Life cycle assessment of bio-based levoglucosan production from cotton straw through fast pyrolysis

This study aimed to evaluate the environmental impacts (i.e. global warming potential (GWP) and resource depletion (RD)) of the bio-based levoglucosan production process through fast pyrolysis of cotton straw via life cycle assessment (LCA). An LCA model consisting of feedstock transportation, biomass pretreatment, fast pyrolysis, bio-oil transportation, bio-oil recovery and levoglucosan extraction was developed. Results indicated that GWP and RD of bio-based levoglucosan production were approximately 2 and 32.5 times less than that of the petroleum-based counterpart. Sensitivity analysis showed that the GWP and RD of levoglucosan production were highly sensitive to plant size, hydrochloric acid usage, cooling energy, levoglucosan yield and bio-oil yield. The results of this research could provide a framework for robust decision making at an industrial level, which is useful for the commercial-scale production of levoglucosan

Blockade of FGF2/FGFR2 Partially Overcomes Bone Marrow Mesenchymal Stromal Cells Mediated Progression of T-cell Acute Lymphoblastic Leukaemia

The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the effects of bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilaterally with leukaemia cells, leading to ALL progression. In order to find MSCs-based microenvironment targeted therapeutic strategies, Notch1-induced T-cell ALL (T-ALL) mice models were used and dynamic alterations of BM-MSCs with increased cell viability during T-ALL development was observed. In T-ALL mice derived stroma-based condition, leukaemia cells showed significantly elevated growth capacity indicating that MSCs participated in leukaemic niche formation. RNA sequence results revealed that T-ALL derived MSCs secreted fibroblast growth factor 2 (FGF2), which combined with fibroblast growth factor receptor 2 (FGFR2) on leukaemia cells, resulting in activation of PI3K/AKT/mTOR signalling pathway in leukaemia cells. In vitro blocking the interaction between FGF2 and FGFR2 with BGJ398 (infigratinib), a FGFR1-3 kinase inhibitor, or knockdown FGF2 in MSCs by interference caused deactivation of PI3K/AKT/mTOR pathway and dysregulations of genes associated with cell cycle and apoptosis in ALL cells, leading to decrease of leukaemia cells. In mouse model received BGJ398, overall survival was extended and dissemination of leukaemia cells in BM, spleen, liver and peripheral blood was decreased. After subcutaneous injection of primary human T-ALL cells with MSCs, tumour growth was suppressed when FGF2/FGFR2 was interrupted. Thus, inhibition of FGF2/FGFR2 interaction appears to be a valid strategy to overcome BM-MSCs mediated progression of T-ALL, and BGJ398 could indeed improve outcomes in T-ALL, which provide theoretical basis of BGJ398 as a BM microenvironment based therapeutic strategy to control disease progression

Progress of immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma

Among primary liver cancers, hepatocellular carcinoma is the most common pathological type. Its onset is insidious, and most patients have no obvious discomfort in the early stage, so it is found late, and the opportunity for surgical radical treatment is lost, resulting in a poor prognosis. With the introduction of molecular-targeted drugs represented by sorafenib, patients with middle- and late-stage liver cancer have regained the light of day. However, their therapeutic efficacy is relatively low due to the limited target of drug action, toxic side effects, and other reasons. At this time, the emergence of immunotherapy represented by immune checkpoint inhibitors (ICIs) well breaks this embarrassing situation, which mainly achieves the anti-tumor purpose by improving the tumor immune microenvironment. Currently, ICI monotherapy, as well as combination therapy, has been widely used in the clinic, further prolonging the survival of patients with advanced hepatocellular carcinoma. This article reviews the development of monotherapy and combination therapy for ICIs in advanced hepatocellular carcinoma and the latest research progress

