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Background Atherosclerosis (As) is a serious threat to human health. Although glucose balance, lipid metabolism, inflammation and hypertension have been found to be closely related to AS, it is crucially unclear, whether methyltransferase (METTL) family members are involved in the occurrence and development of AS.Methods The differentially expressed genes of METTLs in AS and normal blood vessels in GSE43292 and GSE100927 databases were analyzed. Random forest screening was used to screen marker genes, and the intersection genes in two databases were selected, while GSE28829/GSE41571 and clinical tissue samples were used for verification. The databases were further used to analyze the tissue and cell localization of marker genes and their correlation with lipid metabolism and immune cell infiltration.Results There were 7 and 17 differentially expressed METTL genes in GSE43292 and GSE100927 databases, respectively. 7 and 10 AS risk genes were selected by random forest screening. METTL7B and METTL5 were verified as the intersection marker genes using GSE28829, GSE41571 database and clinical AS samples. Compared with the control group, the expression of METTL7B in advanced AS, AS rupture plaque and clinical heavy load plaque tissue significantly increased, and the ROC curve analysis showed that the AUC of METTL7B in GSE28829 and GSE41571 was greater than 0.9. In addition, it was found that METTL7B was significantly correlated with lipid metabolism-related genes, and METTL7B could promote the formation of lipid droplets. METTL7B was positively correlated with immune cell infiltration and macrophage-mediated efferocytosis. Drugs such as FAD, Pralatrexate and Indinavir can act on METTL7B. This study reveals a new mechanism for the occurrence and development of AS thereby providing a potential target for the treatment of AS.Conclusion METTL7B can be used as a predictor and therapeutic target for AS.

Background Lung organoids have emerged as a promising tool for studying lung development, function, and disease pathology. The present study aimed to analyze the current status and development trends of lung organoid research over the past years, present visual representations, and provide references for future research directions using bibliometric analysis. Methods Information on articles on lung organoids extracted from the Web of Science Core Collection, such as year of publication, journal, country, institution, author, and keywords, was analyzed. R, VOSviewer, and SCImago Graphica were used to visualize publication trends, co-authorship analysis, co-occurrence analysis, and hotspot evolution. Results The number of global publications has increased from 1 in 2011 to 512 in 2022. The cell produced the highest number of citations (2,069 citations). The United States (6,694 citations and 177 publications), University Medical Center Utrecht (2,060 citations and 9 publications), and Clevers H (2,570 citations and 15 publications) were the most influential countries, institutions, and authors, respectively. Co-occurrence cluster analysis of the top 54 keywords formed four clusters: (1) pulmonary fibrosis (PF), (2) lung cancer, (3) cystic fibrosis (CF), (4) coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusion Organoid technology undoubtedly played an important role in the study of COVID-19, but with the passing of the COVID-19 epidemic, the research focus may return to refractory lung diseases such as PF, CF, and lung cancer. Standardized culture, living biobanks, and multimodal model systems for lung disease may be the future research directions in the field of lung organoids.

The breakup of non-Newtonian droplets is ubiquitous in numerous applications. Although the non-Newtonian property can significantly change the droplet breakup process, most previous studies consider Newtonian droplets, and the effects of the non-Newtonian properties on the breakup process are still unclear. This study focuses on the secondary breakup of shear-thinning droplets by numerical simulation. The volume of fluid method is used to capture interface dynamics on adaptive grids. To compare shear-thinning droplets and Newtonian droplets, a new definition of the Ohnesorge number is proposed by considering the characteristic shear rate in the droplet induced by the airflow. The results show that compared with the Newtonian fluid, the shear-thinning properties can change the effective viscosity distribution inside the droplet, alter the local deformation, change the droplet morphology, and affect the transition in the droplet breakup regime., 14 pages, 15 figures

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness. The migration rate of corneal epithelial cells directly affects corneal repair. Here, we explored ocu-microRNA 24-3p (miRNA 24-3p) that can promote rabbit corneal epithelial cells migration and cornea repair. Exosomes, an excellent transport carrier, were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes (Exos-miRNA 24-3p). It can accelerate corneal epithelial migration in vitro and in vivo. For application in cornea alkali burns, we further modified hyaluronic acid with di(ethylene glycol) monomethyl ether methacrylate (DEGMA) to obtain a thermosensitive hydrogel, also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel (THH) for the controlled release of Exos-miRNA 24-3p. It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug–ocular–epithelium contact time. The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation. It also reduced corneal stromal fibrosis and macrophage activation. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.

