-spanning block, supporting a single domestication event in main rice subspecies. Genomic comparisons between weedy and cultivated rice highlight the contribution from wild introgression to the emergence of de-domestication syndromes in weedy rice.

Conclusions
This work highlights the significance of inter-taxa introgression in shaping diversification and divergence in rice evolution and provides an exploratory attempt by utilizing the advantages of pan-genomes in evolutionary studies.
Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers
Authors: Idris Musa , Coussement Louis , Alves Maria M. , De Meyer Tim , Melotte Veerle 
Published: August 2023

Abstract
Background
DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA).

Results
All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature.

Conclusion
Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells.
Joint DNN partitioning and task offloading in mobile edge computing via deep reinforcement learning
Authors: Zhang Jianbing , Ma Shufang , Yan Zexiao , Huang Jiwei 
Published: August 2023

AbstractAs Artificial Intelligence (AI) becomes increasingly prevalent, Deep Neural Networks (DNNs) have become a crucial tool for developing and advancing AI applications. Considering limited computing and energy resources on mobile devices (MDs), it is a challenge to perform compute-intensive DNN tasks on MDs. To attack this challenge, mobile edge computing (MEC) provides a viable solution through DNN partitioning and task offloading. However, as the communication conditions between different devices change over time, DNN partitioning on different devices must also change synchronously. This is a dynamic process, which aggravates the complexity of DNN partitioning. In this paper, we delve into the issue of jointly optimizing energy and delay for DNN partitioning and task offloading in a dynamic MEC scenario where each MD and the server adopt the pre-trained DNNs for task inference. Taking advantage of the characteristics of DNN, we first propose a strategy for layered partitioning of DNN tasks to divide the task of each MD into subtasks that can be either processed on the MD or offloaded to the server for computation. Then, we formulate the trade-off between energy and delay as a joint optimization problem, which is further represented as a Markov decision process (MDP). To solve this, we design a DNN partitioning and task offloading (DPTO) algorithm utilizing deep reinforcement learning (DRL), which enables MDs to make optimal offloading decisions. Finally, experimental results demonstrate that our algorithm outperforms existing non-DRL and DRL algorithms with respect to processing delay and energy consumption, and can be applied to different DNN types.
Association of weight-adjusted-waist index with non-alcoholic fatty liver disease and liver fibrosis: a cross-sectional study based on NHANES
Authors: Hu Qinggang , Han Kexing , Shen Jiapei , Sun Weijie , Gao Long , Gao Yufeng 
Published: August 2023

Abstract
Aim
The purpose of this study was to explore the association of weight-adjusted-waist index (WWI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis.

Methods
A cross-sectional study including 6587 participants was conducted in the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression was used to validate the association of WWI with NAFLD and liver fibrosis, and smoothed curve fitting and threshold effect models were used to validate non-linear relationships. Subgroup analyses were used to verify the stability of the relationship between the independent and dependent variables in different populations.

Results
There was a positive association of WWI with NAFLD and liver fibrosis. In the model adjusted for all covariates, the effect values of WWI with NAFLD and liver fibrosis were (OR = 3.44, 95% CI: 3.09–3.82) and (OR = 2.40, 95% CI: 2.05–2.79), respectively. This positive correlation became more significant as WWI increased when WWI was presented in quartiles (P for trend < 0.01). Smoothed curve fitting and threshold effects analysis suggested a non-linear correlation between WWI and NAFLD (LLR < 0.01), with the positive correlation between WWI and NAFLD becoming more significant when WWI was less than 11.44 [5.93 (95% CI: 5.04–6.98)]. However, there was a linear correlation between WWI and liver fibrosis (LLR = 0.291). When subgroup analyses were performed by indicators such as age, race and gender, we found that the positive association between WWI and the dependent variables (NAFLD and liver fibrosis) was more pronounced in white male participants aged < 40 years.

Conclusions
Among adults in the United States, WWI was positively associated with the prevalence of NAFLD and liver fibrosis. Participants with a WWI less than 11.44 should be cautious about the possibility of an increased risk of NAFLD development due to a higher WWI. Meanwhile, white males younger than 40 years of age should be more cautious about the higher risk of NAFLD and liver fibrosis that might be associated with an increased WWI.