Expert consensus on digital intraoral scanning technology

Digital intraoral scanning is a hot topic in the field of oral digital technology. In recent years, digital intraoral scanning has gradually become the mainstream technology in orthodontics, prosthodontics, and implant dentistry. The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression. However, the operators are less familiar with the intraoral scanning characteristics, imaging processing, operator scanning method, oral tissue specificity of the scanned object, and restoration design. Thus far, no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad. To deal with the problems encountered in oral scanning and improve the quality of digital scanning, we collected common expert opinions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence. We also describe the scanning strategies under different oral impression requirements. The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images, adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy. The scanning trajectories mainly include the E-shaped, segmented, and S-shaped methods. When performing fixed denture restoration, it is recommended to first scan the abutment and adjacent teeth. When performing fixed denture restoration, it is recommended to scan the abutment and adjacent teeth first. Then the cavity in the abutment area is excavated. Lastly, the cavity gap was scanned after completing the abutment preparation. This method not only meets clinical needs but also achieves the most reliable accuracy. When performing full denture restoration in edentulous jaws, setting markers on the mucosal tissue at the bottom of the alveolar ridge, simultaneously capturing images of the vestibular area, using different types of scanning paths such as Z-shaped, S-shaped, buccal-palatal and palatal-buccal pathways, segmented scanning of dental arches, and other strategies can reduce scanning errors and improve image stitching and overlap. For implant restoration, when a single crown restoration is supported by implants and a small span upper structure restoration, it is recommended to first pre-scan the required dental arch. Then the cavity in the abutment area is excavated. Lastly, scanning the cavity gap after installing the implant scanning rod. When repairing a bone level implant crown, an improved indirect scanning method can be used. The scanning process includes three steps: First, the temporary restoration, adjacent teeth, and gingival tissue in the mouth are scanned; second, the entire dental arch is scanned after installing a standard scanning rod on the implant; and third, the temporary restoration outside the mouth is scanned to obtain the three-dimensional shape of the gingival contour of the implant neck, thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration. For dental implant fixed bridge repair with missing teeth, the mobility of the mucosa increases the difficulty of scanning, making it difficult for scanners to distinguish scanning rods of the same shape and size, which can easily cause image stacking errors. Higher accuracy of digital implant impressions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius. The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases, the scanning accuracy decreases accordingly, especially when performing full mouth implant restoration impressions. The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal morphology inside the mouth and the lack of relatively obvious and fixed reference objects, which results in insufficient accuracy. When designing restorations of this type, it is advisable to carefully choose digital intraoral scanning methods to obtain model data. It is not recommended to use digital impressions when there are more than five missing teeth

ImDeeplabV3plus with instance selective whitening loss in domain generalization semantic segmentation

Abstract Semantic segmentation is a classical problem in computer vision, which is important in the field of autonomous driving. Although significant progress has been achieved in semantic segmentation, its generalization ability to unknown domains is still challenging. To effectively solve this problem, a semantic segmentation method ImDeeplabV3plus with instance selective whitening loss is proposed in this paper. DeeplabV3plus is selected as the baseline. In order to enhance the representation of the region of interest, the coordinate attention (CA) mechanism is added. To better integrate multiple low‐level features, the adaptively spatial feature fusion (ASFF) is employed to adaptively learn the importance of features at different levels for each location. For preferably coping with the domain changes, an instance selective whitening (ISW) loss is introduced in the early stage of the backbone. The model is trained with the Cityscapes dataset and then applied to the unknown domain RobotCar dataset. Compared with DeeplabV3plus, the authors’ ImDeeplabV3plus model shows 1.29% mIoU improvement. When ISW loss is added, 2.08% improvement in mIoU is achieved compared with ImDeeplabV3plus. Experimental results show that the proposed method is simple and improves the domain generalization ability

DataSheet_1_Integrative analysis identifies oxidative stress biomarkers in non-alcoholic fatty liver disease via machine learning and weighted gene co-expression network analysis.zip

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Given the absence of effective treatments to halt its progression, novel molecular approaches to the NAFLD diagnosis and treatment are of paramount importance.MethodsFirstly, we downloaded oxidative stress-related genes from the GeneCards database and retrieved NAFLD-related datasets from the GEO database. Using the Limma R package and WGCNA, we identified differentially expressed genes closely associated with NAFLD. In our study, we identified 31 intersection genes by analyzing the intersection among oxidative stress-related genes, NAFLD-related genes, and genes closely associated with NAFLD as identified through Weighted Gene Co-expression Network Analysis (WGCNA). In a study of 31 intersection genes between NAFLD and Oxidative Stress (OS), we identified three hub genes using three machine learning algorithms: Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine - Recursive Feature Elimination (SVM-RFE), and RandomForest. Subsequently, a nomogram was utilized to predict the incidence of NAFLD. The CIBERSORT algorithm was employed for immune infiltration analysis, single sample Gene Set Enrichment Analysis (ssGSEA) for functional enrichment analysis, and Protein-Protein Interaction (PPI) networks to explore the relationships between the three hub genes and other intersecting genes of NAFLD and OS. The distribution of these three hub genes across six cell clusters was determined using single-cell RNA sequencing. Finally, utilizing relevant data from the Attie Lab Diabetes Database, and liver tissues from NASH mouse model, Western Blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) assays were conducted, this further validated the significant roles of CDKN1B and TFAM in NAFLD.ResultsIn the course of this research, we identified 31 genes with a strong association with oxidative stress in NAFLD. Subsequent machine learning analysis and external validation pinpointed two genes: CDKN1B and TFAM, as demonstrating the closest correlation to oxidative stress in NAFLD.ConclusionThis investigation found two hub genes that hold potential as novel targets for the diagnosis and treatment of NAFLD, thereby offering innovative perspectives for its clinical management.</p

Effectiveness of inactivated COVID-19 vaccines against mild disease, pneumonia, and severe disease among persons infected with SARS-CoV-2 Omicron variant: real-world study in Jilin Province, China

ABSTRACTIt is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect