bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines
Authors: Zhang Bin , Sim Wei Kian , Shen Tang-Long , Lim Sai Kiang 
Published: January 2024

AbstractExtracellular vesicles (EVs) are tiny, lipid membrane-bound structures that are released by most cells. They play a vital role in facilitating intercellular communication by delivering bioactive cargoes to recipient cells and triggering cellular as well as biological responses. EVs have enormous potential for therapeutic applications as native or engineered exosomes. Native EVs are naturally released by cells without undergoing any modifications to either the exosomes or the cells that secrete them. In contrast, engineered EVs have been deliberately modified post-secretion or through genetic engineering of the secreting cells to alter their composition. Here we propose that engineered EVs displaying pathogen proteins could serve as promising alternatives to lipid nanoparticle (LNP)-mRNA vaccines. By leveraging their unique characteristics, these engineered EVs have the potential to overcome certain limitations associated with LNP-mRNA vaccines.
Bioproduction and optimization of newly characterized melanin pigment from Streptomyces djakartensis NSS-3 with its anticancer, antimicrobial, and radioprotective properties
Authors: El-Zawawy Nessma A. , Kenawy El-Refaie , Ahmed Sara , El-Sapagh Shimaa 
Published: January 2024

Abstract
Background
Melanin is a natural pigment that is considered a promising biomaterial for numerous biotechnological applications across several industries. Melanin has biomedical applications as antimicrobial, anticancer, and antioxidant properties. Additionally, in the pharmaceutical and cosmetic industries, it is used in drug delivery and as a radioprotective agent. Also, melanin has environmental uses in the fields of bioremediation and the food industry. The biosynthesis of melanin pigment is an area of interest for researchers due to its multifunctionality, high compatibility, and biodegradability. Therefore, our present work is the first attempt to characterize and optimize the productivity of melanin pigment from Streptomyces djakartensis NSS-3 concerning its radioprotection and biological properties.

Results
Forty isolates of soil actinobacteria were isolated from the Wadi Allaqui Biosphere Reserve, Egypt. Only one isolate, ACT3, produced a dark brown melanin pigment extracellularly. This isolate was identified according to phenotypic properties and molecular phylogenetic analysis as Streptomyces djakartensis NSS-3 with accession number OP912881. Plackett–Burman experimental design (PBD) and response surface methodology (RSM) using a Box-Behnken design (BBD) were performed for optimum medium and culturing conditions for maximum pigment production, resulting in a 4.19-fold improvement in melanin production (118.73 mg/10 mL). The extracted melanin pigment was purified and characterized as belonging to nitrogen-free pyomelanin based on ultraviolet–visible spectrophotometry (UV–VIS), Fourier transform infrared (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and NMR studies. Purified melanin demonstrated potent scavenging activity with IC50 values of 18.03 µg/mL and revealed high potency as sunscreens (in vitro SPF = 18.5). Moreover, it showed a nontoxic effect on a normal cell line (WI38), while it had a concentration-dependent anticancer effect on HCT116, HEPG, and MCF7 cell lines with IC50 = 108.9, 43.83, and 81.99 µg/mL, respectively. Also, purified melanin had a detrimental effect on the tested MDR bacterial strains, of which PA-09 and SA-04 were clearly more susceptible to melanin compared with other strains with MICs of 6.25 and 25 µg/mL, respectively.

Conclusion
Our results demonstrated that the newly characterized pyomelanin from Streptomyces djakartensis NSS-3 has valuable biological properties due to its potential photoprotective, antioxidant, anticancer, antimicrobial, and lack of cytotoxic activities, which open up new prospects for using this natural melanin pigment in various biotechnological applications and avoiding chemical-based drugs.
USP29 activation mediated by FUBP1 promotes AURKB stability and oncogenic functions in gastric cancer
Authors: Tu Rongfu , Kang Ye , Pan Yiwen , Da Yanyan , Ren Doudou , Zhang Ru , Cai Zeqiong , Liu Yijia , Xu Jiao , Ma Junpeng , Zhou Zhiyong , Yin Shupeng , Li Xiaozhuang , Zhang Peng , Zhang Qi , Wang Jingchao , Lu Xinlan , Zhang Chengsheng 
Published: January 2024

AbstractBackgroundGastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear.MethodsThe expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, andUsp29knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays.ResultsIn this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout ofUsp29in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues.ConclusionsThese findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.
Recent advances in the potential role of RNA N4-acetylcytidine in cancer progression
Authors: Zhang Shujun , Liu Yafeng , Ma Xiao , Gao Xiaohui , Ru Yi , Hu Xinjun , Gu Xinyu 
Published: January 2024

AbstractN4-acetylcytidine (ac4C) is a highly conserved chemical modification widely found in eukaryotic and prokaryotic RNA, such as tRNA, rRNA, and mRNA. This modification is significantly associated with various human diseases, especially cancer, and its formation depends on the catalytic activity of N-acetyltransferase 10 (NAT10), the only known protein that produces ac4C. This review discusses the detection techniques and regulatory mechanisms of ac4C and summarizes ac4C correlation with tumor occurrence, development, prognosis, and drug therapy. It also comments on a new biomarker for early tumor diagnosis and prognosis prediction and a new target for tumor therapy.
Shih-Tzu dogs show alterations in ocular surface homeostasis despite adequate aqueous tear production
Authors: Vitor Rebeca Costa , de Carvalho Teixeira Jamille Bispo , dos Santos Katharine Costa , Oliveira Gabriela Mota Sena de , Guedes Paula Elisa Brandão , da Paixão Sevá Anaiá , Gomes Junior Deusdete Conceição , Veloso Jéssica Fontes , Carlos Renata Santiago Alberto 
Published: January 2024

Abstract
Background
Shih-Tzu dogs are frequently affected by ocular surface disorders such as corneal ulceration and dry eye disease (DED). The aim of this study was to evaluate ocular surface homeostasis in Shih-Tzu dogs that have adequate aqueous production. Twenty-eight dogs were subjected to eyelid blink counting, Schirmer tear test (STT-1), ophthalmic evaluation, tear film break-up time (TBUT), fluorescein test and Masmali tear ferning (TF) grading scale.

Results
Of the 28 animals evaluated, the median value of incomplete eyelid blinks/min (median = 15.0 blinks/min; Interquartil interval - IQR = 8.7 blinks/min − 19.5 blinks/min) was higher than the complete blinks/min (median = 2.5 blinks/min; IQR = 1.6 blinks/min − 4.3 blinks/min), with statistically significant difference. The Schirmer tear test had a median value of 25.0 mm/min (IQR = 22.7 mm/min − 27.5 mm/min), considered within the normal range for the species. On ophthalmic examination, all dogs had trichiasis of the caruncle and medial lower eyelid entropion. Lagophthalmos was the third most common alteration observed (71.4%; 20/28). The median of TBUT was 4.0 s; (IQR = 3.0 – 6.0 s). All the animals were negative to the fluorescein test and the TFT indicated that the majority of the eyes (51.8%; 29/56) were classified in abnormal grades 3 and 4 according to the Masmali tear ferning (TF) grading scale.

Conclusions
Although the Shith-Tzu dogs had STT-1 values within the normal range for the species there was high prevalence of abnormal TFT grades and low TBUT in all dogs, showing that despite adequate aqueous production, these dogs have poor precorneal tear film quality. In addition, the dogs showed few complete eyelid blinks and ophthalmic alterations, promoting poor tear film diffusion. All these findings, isolated or together, can result in DED.
Application of bacteria and bacteriophage cocktails for biological control of houseflies
Authors: Zhang Kexin , Wang Shumin , Li Ying , Yin Yansong , Zhang Xinyu , Zhang Qian , Kong Xinxin , Liu Wenjuan , Yao Dawei , Zhang Ruiling , Zhang Zhong 
Published: January 2024

Abstract
Background
Houseflies, Musca domestica L., are an ubiquitous pest that can transmit numerous diseases and threaten human health. Increasing insecticide resistance shown by houseflies necessitates the develop new control alternatives. The housefly gut is densely colonized with microorganisms that interact with each other dynamically and benefit the host’s health. However, the impact of multiple symbiotic bacteria on the composition of housefly gut microbiota and the host’s activities remains unclear.

