bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered Bacteria-Based Living Materials for Biotherapeutic Applications
Authors: Omer Rabia , Mohsin Muhammad Zubair , Mohsin Ali , Mushtaq Bilal Sajid , Huang Xumeng , Guo Meijin , Zhuang Yingping , Huang Jiaofang 
Published: November 2022

Future advances in therapeutics demand the development of dynamic and intelligent living materials. The past static monofunctional materials shall be unable to meet the requirements of future medical development. Also, the demand for precision medicine has increased with the progressively developing human society. Therefore, engineered living materials (ELMs) are vitally important for biotherapeutic applications. These ELMs can be cells, microbes, biofilms, and spores, representing a new platform for treating intractable diseases. Synthetic biology plays a crucial role in the engineering of these living entities. Hence, in this review, the role of synthetic biology in designing and creating genetically engineered novel living materials, particularly bacteria, has been briefly summarized for diagnostic and targeted delivery. The main focus is to provide knowledge about the recent advances in engineered bacterial-based therapies, especially in the treatment of cancer, inflammatory bowel diseases, and infection. Microorganisms, particularly probiotics, have been engineered for synthetic living therapies. Furthermore, these programmable bacteria are designed to sense input signals and respond to disease-changing environments with multipronged therapeutic outputs. These ELMs will open a new path for the synthesis of regenerative medicines as they release therapeutics that provide in situ drug delivery with lower systemic effects. In last, the challenges being faced in this field and the future directions requiring breakthroughs have been discussed. Conclusively, the intent is to present the recent advances in research and biomedical applications of engineered bacteria-based therapies during the last 5 years, as a novel treatment for uncontrollable diseases.
A requirement for Krüppel Like Factor‐4 in the maintenance of endothelial cell quiescence
Authors: Mastej Victoria , Axen Cassondra , Wary Anita , Minshall Richard D. , Wary Kishore K. 
Published: November 2022

Rationale and Goal: Endothelial cells (ECs) are quiescent and critical for maintaining homeostatic functions of the mature vascular system, while disruption of quiescence is at the heart of endothelial to mesenchymal transition (EndMT) and tumor angiogenesis. Here, we addressed the hypothesis that KLF4 maintains the EC quiescence.Methods and Results: In ECs, KLF4 bound to KLF2, and the KLF4-transctivation domain (TAD) interacted directly with KLF2. KLF4-depletion increased KLF2 expression, accompanied by phosphorylation of SMAD3, increased expression of alpha-smooth muscle actin (αSMA), VCAM-1, TGF-β1, and ACE2, but decreased VE-cadherin expression. In the absence of Klf4, Klf2 bound to the Klf2-promoter/enhancer region and autoregulated its own expression. Loss of EC-Klf4 in RosamT/mG::Klf4fl/fl::Cdh5CreERT2 engineered mice, increased Klf2 levels and these cells underwent EndMT. Importantly, these mice harboring EndMT was also accompanied by lung inflammation, disruption of lung alveolar architecture, and pulmonary fibrosis.Conclusion: In quiescent ECs, KLF2 and KLF4 partnered to regulate a combinatorial mechanism. The loss of KLF4 disrupted this combinatorial mechanism, thereby upregulating KLF2 as an adaptive response. However, increased KLF2 expression overdrives for the loss of KLF4, giving rise to an EndMT phenotype.
Repair effect of the poly (D,L-lactic acid) nanoparticle containing tauroursodeoxycholic acid-eluting stents on endothelial injury after stent implantation
Authors: Zhou Jiedong , Weng Jingfan , Huang Xingxiao , Sun Shimin , Yang Qi , Lin Hui , Yang Jinjin , Guo Hangyuan , Chi Jufang 
Published: November 2022

BackgroundChronic endoplasmic reticulum stress (ERS) plays a crucial role in cardiovascular diseases. Thus, it can be considered a therapeutic target for these diseases. In this study, poly (D,L-lactic acid) (PDLLA) nanoparticle-eluting stents loaded with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, was fabricated to assess their ability to reduce endothelial cell apoptosis and promote re-endothelialization after stent implantation.Materials and methodsPDLLA nanoparticles loaded with TUDCA were prepared via the emulsification-solvent evaporation method. The cumulative release rates of TUDCA were measured in vitro via high-performance liquid chromatography. The carotid arteries of rabbits were subsequently implanted with stents in vivo. The rabbits were then sacrificed after 4 weeks for scanning electron microscopy. Meanwhile, TUDCA concentration in the homogenate of the peripheral blood and distal vascular tissue after stent implantation was measured. The effect of TUDCA on ERS, apoptosis, and human umbilical vein endothelial cell (HUVEC) function was investigated in vitro by performing cell migration assay, wound healing assay, cell proliferation assays, endoplasmic reticulum (ER)-specific fluorescence staining, immunofluorescence, and western blotting.ResultsTUDCA nanoparticles were released slowly over 28 days. In addition, TUDCA-eluting stents enhanced re-endothelialization and accelerated the recovery of endotheliocytes in vivo. ERS and apoptosis significantly increased in H2O2-treated HUVECs in vitro. Meanwhile, TUDCA reduced apoptosis and improved function by inhibiting ERS in H2O2-treated HUVECs. Decreased rates of apoptosis and ERS were observed after silencing XBP-1s in H2O2-treated HUVECs.ConclusionTUDCA can inhibit apoptosis and promote re-endothelialization after stent implantation by inhibiting IRE/XBP1s-related ERS. These results indicate the potential therapeutic application of TUDCA as a drug-coated stent.
Global research trends in in-stent neoatherosclerosis: A CiteSpace-based visual analysis
Authors: Wang Heng , Wang Qian , Hu Jie , Zhang Ruijing , Gao Tingting , Rong Shuling , Dong Honglin 
Published: November 2022

