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Abstract Aim of the study We aimed to elucidate the synergistic effect and potential mechanism of New Baitouweng Decoction (NBD) combined with fecal microbiota transplantation (FMT) in rats with DSS-induced ulcerative colitis (UC). Materials and methods Colitis was induced by 5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. NBD or NBD combined with FMT were administered to the colitis rats. Body weight and disease activity index were measured, and the colon histological change was imaged to further examine the efficacy of NBD and FMT. The specific effects of NBD on STAT3/NF-κB signaling pathway and gut microbiota in rats with UC were also investigated. Results The efficacy of NBD in combination with FMT was demonstrated by the lower disease activity index scores; increased tight junction proteins expression; and a lower expression of macrophage marker (F4/80) in colon tissues. NBD combined with FMT elevated the concentrations of short-chain fatty acids and inhibited activation of the JAK2/STAT3/NF-κB related proteins. Furthermore, 16SrDNA sequencing indicated that the gut microbiota in rats with UC was perturbed, in contrast to that in healthy rats. After treatment with NBD and FMT, the diversity and abundance of intestinal flora showed clear improvements. Spearman correlation analysis indicated a strong correlation between specific microbiota and fecal concentrations of acetate, propionate and butyrate. Conclusions The protective mechanism of NBD combined with FMT may be linked to regulation NF-κB/STAT3 and restoration of the intestinal flora.

Due to the possibility of causing eutrophication, excessive phosphate discharged into water bodies always threatens the stabilization of aquatic ecosystem. A promising strategy is to remove phosphate from water by the utilization of biomass waste as adsorbents. In this paper, the corn straw (CS) and pine sawdust (PS) are chosen for adsorption; however, the phosphate removal capacities of them are very limited. Considering the high phosphate uptake of trivalent cerium, Ce (III)-based nanoparticles (CD and CT) are selected to be loaded on the biomass by hydrothermal synthesis to obtain four modified materials. CD is metal organic frameworks (MOFs) with Ce5(BDC)7.5(DMF)4 as its molecular structure, while CT is MOFs derivatives with [Ce (HCOO)]n as its crystal structure. The adsorption capacities of CS-CD, PS-CD, CS-CT and PS-CT reach 181.38, 183.27, 225.55 and 186.23 mg/g. But on account of the different molecular structures, CS-CD and PS-CD achieve great phosphate uptake under wide applicable scope of pH from 2 to 11, whereas CS-CT and PS-CT only under acidic conditions. The analysis of the adsorption mechanism indicates that due to the unsaturated coordination bond of CD, it could remove phosphate through coprecipitation and ion exchange even under alkaline conditions. HIGHLIGHTS The modified biomass wastes by cerium-based nanoparticles were developed to enhance their phosphate removal.; The CD and CT are all dominated by trivalent cerium.; Different from CD, CT is a MOF derivative, with cerium atom nine fold coordinated.; CS-CT showed high adsorption capacity of 225.55 mg/g.; CS-CD and PS-CD exhibited higher phosphate capacities in a wide pH range due to their unsaturated coordination.;

Abstract Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening lung diseases associated with acute and severe inflammation. Both have high mortality rates, and despite decades of research on clinical ALI/ARDS, there are no effective therapeutic strategies. Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury. Recently, studies on the role of extracellular vesicles (EVs) in regulating normal and pathophysiologic cell activities, including inflammation and injury responses, have attracted attention. Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes, which can be used to diagnose and predict the development of ALI/ARDS. EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function, and thereby promote cell proliferation and tissue regeneration. This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation, particularly ALI/ARDS.