Methods
We isolated and cultured 12 bacterial species from the intestines of housefly larvae. We also isolated seven bacteriophages to precisely target the regulation of certain bacterial species. Using 16S rRNA high-throughput gene sequencing, we analyzed the bacterial diversity after orally administering bacteria/phage cocktails to houseflies.

Results
Our results showed that larval growth was promoted, the abundance of beneficial bacteria, such as Klebsiella and Enterobacter, was increased and the abundance of harmful bacteria, such as Providencia, Morganella and Pseudomonas, was decreased in housefly larvae fed with the beneficial bacteria cocktail. However, oral administration of both beneficial and harmful bacterial phage cocktails inhibited larval growth, probably due to the drastic alteration of gut flora. Untargeted metabolomics using liquid chromatography–mass spectrometry showed that disturbances in gut microbiota changed the larval metabolite profiles. Feeding experiments revealed that disrupting the intestinal flora suppressed the beneficial bacteria and increased the harmful bacteria, causing changes in the metabolites and inhibiting larval growth.

Conclusions
Based on our results, bacteria/phage cocktails are effective tools for regulating the intestinal flora of insects and have a high potential as a biological control agent for incorporation into an integrated pest management program.

Graphical abstract
CXCL9 may serve as a potential biomarker for primary Sjögren’s syndrome with extra-glandular manifestations
Authors: Hong Jingwei , Cheng Hui , Wang Ping , Wu Yanzhi , Lu Saisai , Zhou Yan , Wang Xiao bing , Zhu Xiaofang 
Published: January 2024

Abstract
Background
Primary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM.

Methods
By utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma.

Results
A total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI.

Conclusion
CXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.
Liver indicators affecting the relationship between BMI and hypertension in type 2 diabetes: a mediation analysis
Authors: Yao Xuelin , Hu Keyan , Wang Zhen , Lu Fangting , Zhang Jie , Miao Yahu , Feng Qing , Jiang Tian , Zhang Yi , Tang Songtao , Zhang Nan , Dai Fang , Hu Honglin , Zhang Qiu ,   the China National Diabetic Chronic Complications Study Group
Published: January 2024

Abstract
Background
Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes.

Objective
To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM).

Methods
We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia.

Results
For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P < 0.05).

Conclusion
The effect of BMI on hypertension is partly mediated by liver indicators (ALT, AST, GGT, and AST/ALT) in diabetic patients. Our results may provide opportunities to identify new targets for hypertension interventions.
Difference in composition and functional analysis of bacterial communities between Mytilus galloprovincialis gills and surrounding water in a brackish inshore bay, analyzed by 16S rDNA multi-amplicon sequencing
Authors: Zardinoni Giulia , Deb Saptarathi , Ravi Samathmika , Giagnoni Lucia , Fumelli Piergiorgio , Tondello Alessandra , Dacasto Mauro , Squartini Andrea , Spanu Carlo , Trocino Angela , Stevanato Piergiorgio 
Published: January 2024

Abstract
Background
Lagoons are important natural systems, with attractive favorable conditions for aquaculture production, such as shellfish cultivation. Despite their socio-economic relevance for human activity, information on the microbial diversity, community composition, and putative functions of gill-associated microbiota and seawater is still limited, particularly as regards the extent of specific taxa enrichment within the gills and the relative effects of the temporal and spatial variables. In this study, we used a 16S rDNA multi-amplicon sequencing approach using an Ion GeneStudio S5 System and a function prediction method (Functional Annotation of Prokaryotic Taxa (FAPROTAX), to inspect the springtime dynamics of microbial communities and their inferred metabolic features in an Adriatic lagoon (Po Delta, Italy).