The Marangoni-driven film spreading in the fully miscible droplet–reservoir system was experimentally studied. Three stages of film spreading were identified over a relatively long time, with the power-law exponent n ( R ∼ tn, R is film radius, t is time) nonmonotonically transitioning from 3/4, to 1/4, and back to 3/4. The variation of the Marangoni stress was found to be responsible for the three-stage power-law relationships, with the tangential stretching effect of the expanding liquid–air interface governing stages I and III and the normal diffusion effect dominating stage II. This work presents a unified interpretation of the inconsistent power-law relationships reported from previous studies on Marangoni-driven film spreading for miscible fluids.

The impact of droplets on liquid pools is ubiquitous in nature and many industrial applications. Most previous studies of droplet impact focus on Newtonian fluids, while less attention has been paid to the impact dynamics of non-Newtonian droplets, even though non-Newtonian fluids are widely used in many applications. In this study, the splashing dynamics of shear-thinning droplets with yield stress are studied by combined experiments and simulations. The formation and the propagation of the ejecta sheet produced during the splashing process are considered, and the velocity, the radius, and the time of the ejecta sheet emergence are analyzed. The results show that the non-Newtonian fluid properties significantly affect the splashing process. The ejecta sheet of the splashing becomes easier to form as the flow index reduces, the large yield stress can affect the thickness of the ejecta sheet, and the spreading radius collapses into a geometrical radius due to that the inertia force is the dominant factor in the ejecta sheet propagation., 12 pages, 14 figures

Problem Osteoarthritis (OA) is a chronic disease with a very high incidence and the pathology of which is quite complex. Epidemiological investigation showed that OA may be related to smoking and estrogen levels, but there are few studies focused on the cross-effect of these two factors. This research aims to investigate the molecular mechanism of nicotine and estrogen effects on chondrocytes to study the effect of smoking on the incidence of osteoarthritis in women. Method of the study Nicotine was added to obtain inflammatory supernatants of macrophages, which were used to induce chondrocyte inflammation. Toluidine staining and immunohistochemistry were used to detect the extracellular matrix (ECM) of chondrocytes, while the important proteins in the metabolism of chondrocytes were detected by Western blot. Results Nicotine-induced inflammatory supernatant promoted the degradation of ECM, such as type II collagen, aggrecan and proteoglycan 4. While in the presence of physiological concentrations of estrogen, this destructive effect is reversed. On the molecular level, estrogen (17β-estradiol, 1 nmol/L) can inhibit the matrix degrading enzymes and promote the transforming growth factor (TGF)-β1 pathway which is involved in matrix synthesis. However, in the presence of inflammatory induction, although estrogen could still inhibit the expression of matrix degrading enzymes, it inhibited the TGF-β1 pathway. Moreover, the different inflammatory factors in the inflammatory supernatant, mainly tumor necrosis factor-α, interleukin-1β, had different effects on the metabolic processes of chondrocytes. Conclusion Estrogen reverses nicotine-induced inflammation mainly via reducing the degradation of ECM. The cross-effect of estrogen and inflammatory factor inhibitors can be a potential clinical reference for OA patients.

Background: The intracerebral hemorrhagic stroke (ICH) is associated with high mortality and severe disability in survivors, which causing about 42% of the disability-adjusted life years lost and 50% of all stroke patients dead within 1 year. Although early functional training is recommended to facility rehabilitation after the stroke, the benefit and safety are still controversial. Introduction: This systematic review aims to investigate whether early physical rehabilitation could have a beneficial effect for the patients with ICH compared with standard rehabilitation care. Methods and analysis: Pubmed, Embase, and Cochrane library will be searched to include randomized control trials which investigate the rehabilitation effective of the early mobilization for patients with ICH compared with routine nursing or standard care. Rev-Man version 5.3 will be used to perform all calculations related to the meta-analysis. Dichotomous data will be calculated in terms of a fixed or random effect model and expressed by the relative risk (RR) with 95% confidence interval (CI). The Cochrane collaborations tool in the following aspects was used to assess the risk of bias (ROB) in included studies. The inconsistency index (I2) and Chi-Squared will be applied for heterogeneity detection between clinical trials. A value of P

With the abuse of macrolide, lincosamide, and streptogramin (MLS), the traditionally safe bifidobacterial strains in the human intestine could serve as a reservoir of MLS resistance genes. In this study, the erm(X) gene was detected in 29 MLS-resistant strains and one MLS-susceptible strain among 92 bifidobacterial strains of human origin. This study is the first to report erm(X)-mediated MLS resistance in Bifidobacterium pseudocatenulatum, Bifidobacterium breve and Bifidobacterium bifidum. The insertion sequences (ISs) flanking antibiotic resistance (AR) genes (i.e., the genetic environment of AR genes) could contribute to the horizontal spreading of AR. However, the potential transferability of erm(X) in bifidobacteria has not been previously verified. Here, we retrieved four genetic environments (I-IV) of erm(X) from 30 erm(X)-positive bifidobacterial strains. This study is the first to identify the erm(X) gene in three new genetic environments (II, III and IV) in bifidobacteria. The erm(X) gene was individually flanked by IS1249 or IS3 in genetic environments I, II and IV and was simultaneously flanked by IS1249 and IS3 elements in genetic environment III. Only the transfer of erm(X) from genetic environment III simultaneously flanked by IS1249 and IS3 elements was successfully observed in filter mating experiments. These findings indicate a synergic effect of IS1249 and IS3 elements in the transfer of erm(X) in bifidobacteria, and further reveal that the various genetic environments of erm(X) result in significant differences in the transferability of erm(X) in bifidobacteria.

Background Heavy metal contamination is becoming a limitation to the utilization of soil and the distribution of vegetation. In particular, cadmium (Cd) pollution has had a serious impact on the food chain. Broussonetia papyrifera is a widely distributed pioneer tree species of heavy metal contaminated areas with important economic value. However, little is known about the genomic background of the Cd-tolerance mechanism in B. papyrifera. Results The CdCl2 responsive physiology was evaluated and proved to be involved in antioxidase activity and active oxygen species (ROS) accumulation. The leaf and root transcriptomes derived from B. papyrifera grown under normal and CdCl2 stress conditions were systematically investigated using the Illumina HiSeq method. A total of 180,678,660 bp (27.1 GB) clean reads were assembled into 589,487 high-quality unigenes, of which 256,025 (43.43% of the total) and 250,251 (42.45% of the total) were aligned in Gene Ontology (GO) and Protein family (Pfam), respectively. A total of 24,414 differentially expressed genes (DEGs) were GO-annotated into 53, 23, 55, and 60 terms from the transcriptomes of root and leaf tissues under Cd stress and control conditions. A total of 117,547 Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO)-annotated DEGs were enriched in at least 47 KEGG pathway terms among the four comparisons. Many genes encoding important transcription factors (e.g., auxin/indole-3-acetic acid (AUX/IAA), basic helix-loop-helix (bHLH), DNA-binding one zinc finger (Dof), and MYB) and proteins involved in plant-pathogen interactions, phenylpropanoid biosynthesis, plant hormone signal transduction, oxidative phosphorylation, carbon fixation, peroxisomes, flavonoid biosynthesis, and glutathione metabolism, among others, were substantially upregulated under CdCl2 stress. Conclusions These genes represent important candidates for studying Cd-response mechanisms and molecular biology of B. papyrifera and related species. Our findings provide a genomic sequence resource for functional genetic assignments in B. papyrifera, which will help elucidate the molecular mechanisms of its Cd-stress responses and facilitate the bioremediation of heavy metal contaminated areas via breeding of new stress-tolerant cultivars.

