bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic characterization of a novel Salinicola salarius isolate applied for the bioconversion of agro-industrial wastes into polyhydroxybutyrate
Authors: Abdelrahman Shymaa A. , Barakat Olfat S. , Ahmed Marwa N. 
Published: February 2024

Abstract
Background
Polyhydroxybutyrate (PHB) has emerged as a promising eco-friendly alternative to traditional petrochemical-based plastics. In the present study, we isolated and characterized a new strain of Salinicola salarius, a halophilic bacterium, from the New Suez Canal in Egypt and characterized exclusively as a potential PHB producer. Further genome analysis of the isolated strain, ES021, was conducted to identify and elucidate the genes involved in PHB production.

Results
Different PHB-producing marine bacteria were isolated from the New Suez Canal and characterized as PHB producers. Among the 17 bacterial isolates, Salinicola salarius ES021 strain showed the capability to accumulate the highest amount of PHB. Whole genome analysis was implemented to identify the PHB-related genes in Salinicola salarius ES021 strain. Putative genes were identified that can function as phaCAB genes to produce PHB in this strain. These genes include fadA, fabG, and P3W43_16340 (encoding acyl-CoA thioesterase II) for PHB production from glucose. Additionally, phaJ and fadB were identified as key genes involved in PHB production from fatty acids. Optimization of environmental factors such as shaking rate and incubation temperature, resulted in the highest PHB productivity when growing Salinicola salarius ES021 strain at 30°C on a shaker incubator (110 rpm) for 48 h. To maximize PHB production economically, different raw materials i.e., salted whey and sugarcane molasses were examined as cost-effective carbon sources. The PHB productivity increased two-fold (13.34 g/L) when using molasses (5% sucrose) as a fermentation media. This molasses medium was used to upscale PHB production in a 20 L stirred-tank bioreactor yielding a biomass of 25.12 g/L, and PHB of 12.88 g/L. Furthermore, the produced polymer was confirmed as PHB using Fourier-transform infrared spectroscopy (FTIR), gas chromatography-mass spectroscopy (GC–MS), and nuclear magnetic resonance spectroscopy (NMR) analyses.

Conclusions
Herein,Salinicola salarius ES021 strain was demonstrated as a robust natural producer of PHB from agro-industrial wastes. The detailed genome characterization of the ES021 strain presented in this study identifies potential PHB-related genes. However, further metabolic engineering is warranted to confirm the gene networks required for PHB production in this strain. Overall, this study contributes to the development of sustainable and cost-effective PHB production strategies.
Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications
Authors: Cheng Bingjie , Yu Keyang , Weng Xing , Liu Zhaojun , Huang Xuewu , Jiang Yuhong , Zhang Shuai , Wu Shuyan , Wang Xiaoyuan , Hu Xiaoqing 
Published: February 2024

Abstract
Background
Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities.

Results
Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage.

Conclusions
Two novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.
TRP channels associated with macrophages as targets for the treatment of obese asthma
Authors: Zhu Wenzhao , Bai Dinxi , Ji Wenting , Gao Jing 
Published: February 2024

AbstractGlobally, obesity and asthma pose significant health challenges, with obesity being a key factor influencing asthma. Despite this, effective treatments for obese asthma, a distinct phenotype, remain elusive. Since the discovery of transient receptor potential (TRP) channels in 1969, their value as therapeutic targets for various diseases has been acknowledged. TRP channels, present in adipose tissue cells, influence fat cell heat production and the secretion of adipokines and cytokines, which are closely associated with asthma and obesity. This paper aims to investigate the mechanisms by which obesity exacerbates asthma-related inflammation and suggests that targeting TRP channels in adipose tissue could potentially suppress obese asthma and offer novel insights into its treatment.
Phosphorylation: new star of pathogenesis and treatment in steatotic liver disease
Authors: Lv Tiansu , Lou Yan , Yan Qianhua , Nie Lijuan , Cheng Zhe , Zhou Xiqiao 
Published: February 2024

AbstractSteatotic liver disease poses a serious threat to human health and has emerged as one of the most significant burdens of chronic liver disease worldwide. Currently, the research mechanism is not clear, and there is no specific targeted drug for direct treatment. Phosphorylation is widely regarded as the most common type of protein modification, closely linked to steatotic liver disease in previous studies. However, there is no systematic review to clarify the relationship and investigate from the perspective of phosphorylation. Phosphorylation has been found to mainly regulate molecule stability, affect localization, transform molecular function, and cooperate with other protein modifications. Among them, adenosine 5’-monophosphate-activated protein kinase (AMPK), serine/threonine kinase (AKT), and nuclear factor kappa-B (NF-kB) are considered the core mechanisms in steatotic liver disease. As to treatment, lifestyle changes, prescription drugs, and herbal ingredients can alleviate symptoms by influencing phosphorylation. It demonstrates the significant role of phosphorylation as a mechanism occurrence and a therapeutic target in steatotic liver disease, which could be a new star for future exploration.
The war on drugs is a war on us: young people who use drugs and the fight for harm reduction in the Global South
Authors: Stowe M-J , Gatonye Rita , Maharjan Ishwor , Kehinde Seyi , Arya Sidarth , Valderrábano Jorge Herrera , Mcbride Angela , Scheibein Florian , Igonya Emmy Kageha , Fast Danya 
Published: February 2024