Results
Mussels and surrounding seawater were sampled in two rearing areas three times between April and June 2021. Sequencing results showed significant (p ≤ 0.05) differences in bacterial community composition and diversity between gills and seawater. Gills were dominated by the Methylobacterium-Methylorubrum and Burkholderia-Caballeronia-Paraburkholderia genera, while in seawater samples Izamaplasma, Planktomarina, and Candidatus Aquiluna were detected as being dominant. The microbiota composition did not differ significantly between the two rearing areas. The sampling time, although limited to a 3-month timeframe, instead revealed a structural variation of the bacterial profile both in gills and seawater for alpha and beta diversities respectively. The functional prediction analysis highlighted an overexpression of human gut-associated bacteria in relation to the season-related increase in seawater temperature.

Conclusions
These findings enhance our understanding of the differences between gill-associated and seawater microbiota composition and provide novel insights into the functions carried out by bacteria inhabiting these niches, as well as on the key host-symbiont relationships of bivalves in lagoon environments.
Inborn errors of immunity in adulthood
Authors: Wang Joanne J. F. , Dhir Arün , Hildebrand Kyla J. , Turvey Stuart E. , Schellenberg Robert , Chen Luke Y. C. , Pourshahnazari Persia , Biggs Catherine M. 
Published: January 2024

AbstractInborn errors of immunity (IEIs) are a group of conditions whereby parts of the immune system are missing or dysfunctional. Once thought to primarily be a pediatric disorder, it is now estimated that more than 50% of worldwide incident IEI cases are accounted for by adults. Delayed diagnosis, late symptom onset, and IEI phenocopies can all lead to adult-onset recognition of IEIs. Lack of awareness regarding the diversity of IEI manifestations in adults contributes to diagnostic and treatment delays. Prompt referral to immunology is critical so that patients can receive a precise molecular diagnosis and targeted therapy when available. This article serves as a primer on IEIs in adulthood, highlighting the pathophysiology, epidemiology and clinical features. We present clinical vignettes of three key IEIs to assist clinicians in building illness scripts on their presentations. We provide a framework for the laboratory evaluation of IEIs and their initial treatment, with the aim of improving recognition and management of these conditions.
Low dose lofexidine for medically directed outpatient opioid tapering in adults with chronic pain: a prospective case series
Authors: Ellis Megan M. , Eberhart Nathan D. , Warner Nafisseh S. , Hooten W. Michael 
Published: January 2024

Abstract
Background
In adults with chronic pain, mild-to-moderate withdrawal symptoms during medically directed opioid tapering in the outpatient setting may not be accompanied by hypertension or tachycardia. This clinical scenario could limit the use of lofexidine at dosages reported in clinical trials of opioid withdrawal precipitated by abrupt opioid discontinuation. Thus, the primary aim of this prospective case series is to describe the use of low dose lofexidine for opioid withdrawal in patients with chronic pain undergoing medically directed opioid tapering in an outpatient setting.

Methods
Six patients (white 5, Latino 1) admitted to an outpatient interdisciplinary pain rehabilitation program met inclusion and exclusion criteria. Patients self-selected to undergo medically directed opioid tapering, and the medication the patients were prescribed upon admission was used in the taper schedule. Upon initiation of the opioid taper, patients received 0.18 mg of lofexidine every 6 hours.

Results
Five of the six patients were women, and the median morphine milligram equivalents at baseline were 36.9. The median taper duration was 15 days, and the median duration of lofexidine administration was 14 days. Withdrawal scores were mild throughout the taper in four patients, and two patients with fibromyalgia experienced single episodes of moderately severe withdrawal symptoms at the median morphine milligram equivalent midpoint of the taper. No hypotension or sustained bradycardia were observed, and no adverse effects related to lofexidine were reported.

Conclusion
The observations from this prospective case series suggest that low-dose lofexidine may be a feasible adjunct medication to attenuate withdrawal symptoms in adults with chronic pain undergoing outpatient opioid tapering.