BackgroundRecent studies have shown that in-stent neoatherosclerosis (ISNA/NA) is an important cause of late stent failure. A comprehensive understanding of the current state of research in this field will facilitate the analysis of its development trends and hot frontiers. However, no bibliometric correlation has been reported yet. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights.MethodsPublications were collected from the Web of Science Core Collection (WoSCC) and PubMed. Microsoft Excel, SPSS and CiteSpace were used to analyze and present the data.ResultsA total of 498 articles were collected, with Japan and Cardiovasc Res Fdn being the main publishing forces in all country/region and institutions. J AM COLL CARDIOL is the journal with the most published and co-cited articles. According to co-citation analysis, optical coherence tomography, thrombosis, implantation, restenosis, drug-eluting stent, and bare metal stent have become more and more popular recently.ConclusionISNA is a niche and emerging field. How to reduce the incidence of ISNA and improve the late patency rate of coronary stents may remain a hot spot for future research. The pathogenesis of ISNA also needs to be explored in more depth.
Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis
Authors: Li Sicong , He Jinshan , Zhang Xinyi , Cai Yuchun , Liu Jian , Nie Xiaoyan , Shi Luwen 
Published: November 2022

ObjectiveThe aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis.Materials and methodsThree databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets.ResultsPatients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29]), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28]), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above.ConclusionCML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.
Expansion/shrinkage history of the Paratethys Sea during the Eocene: New insights from eolian Red Clay records in the Altyn Mountains, northern China
Authors: Guo Benhong , Nie Junsheng , Li Jianxing , Xiao Wenjiao , Pan Feng 
Published: November 2022

Uplift of the Tibetan Plateau, expansion/shrinkage of the Paratethys Sea, and global climate are three major forcings for central-east Asian climatic and environmental variations during the Cenozoic. However, knowledge of expansion/shrinkage history of the Paratethys Sea is much less well known in comparison with the other two forcings. Here, we present a first multiple-parameter environmental magnetic and diffuse reflectance spectroscopy study of the Eocene eolian Red Clay deposits (∼51–40 Ma) in the Xorkol Basin of the northeastern Tibetan Plateau, which is near the easternmost maximum boundary of the Eocene Paratethys Sea. The first detailed Eocene expansion/shrinkage history of the Paratethys Sea was reconstructed based on the hematite content of the Eocene Red Clay, which shows remarkable consistency with the previous low-resolution Paratethys Sea paleowater depth record in the southwestern Tarim Basin. These results demonstrate that the Paratethys Sea experienced a three-stage (shrinkage-expansion-shrinkage) evolution between ∼51 and 40 Ma, with boundaries at ∼46.2 and 42 Ma. Superimposed on this framework, the Paratethys Sea experienced four times of rapid shrinkages at the expansion phase (shows 400-kyr cycles) during ∼44–42 Ma modulated by eccentricity forcings. These new results are of great significance to evaluate respective role of Tibetan uplift, global climate, and Paratethys Sea area variations in Asian climate and environmental change over the Eocene.
Numerical Study on the performance of a heat pump-driven-DCMD for sustainable desalination
Authors: Oh Seung Jin , Kim Yeongmin , Hong Youngsun , Kim Jong Woo , Kang Byungchan 
Published: November 2022

The study presents an energy-efficient desalination system that combines direct contact membrane distillation (DCMD) and a heat pump to improve thermal efficiency and integrate with photovoltaics. DCMD is a sort of thermal desalination process, and it requires a lot of thermal energy. A heat pump is a device that produces both hot and cold energy simultaneously with less electrical energy input compared to other heating devices, such as a boiler and an electrical heater. A hollow-fiber DCMD and a 10-kW water-to-water heat pump were considered for a numerical simulation in this study. Numerical models were established for each device and validated against the results obtained from the literature. The simulation was first carried out to identify the performance of the system based on the baseline. After that, a series of simulations were carried out in order to investigate the performance of the proposed system in terms of specific energy consumption (SEC), gained output ratio (GOR), and the coefficient of performance (COP) under various operating conditions. Results showed that the minimum SEC and the maximum GOR were achieved at the inlet feed water temperature of 66.5°C with a mass flow rate of 20 kg/min and the inlet permeate temperature of 19.8°C with a mass flow rate of 10 lpm. On the other hand, it was found that the maximum COP can be observed at the inlet feed water temperature of 23.6°C with a mass flow rate of 10 lpm and at the inlet permeate temperature of 8.9°C with a mass flow rate of 20 lpm.
The advanced lung cancer inflammation index predicts chemotherapy response and infection risk in multiple myeloma patients receiving induction chemotherapy
Authors: Cheng Jie , Li Qianyuan , Xiao Sheng , Nie Lu , Liao Jianping , Jiang Qingjie , Xiang Biyu , Zhang Hongfei , Jiang Yanhong , Yao Chenjiao 
Published: November 2022

Objective: This study aims to determine the clinical significance of the advanced lung cancer inflammation index (ALI) in predicting prognosis, chemotherapy response, and infection risk in newly diagnosed multiple myeloma (MM) patients receiving induction therapy.Methods: A retrospective analysis of the clinical characteristics and laboratory data of 111 newly diagnosed MM patients from the Haematology Department of the Third Xiangya Hospital of Central South University from January 2014 to March 2020 was performed. We first determined the relationship between ALI and overall survival (OS), as well as clinical and laboratory parameters. Second, predictive factors for chemotherapy response were analysed by univariate and multivariate regression analyses. Third, univariate regression analysis of risk factors was performed using infection as the evaluable outcome.Results: Of the 111 evaluable patients, the low ALI group (&lt;32.7) exhibited significantly poorer survival than the high ALI group (51 months versus 77 months). Multivariable analysis showed that advanced age, chemotherapy response and serum calcium level were independent prognostic factors for OS. Better chemotherapy efficacy in the high ALI group (89.3%) than in the low ALI group (42.2%) (p &lt; 0.001) was noted. Multivariate analysis suggested that only ALI [HR: 0.110, 95% CI (0.035–0.350), p = 0.000] is an independent predictive factor in evaluating the efficiency of induction chemotherapy. Forty patients (36.04%) presented with infection after induction chemotherapy. Univariate analysis suggested that low ALI and abnormal renal function increase risk of infection in newly diagnosed MM patients.Conclusion: Our study confirmed that ALI is not only a prognostic biomarker for newly diagnosed patients, but also predicts chemotherapy efficacy in newly diagnosed MM patients receiving induction therapy.
Fibroblast growth factor receptor family mutations as a predictive biomarker for immune checkpoint inhibitors and its correlation with tumor immune microenvironment in melanoma
Authors: Zhang Wengang , Xia Handai , Yang Rui , Zhang Yuqing , Zheng Qi , Shang Xiaoling , Liu Ni , Ma Xinchun , Wei Chenxi , Chen Hang , Mu Xin , Wang Xiuwen , Liu Yanguo 
Published: November 2022

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) has significantly improved the clinical outcomes of patients with metastatic melanoma. However, survival benefits are only observed in a subset of patients. The fibroblast growth factor receptor (FGFR) family genes are frequently mutated in melanoma, yet their impacts on the efficacy of ICIs remain unclear. Our study aimed to explore the association of FGFR mutations with ICIs efficacy in metastatic melanoma.MethodsThe Cancer Genome Atlas (TCGA) data (PanCancer Atlas, skin cutaneous melanoma (SKCM), n = 448) in cBioPortal were collected as a TCGA cohort to investigate the association between FGFR mutations and prognosis of melanoma patients. To explore the impact of FGFR mutations on the efficacy of ICIs in melanoma, clinical and tumor whole-exome sequencing (WES) data of four ICI-treated studies from cBioPortal were consolidated as an ICIs-treated cohort. Moreover, the relationship between FGFR mutations and immunogenicity (tumor mutation burden (TMB), neo-antigen load (NAL), mismatch repair (MMR)-related genes and DNA damage repair (DDR)-related genes) of melanoma was evaluated utilizing data from the ICIs-treated cohort. The influence of FGFR mutations on the tumor immune microenvironment (TIME) of melanoma was also analyzed using the TCGA cohort.ResultsIn the TCGA cohort, survival in melanoma patients with or without FGFR mutations was nearly equivalent. In the ICIs-treated cohort, patients with FGFR mutations had better survival than those without (median overall survival: 60.00 vs. 31.00 months; hazard ratio: 0.58, 95% CI: 0.42-0.80; P = 0.0051). Besides, the objective response rate was higher for patients harboring FGFR mutations (55.56%) compared to wild-type patients (22.40%) (P = 0.0076). Mechanistically, it was revealed that FGFR mutations correlated with increased immunogenicity (e.g., TMB, NAL, MMR-related gene mutations and DDR-related gene mutations). Meanwhile, FGFR mutant melanoma tended to exhibit an enhanced antitumor TIME compared with its wild-type counterparts.ConclusionsOur study demonstrated that FGFR mutations is a promising biomarker in stratifying patients with advanced melanoma who might benefit from ICIs therapy.
Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study
Authors: Serrano-Villar Sergio , Cohen Calvin , Baker Jason V. , Janeiro Maria João , Aragão Filipa , Melbourne Kathleen , Gonzalez Jose Luis , Lara Laura , Kim Connie , Moreno Santiago 
Published: November 2022