AbstractIn the Global South, young people who use drugs (YPWUD) are exposed to multiple interconnected social and health harms, with many low- and middle-income countries enforcing racist, prohibitionist-based drug policies that generate physical and structural violence. While harm reduction coverage for YPWUD is suboptimal globally, in low- and middle-income countries youth-focused harm reduction programs are particularly lacking. Those that do exist are often powerfully shaped by global health funding regimes that restrict progressive approaches and reach. In this commentary we highlight the efforts of young people, activists, allies, and organisations across some Global South settings to enact programs such as those focused on peer-to-peer information sharing and advocacy, overdose monitoring and response, and drug checking. We draw on our experiential knowledge and expertise to identify and discuss key challenges, opportunities, and recommendations for youth harm reduction movements, programs and practices in low- to middle-income countries and beyond, focusing on the need for youth-driven interventions. We conclude this commentary with several calls to action to advance harm reduction for YPWUD within and across Global South settings.
Understanding immune microenvironment alterations in the brain to improve the diagnosis and treatment of diverse brain diseases
Authors: Xu Xiaotong , Han Yi , Zhang Binlong , Ren Quanzhong , Ma Juan , Liu Sijin 
Published: February 2024

AbstractAbnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.
Engineered bone marrow mesenchymal stem cell-derived exosomes loaded with miR302 through the cardiomyocyte specific peptide can reduce myocardial ischemia and reperfusion (I/R) injury
Authors: Gu Jianjun , You Jia , Liang Hao , Zhan Jiacai , Gu Xiang , Zhu Ye 
Published: February 2024

Abstract
Background
MicroRNA (miRNA)-based therapies have shown great potential in myocardial repair following myocardial infarction (MI). MicroRNA-302 (miR302) has been reported to exert a protective effect on MI. However, miRNAs are easily degraded and ineffective in penetrating cells, which limit their clinical applications. Exosomes, which are small bioactive molecules, have been considered as an ideal vehicle for miRNAs delivery due to their cell penetration, low immunogenicity and excellent stability potential. Herein, we explored cardiomyocyte-targeting exosomes as vehicles for delivery of miR302 into cardiomyocyte to potentially treat MI.

Methods
To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered exosomes with cardiomyocyte specific peptide (CMP, WLSEAGPVVTVRALRGTGSW). Afterwards, the engineered exosomes were characterized and identified using transmission electron microscope (TEM) and Nanoparticle Tracking Analysis (NTA). Later on, the miR302 mimics were loaded into the engineered exosomes via electroporation technique. Subsequently, the effect of the engineered exosomes on myocardial ischemia and reperfusion (I/R) injury was evaluated in vitro and in vivo, including MTT, ELISA, real-time quantitative polymerase chain reaction (PCR), western blot, TUNNEL staining, echocardiogram and hematoxylin and eosin (HE) staining.

Results
Results of in vitro experimentation showed that DSPE-PEG-CMP-EXO could be more efficiently internalized by H9C2 cells than unmodified exosomes (blank‐exosomes). Importantly, compared with the DSPE-PEG-CMP-EXO group, DSPE-PEG-CMP-miR302-EXO significantly upregulated the expression of miR302, while exosomes loaded with miR302 could enhance proliferation of H9C2 cells. Western blot results showed that the DSPE-PEG-CMP-miR302-EXO significantly increased the protein level of Ki67 and Yap, which suggests that DSPE-PEG-CMP-miR302-EXO enhanced the activity of Yap, the principal downstream effector of Hippo pathway. In vivo, DSPE-PEG-CMP-miR302-EXO improved cardiac function, attenuated myocardial apoptosis and inflammatory response, as well as reduced infarct size significantly.

Conclusion
In conclusion, our findings suggest that CMP-engineered exosomes loaded with miR302 was internalized by H9C2 cells, an in vitro model for cardiomyocytes coupled with potential enhancement of the therapeutic effects on myocardial I/R injury.
Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes
Authors: Kodosaki Eleftheria , Watkins W. John , Loveless Sam , Kreft Karim L. , Richards Aidan , Anderson Valerie , Hurler Lisa , Robertson Neil P. , Zelek Wioleta M. , Tallantyre Emma C. 
Published: February 2024

AbstractEstablishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and significantly improved the prediction of the development of sustained disability in multiple sclerosis. Serum models rivalled those of cerebrospinal fluid, holding promise for a non-invasive approach. The utility of our biomarker models can only be established by robust validation in different and varied cohorts.
Effective density of inhaled environmental and engineered nanoparticles and its impact on the lung deposition and dosimetry
Authors: Lizonova Denisa , Nagarkar Amogh , Demokritou Philip , Kelesidis Georgios A. 
Published: February 2024

Abstract
Background
Airborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρb, rather than the effective density, ρeff. This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location.