Abstract Evidence suggests that probiotic interventions reduce non-communicable diseases (NCDs) risk. However, its therapeutic effect and mechanism are still unclear. To evaluate the hypocholesterolemic effect of Lactobacillus plantarum H6 (L.p H6), a new commercial patent strain capable of preventing hypercholesterolemia, and its mechanism in depth, three states of the strain were prepared, namely, viable (vH6), heat-inactivated (iH6), and ultrasonically-lysed (uH6) bacteria cells. The results showed that v/i/uH6 cells could lower serum and liver blood lipid levels, alleviate liver damage and improve glucose tolerance test (GTT) and insulin tolerance test (ITT) indexes. v/i/uH6 cells improved the gut microbial composition and significantly reduced the Firmicutes to Bacteroidetes ratio (F/B ratio) in feces. In particular, Muribaculaceae may be a potential biomarker for effective cholesterol reduction. Also, the recovery of these biochemical indices and gut microbiome was found following fecal microbiota transplantation (FMT) using stool from vH6 treated mice. The v/i/uH6 cells increased the intestinal flora metabolism of vitamins-cofactors, as well as amino acids, while decreasing the relative content of primary bile acids. The Pearson correlation analysis showed that norank_f__Muribaculaceae and Lactobacillus had a negative correlation with blood lipid levels. Overall, v/i/uH6 cells were effective in improving hypercholesterolemia in mice, and this effect was attributed partly to the regulation of intestinal microbiota and metabolites related to lipid metabolism. Our findings provided a theoretical basis for the industrial development of probiotics and postbiotics and the treatment of cholesterol diseases.

Objective To optimize the existing spin-EB method and promote human induced pluripotent stem cells (hiPSCs) differentiate into megakaryocytes (MKs). Methods In this study, the initial inoculation amount of hiPSCs was increased from 3 500 cells/well to 8 000 cells/well, and the size of EB was increased. By observing the generation time of EB- hematopoietic cells during differentiation, and detecting the proliferation of CD34+ hematopoietic progenitor cells and CD41+ MKs in different stages, it was studied whether the optimized scheme could promote the differentiation of hiPSCs into hematopoietic progenitor cells(HPCs) and MKs. Results By increasing the initial inoculation amount of hiPSCs and the size of EB, the differentiation of hiPSCs into HPCs and MKs and the cell production efficiency can be promoted. Conclusion Our research describes an optimized and repeatable differentiation method, which can produce hematopoietic progenitor cells and mature MKs from hiPSCs in a relatively short time with higher yield. It is of great clinical significance and broad scientific research prospect to continuously optimize the culture scheme of hiPSCs differentiation to produce MKs and platelets in vitro, and to promote large-scale platelet generation in vitro in transfusion medicine.

Abstract Many psychrophilic microorganisms synthesize ice-binding proteins (IBPs) to survive the cold. The functions of IBPs are evaluated by the effect of the proteins on the nonequilibrium water freezing-point depression, which is called “thermal hysteresis (TH)”, and the inhibitory effect of the proteins on the growth of larger ice crystals, which is called “ice recrystallization inhibition (IRI)”. To obtain mechanical insight into the two activities, we developed a modified method of ice affinity purification and extracted two new IBP isoforms from Psychromyces glacialis, an Arctic glacier fungus. One isoform was found to be an approximately 25 kDa protein (PsgIBP_S), while the other is a 28 kDa larger protein (PsgIBP_L) that forms an intermolecular dimer. Their TH activities were less than 1 °C at millimolar concentrations, implying that both isoforms are moderately active but not hyperactive IBP species. It further appeared that both isoforms exhibit high IRI activity even at submicromolar concentrations. Furthermore, the isoforms can bind to the whole surface of a hemispherical single ice crystal, although such ice-binding was generally observed for hyperactive IBP species. These results suggest that the binding ability of IBPs to whole ice crystal surfaces is deficient for hyperactivity but is crucial for significant IRI activity.

Chronic inflammation is frequently observed in patients with myeloproliferative neoplasms (MPN). Here the authors observe elevated levels of IL-1α and IL-1β in MPN patients and show that IL-1 contributes to clonal expansion and bone marrow fibrosis in a mouse model of MPN, proposing targeting of IL1R1 as therapeutic intervention.