IntroductionVariable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS events (SNAEs)/death by changes in interleukin-6 (IL-6) and D-dimer, we modeled the effects of differences in these markers between specific ART regimens on the long-term risk of clinical outcomes.MethodsWe used a Markov model to compare the risk of SNAEs/death with differences in IL-6 and D-dimer levels associated with remaining on specific three-drug regimens versus switching to specific two-drug ART regimens over 5 years of treatment. We used IL-6 and D-dimer data based on trajectories over time from the randomized TANGO and observational AIR studies. Age at model entry was set at 39 years. The primary endpoint was the number needed to treat for one additional SNAE/death.ResultsOver 3 years, PWH on one of the three-drug regimens studied were predicted to spend 13% more time in the low IL-6 quartile and 11% less time in the high IL-6 quartile compared with those on one of the two-drug regimens. Over 3 years, the predicted mean number of SNAEs/deaths per 100 PWH was 6.58 for a three-drug regimen associated with lower IL-6 levels versus 6.90 for a two-drug regimen associated with higher IL-6 levels. The number needed to treat for one additional SNAE/death among PWH receiving a two-drug versus three-drug regimen for 3 years was 81. Approximately 7,500 participants would be required for a 5-year clinical study to evaluate the accuracy of the model.ConclusionsOur Markov model suggests that higher IL-6 levels associated with switching from specific three- to two- drug ART regimens may be associated with an increase in the risk of SNAEs/death. Clinical studies are warranted to confirm or refute these results.
Dynamic changes of otolith organ function before and after repositioning in patients with benign paroxysmal positional vertigo detected by virtual reality auxiliary technology: A cohort study
Authors: Zhao Chunjie , Yang Qingjun , Song Jijun 
Published: November 2022

ObjectivesTo dynamically investigate otolith function in patients with benign paroxysmal positional vertigo (BPPV) before, after, and 1 month after repositioning, and explore the possible compensation mechanisms.MethodsThirty-six patients confirmed with BPPV (canal lithiasis) treated in our hospital between August 2020 and March 2021, as well as 36 health controls matched for age and gender (normal control group, NC group) were enrolled. For NC group, the virtual reality (VR) auxiliary static subjective visual vertical (SVV), subjective visual horizontal (SVH), and SVV of dynamic unilateral centrifugation (DUC), were measured at inclusion. For the BPPV group, visual analog scale (VAS) was used to assess the vertigo degree, while static SVV, SVH, and DUC were performed before, after, and 1 month after repositioning. First, we compare the deviations of SVV0/SVH0° when the subject's head is in the positive position, and SVV of DUC between BPPV and NC groups before repositioning, after which we compared the deviations in SVV45, SVV90, SVH45, SVH90°, and SVV of DUC between the affected and unaffected sides before repositioning. Finally, paired t-test was used to compare the VAS score, deviations in static SVV0, SVV45, SVV90, SVH0, SVH45, and SVH90°, and deviations in SVV of DUC before, after, and 1 month after repositioning. (Here, 0, 45, and 90° refer to the angle which the center axis of head deviates from the gravity line.)ResultsSVV0 SVH0°, and SVV of DUC at 120 and 180°/s 0 significantly differed between BPPV and NC group before repositioning. The deviations in SVV45, SVV90, SVH45, SVH90°, and SVV of DUC at 120°/s-2 and 180°/s-4.5 did not significantly differ between bilateral sides in BPPV patients before repositioning. The deviation in SVH90° was significantly lower after repositioning than before. The deviation in SVH45° was significantly higher 1 month after repositioning than before. The deviation angle of SVV of DUC at 180°/s-0 was significantly lower after repositioning than before. The vertigo VAS score of patient with BPPV continued to decrease after repositioning.ConclusionBefore repositioning, the otolithic organ function of BPPV patients was obviously impaired, with no significant difference between the healthy and affected ear. After repositioning, there was a transient recovery of otolithic organ dysfunction followed by a sustained decline to similar levels to before repositioning.