Results
Here, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρeff which was found to be up to one order of magnitude smaller than ρb. Accounting for the realistic ρeff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρeff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon.

Conclusions
The doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρb is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρeff, which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health.

Graphical abstract
The efficacy and safety of corticotomy and periodontally accelerated osteogenic orthodontic interventions in tooth movement: an updated meta-analysis
Authors: Zhou Huan , Zhang Yi-Fan , Qi Yan-Xin , Zhang Qian-Qian , Liu Na , Chen Yue 
Published: February 2024

Abstract
Background
The surgically facilitated orthodontic strategy has been a promising strategy for orthodontic treatment recently. Therefore, the present meta-analysis was conducted to assess the available scientific evidence regarding the clinical outcomes, including the potential detrimental effects associated with these surgical procedures, with the aim of providing much more evidence-based information for clinical practice.

Methods
An electronic search of three databases (PubMed, Cochrane, and Embase) and a manual search of relevant articles published up to May 2023 were carried out. Clinical trials (≥ 10 subjects) that utilized surgically facilitated orthodontic strategies with clinical and/or radiographic outcomes were included. Meta-analyses and sub-group analyses were performed to analyze the standardized mean difference (SMD) or weighted mean difference (WMD), and confidence interval (CI) for the recorded variables.

Results
Nineteen studies published from Oct 2012 to May 2023 met the inclusion criteria. Based on the analysis outcomes, corticotomy treatment significantly decreased the alignment duration (WMD: -1.08 months; 95% CI = -1.65, -0.51 months, P = 0.0002), and accelerated the canine movement (WMD: 0.72 mm; 95% CI = 0.63, 0.81 mm, P < 0.00001) compared to the traditional orthodontic group. The periodontally accelerated osteogenic orthodontic (PAOO) strategy markedly reduced the total treatment duration (SMD: -1.98; 95% CI = -2.59, -1.37, P < 0.00001) and increased the bone thickness (SMD:1.07; 95% CI = 0.74, 1.41, P < 0.00001) compared to traditional orthodontic treatment.

Conclusion
The present study suggests that facilitated orthodontic treatment in terms of corticotomy and PAOO strategy may represent attractive and effective therapeutic strategy for orthodontic patients.
Reliability of landmark identification for analysis of the temporomandibular joint in real-time MRI
Authors: Mouchoux Jérémy , Meyer-Marcotty Philipp , Sojka Florian , Dechent Peter , Klenke Daniela , Wiechens Bernhard , Quast Anja 
Published: February 2024

Abstract
Background
Real-time magnetic resonance imaging (rtMRI) is essential for diagnosing and comprehending temporomandibular joint (TMJ) movements. Current methods for tracking and analysis require manual landmark placement on each acquisition frame. Therefore, our study aimed to assess the inter- and intra-rater reliability of placing cephalometric landmarks in frames from a dynamic real-time TMJ MRI.

Material and methods
Four real-time MRIs of the right TMJ were taken during mandibular movement at ten frames per second. Seven dentists identified ten landmarks on two frames (intercuspal position—ICP—and maximum mouth opening—MMO) twice at a two-week interval, yielding 112 tracings. Six typical cephalometric measurements (angles and distances) were derived from these landmarks. The reliabilities of landmarks and measurements were evaluated using distance-based (dbICC), linear mixed effect model intraclass correlation (lmeICC), and standard ICC.

Results
The average inter-rater reliability for the landmarks stood at 0.92 (dbICC) and 0.93 (lmeICC). The intra-rater reliability scores were 0.97 and 0.98. Over 80% of the landmarks showed an ICC greater than 0.98 (inter-rater) and over 0.99 (intra-rater). The lowest landmark ICC was observed for the orbitale and the oblique ridge of the mandibular ramus. However, the cephalometric angle and distance measurements derived from these landmarks showed only moderate to good reliability, whereas the reliability in the frames with ICP was better than those with MMO. Measurements performed in the ICP frame were more reliable than measurements in the MMO frame.

Conclusion
While dentists reliably localize isolated landmarks in real-time MRIs, the cephalometric measurements derived from them remain inconsistent. The better results in ICP than MMO are probably due to a more familiar jaw position. The higher error rate of the TMJ measurements in MMO could be associated with a lack of training in real-time MRI analysis in dentistry.