Abstract We assessed the use of common urodynamics (CUD) combined with contrast‐enhanced ultrasound (CEUS) to investigate the efficacy and durability of sigmoid cystoplasty alone in patients with low bladder compliance associated with vesicoureteric reflux (VUR). In this study, we recruited 25 patients with low bladder compliance and VUR who underwent bladder augmentation without antireflux surgery at our institutions between June 2017 and June 2021. The bladder condition and VUR grade were assessed preoperatively and postoperatively via CUD combined with CEUS. The mean follow‐up period was 2.6 years. CUD showed significant improvement in bladder capacity and compliance and a decrease in intravesical pressure after sigmoid cystoplasty. CEUS demonstrated resolution of VUR compared with preoperative assessment. Of the 25 patients who had various degrees of reflux, VUR was eliminated in 18 patients and reduced to a lower grade in the remaining seven patients. CUD combined with CEUS is accurate and safe. They are invaluable and reliable tools for morphological and functional evaluations of the entire urinary tract in patients with low bladder compliance and VUR.

Triglyceride and glucose levels are important indicators for determining metabolic syndrome, one of the leading public-health burdens worldwide. Drosophila melanogaster is an ideal model for investigating metabolic diseases because it has 70% homology to human genes and its regulatory mechanism of energy metabolism homeostasis is highly similar to that of mammals. However, traditional analytical methods of triglyceride and glucose are time-consuming, laborious, and costly. In this study, a simple, practical, and reliable near-infrared (NIR) spectroscopic analysis method was developed for the rapid determination of glucose and triglyceride levels in an in vivo model of metabolic disorders using Drosophila induced by high-sugar or high-fat diets. The partial least squares (PLS) model was constructed and optimized using different spectral regions and spectral pretreatment methods. The overall results had satisfactory prediction performance. For Drosophila induced by high-sugar diets, the correlation coefficient (RP) and root mean square error of prediction (RMSEP) were 0.919 and 0.228 mmoL gprot−1 for triglyceride and 0.913 and 0.143 mmoL gprot−1 for glucose respectively; for Drosophila induced by high-fat diets, the RP and RMSEP were 0.871 and 0.097 mmoL gprot−1 for triglyceride and 0.853 and 0.154 mmoL gprot−1 for glucose, respectively. This study demonstrated the potential of using NIR spectroscopy combined with PLS in the determination of triglyceride and glucose levels in Drosophila, providing a rapid and effective method for monitoring metabolite levels during disease development and a possibility for evaluating metabolic diseases in humans in clinical practice.

Seed coat color is a typical morphological trait that can be used to reveal the evolution of soybean. The study of seed coat color-related traits in soybeans is of great significance for both evolutionary theory and breeding practices. In this study, 180 F10 recombinant inbred lines (RILs) derived from the cross between the yellow-seed coat cultivar Jidou12 (ZDD23040, JD12) and the wild black-seed coat accession Y9 (ZYD02739) were used as materials. Three methods, single-marker analysis (SMA), interval mapping (IM), and inclusive composite interval mapping (ICIM), were used to identify quantitative trait loci (QTLs) controlling seed coat color and seed hilum color. Simultaneously, two genome-wide association study (GWAS) models, the generalized linear model (GLM) and mixed linear model (MLM), were used to jointly identify seed coat color and seed hilum color QTLs in 250 natural populations. By integrating the results from QTL mapping and GWAS analysis, we identified two stable QTLs (qSCC02 and qSCC08) associated with seed coat color and one stable QTL (qSHC08) related to seed hilum color. By combining the results of linkage analysis and association analysis, two stable QTLs (qSCC02, qSCC08) for seed coat color and one stable QTL (qSHC08) for seed hilum color were identified. Upon further investigation using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we validated the previous findings that two candidate genes (CHS3C and CHS4A) reside within the qSCC08 region and identified a new QTL, qSCC02. There were a total of 28 candidate genes in the interval, among which Glyma.02G024600, Glyma.02G024700, and Glyma.02G024800 were mapped to the glutathione metabolic pathway, which is related to the transport or accumulation of anthocyanin. We considered the three genes as potential candidate genes for soybean seed coat-related traits. The QTLs and candidate genes detected in this study provide a foundation for further understanding the genetic mechanisms underlying soybean seed coat color and seed hilum color and are of significant value in marker-assisted breeding.