Lack of complete genomic information concerning Vicia sepium (Fabaceae: Fabeae) precludes investigations of evolution and populational diversity of this perennial high-protein forage plant suitable for cultivation in extreme conditions. Here, we present the complete and annotated chloroplast genome of this important wild resource plant. V. sepium chloroplast genome includes 76 protein-coding genes, 29 tRNA genes, 4 rRNA genes, and 1 pseudogene. Its 124,095 bp sequence has a loss of one inverted repeat (IR). The GC content of the whole genome, the protein-coding, intron, tRNA, rRNA, and intergenic spacer regions was 35.0%, 36.7%, 34.6%, 52.3%, 54.2%, and 29.2%, respectively. Comparative analyses with plastids from related genera belonging to Fabeae demonstrated that the greatest variation in the V. sepium genome length occurred in protein-coding regions. In these regions, some genes and introns were lost or gained; for example, ycf4, clpP intron, and rpl16 intron deletions and rpl20 and ORF292 insertions were observed. Twelve highly divergent regions, 66 simple sequence repeats (SSRs) and 27 repeat sequences were also found in these regions. Detailed evolutionary rate analysis of protein-coding genes showed that Vicia species exhibit additional interesting characteristics including positive selection of ccsA, clpP, rpl32, rpl33, rpoC1, rps15, rps2, rps4, and rps7, and the evolutionary rates of atpA, accD, and rps2 in Vicia are significantly accelerated. These genes are important candidate genes for understanding the evolutionary strategies of Vicia and other genera in Fabeae. The phylogenetic analysis showed that Vicia and Lens are included in the same clade and that Vicia is paraphyletic. These results provide evidence regarding the evolutionary history of the chloroplast genome.

Human cytomegalovirus (HCMV) has been reported to be highly expressed in essential hypertension (EH), and it has been proposed that HCMV infection may contribute to EH development. However, different studies showed opposite results. The present meta-analysis was performed to investigate the association between HCMV infection and the risk of EH. All relevant literature from 1980 to 2015 was extracted from six electronic databases. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of the association of HCMV infection and risk of EH. Sensitivity analysis and examination for bias were conducted to evaluate cumulative evidence of the association. The random-effect model using the Mantel-Haenszel method was used to give the individual effect-size estimates. Of the 11,878 participants included in this study, there were 3,864 EH patients and 8,014 control subjects. Meta-analysis of nine studies performed in a random-effect model found that EH patients had a higher risk of HCMV infection than normal control subjects (OR = 1.47, 95%CI: 1.13-1.90, P = 0.004; heterogeneity: I(2) = 66%, P = 0.002). Sensitivity analysis and bias examination showed the overall quality and consistency of the studies to be acceptable. For subgroup analysis, studies of Chinese populations were selected for further analysis. There was a significant association between HCMV infection and EH among Chinese patients (OR = 2.18, 95%CI:1.43-3.31, P = 0.0003) but not among other ethnic groups (OR = 1.11, 95%CI:0.95-1.31, P = 0.19). These findings provide quantitative support for the association between HCMV infection and high risk of EH in individuals of Chinese ethnicity.

Liquid chromatography tandem mass spectrometry (LC–MS/MS), especially triple-quadrupole mass spectrometry, has become an attractive alternative method to ligand binding assays for therapeutic monoclonal antibody quantification in biological samples, but the use of an internal standard with infliximab LC–MS/MS assays has not been reported yet. In this study, an improved LC–MS/MS method for quantification of infliximab in human serum was developed and validated. A surrogate peptide was used as a representative of infliximab which was cleaved for the quantification of infliximab based on LC–MS/MS assay. A stable isotope-labeled signature peptide was used as the internal standard (IS). The results showed linearity in the range of 0.39–100 μg mL−1; the lower limit of quantification (LLOQ), and the lower limit of detection were 0.39 and 0.0975 μg mL−1, respectively. The quality control (QC) data showed that the within-run, between-run precision (%RSD) and accuracy (%RE) conformed to the acceptance criteria of ±15 % for calibration standards and QCs (±20 % at the LLOQ). Other validation parameters including selectivity, methanol precipitation efficiency, serum matrix effect, stability, and auto-sampler carry-over were also evaluated. This improved LC–MS/MS method might be a promising LC–MS-based methodology for pharmacokinetic studies of other recombinant monoclonal antibodies.

Human cytomegalovirus (HCMV) has been reported to be highly expressed in essential hypertension (EH), and it has been proposed that HCMV infection may contribute to EH development. However, different studies showed opposite results. The present meta-analysis was performed to investigate the association between HCMV infection and the risk of EH. All relevant literature from 1980 to 2015 was extracted from six electronic databases. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of the association of HCMV infection and risk of EH. Sensitivity analysis and examination for bias were conducted to evaluate cumulative evidence of the association. The random-effect model using the Mantel-Haenszel method was used to give the individual effect-size estimates. Of the 11,878 participants included in this study, there were 3,864 EH patients and 8,014 control subjects. Meta-analysis of nine studies performed in a random-effect model found that EH patients had a higher risk of HCMV infection than normal control subjects (OR = 1.47, 95%CI: 1.13-1.90, P = 0.004; heterogeneity: I(2) = 66%, P = 0.002). Sensitivity analysis and bias examination showed the overall quality and consistency of the studies to be acceptable. For subgroup analysis, studies of Chinese populations were selected for further analysis. There was a significant association between HCMV infection and EH among Chinese patients (OR = 2.18, 95%CI:1.43-3.31, P = 0.0003) but not among other ethnic groups (OR = 1.11, 95%CI:0.95-1.31, P = 0.19). These findings provide quantitative support for the association between HCMV infection and high risk of EH in individuals of Chinese ethnicity.

Panitumumab, as a commercially available antibody, is an effective anticancer therapeutic against epidermal growth factor receptor (EGFR), although it exerts weak antibody-dependent cell-mediated cytotoxicity (ADCC) activity owing to its IgG2 nature. Here, we firstly engineered panitumumab by grafting its variable region into an IgG1 backbone. The engineered panitumumab (denoted as Pan) retained binding activity identical to the parental antibody while exhibiting stronger ADCC activity in vitro and more potent antitumor effect in vivo. To further enhance the target selectivity of Pan, we generated Pan-P by tethering an epitope-blocking peptide to Pan via a tumor-specific protease selective linker. Pan-P showed almost 40-fold weaker affinity compared with Pan, but functional activity was restored to a similar extent as Pan when Pan-P was selectively activated by urokinase-type plasminogen activator (uPA). More importantly, targeted localization of Pan-P was observed in tumor samples from colorectal cancer (CRC) patients and tumor-bearing nude mice, strongly indicating that specific activation also existed ex vivo and in vivo. Furthermore, Pan-P also exhibited effective in vivo antitumor potency similar to Pan. Taken together, our data evidence the enhanced antitumor potency and excellent target selectivity of Pan-P, suggesting its potential use for minimizing on-target toxicity in anti-EGFR therapy.

Essential hypertension (EH) is regarded as a multifactorial and poly- genic disease, and its underlying mecha- nism is very complex. A new model of EH pathogenesis was developed in the pres- ent work. This model is suitable for the study, diagnosis, treatment, and preven- tion of EH. It incorporates not only genetic and environmental factors, but also com- pensatory and time factors as the third and fourth types of factors that contribute to the development of EH. Compensatory factors are defined here as specific blood pressure (BP) regulators, the ability of the body to regulate BP, and the process of BP regulation. Time factors include the age of the patient and the duration of EH in that patient. Over time, genetic, environmental, compensatory, and time factors are dy- namic. In this way, the development of EH is influenced by the interactions between these four factors. Herein, a 4-dimension- al (4-D) model of EH pathogenesis is de- scribed, including primary approaches and technical considerations. The 4-D model will be useful in understanding the pathogenesis, diagnosis, treatment, and prevention of EH.

More and more debris flows were caused by human activities. Firstly its definition of human debris flows was set up, the correlation between the two objects was analyzed. It think that human activities destroy the ecological environment so that had effect on the Forming condition and the development of the human debris flows through the following three ways: changing the natural terrain, providing loose solid materials and hydrodynamic. In the end some prevention measures were put forward on the basis of the control status of the debris flows.