Aim: We performed a systematic review and network meta-analysis evaluating the safety and efficacy of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among dialysis chronic kidney disease patients.Methods: Safety was evaluated with any adverse events (AEs), serious adverse events (SAEs), and 12 common events. Efficacy was mainly analyzed with hemoglobin response. All reported results were summarized using mean difference and risk ratio (RR) with 95% confidence interval (CI). Publication bias was assessed through funnel plots.Results: Twenty trials (19 studies) with 14,947 participants were included, comparing six HIF-PHIs with erythropoiesis-stimulating agents (ESAs). No significant differences were indicated in overall AEs and SAEs between each HIF-PHI and ESA. The occurrence of gastrointestinal disorder was higher in enarodustat and roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52–31.40, p = 0.01; RR: 1.30, 95% CI: 1.04–1.61, p = 0.02). The occurrence of hypertension was lower in vadadustat than in ESAs (RR: 0.81, 95% CI: 0.69–0.96, p = 0.01). The occurrence of vascular-access complications was higher in roxadustat (RR: 1.15, 95% CI: 1.04–1.27, p

IntroductionAcute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD.MethodsTranscriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines.ResultsWe identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A, and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling.DiscussionOur findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.

ObjectiveThis study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers.MethodsA total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified.ResultsBased on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (P

Osteoarthritis (OA) is a chronic progressive degenerative joint disease. Owing to its complex pathogenesis, OA treatment is typically challenging. Necroptosis is a form of programmed cell death mainly mediated by the serine/threonine kinases, RIPK1 and RIPK3, and mixed lineage kinase-like domain (MLKL). In this study, we found that the multi-targeted kinase inhibitor DCC-2036 can inhibit TSZ (TNF-α, Smac mimetic, and z-VAD-FMK)-induced necroptosis of chondrocytes and synovial fibroblast cells (SFs). In addition, we found that oral DCC-2036 inhibited chondrocyte damage in a rat model of OA induced by intra-articular injection of monosodium iodoacetate (MIA). A mechanistic study showed that DCC-2036 directly inhibited the activities of RIPK1 and RIPK3 kinases to block necroptosis, inhibiting the inflammatory response and protecting chondrocytes. In summary, our research suggests that DCC-2036, a new necroptosis inhibitor targeting RIPK1 and RIPK3 kinase activity, may be useful for the clinical treatment of OA and provides a new direction for the research and treatment of OA.

Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the “4D-sEVs”). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.

Objective: The aim of this study is to acquire pulmonary CT (Computed tomography) angiographic data for the purpose of creating a three-dimensional reconstruction. Additionally, we aim to analyze the features and deviations of the branches in both pulmonary lobes. This information is intended to serve as a more comprehensive and detailed reference for medical professionals when conducting preoperative evaluations and devising surgical plans.Method: Between August 2019 and December 2021, 420 patients were selected from the thoracic surgery department at the First Hospital of Jilin University, and underwent pulmonary 64 channel contrast enhanced CT examinations (Philips ICT 256). The images were acquired at a 1.5 mm slice thickness, and the DCM files that complied with DICOM (Digital Imaging and Communications in Medicine) standards were analysed for 3D (three dimensional) reconstruction using Mimics 22.0 software. The reconstructed pulmonary artery models were assessed by attending chest surgeons and radiologists with over 10 years of clinical experience. The two-dimensional image planes, as well as the coronary and sagittal planes, were utilized to evaluate the arteries. The study analyzed the characteristics and variations of the branches and courses of pulmonary arteries in each lobe of the lungs, with the exception of the subsegmental arterial system. Two chest surgeons and two radiologists with professional titles-all of whom had over a decade of clinical experience-jointly evaluated the 3D models of the pulmonary artery and similarly assessed the characteristics and variations of the branches and courses in each lobe of the lungs.Results: Significant variations were observed in the left superior pulmonary artery across the 420 subjects studied. In the left upper lobe, the blood supply of 4 arteries accounted for 50.5% (n = 212), while the blood supply of 2 arteries in the left lower lobe was the most common, accounting for 79.5% (n = 334). The greatest variation in the right pulmonary artery was observed in the branch supply of the right upper lobe mediastinal artery. In the majority of cases (77.9%), there were two arteries present, which was the most common configuration observed accounting for 64% (n = 269). In the right inferior lobe of the lung, there were typically 2–4 arteries, with 2 arteries being the most common configuration (observed in 79% of cases, n = 332).Conclusion: The three-dimensional reconstruction of pulmonary artery CT angiography enables clear observation of the branches and distribution of the pulmonary artery while also highlighting any variations. This technique holds significant clinical value for preoperative assessments regarding lesions and blood vessels.

Transportation of livestock is unavoidable in animal production. A total of 72 piglets were randomly divided into the CON group and the TSG group, and the piglets in CON group were transported for two hours. The purpose of this study was to determine the effects of short-distance road transportation lasting 2 h on the jejunum of weaned piglets. Our results showed that compared with the control group, there was no impact on the growth performance of piglets in the transport group (P > 0.05). The concentrations of cortisol, heat shock protein (HSP)70, HSP90, C-reactive protein, interleukin (IL)-6, IL-8, IL-12, and interferon-γ and the activity of reactive oxygen species were increased in the jejunum of piglets in the transport group (P < 0.05 compared with the control group). The concentrations of glutathione peroxidase, claudin-1, occludin, and zonula occludens-1 showed no between-group differences (P > 0.05). Regarding intestinal morphology, the transport group showed infiltration of a small amount of lymphocytes into the jejunum mucosa epithelium that was accompanied by edema of the lamina propria, whereas the control group showed no obvious abnormalities. At the genus level, in the transport group, the 16S rRNA sequencing revealed a downward trend in the relative abundance of Lactobacillus and an upward trend in the relative abundance of Muribaculaceae_unclassified. There was also increased mRNA expression of genes associated with inflammation in the transport group, but the genes and pathways related to apoptosis were not activated. In summary, weaned piglets undergoing 2 h of short-distance road transportation showed stress and inflammatory reactions of the jejunum but did not exhibit oxidative damage or activation of the apoptosis pathway of the jejunum. Furthermore, the growth performance of the piglets was not affected by the trip.

Vessel segmentation in optical coherence tomography angiography (OCTA) is crucial for the detection and diagnosis of various eye diseases. However, it is hard to distinguish intricate vessel morphology and quantify the density of blood vessels due to the large variety of vessel sizes, significant background noise, and small datasets. To this end, a retinal angiography multi-scale segmentation network, integrated with the inception and squeeze-and-excitation modules, is proposed to address the above challenges under the one-shot learning paradigm. Specifically, the inception module extends the receptive field and extracts multi-scale features effectively to handle diverse vessel sizes. Meanwhile, the squeeze-and-excitation module modifies channel weights adaptively to improve the vessel feature extraction ability in complex noise backgrounds. Furthermore, the one-shot learning paradigm is adapted to alleviate the problem of the limited number of images in existing retinal OCTA vascular datasets. Compared with the classic U2-Net, the proposed model gains improvements in the Dice coefficient, accuracy, precision, recall, and intersection over union by 3.74%, 4.72%, 8.62%, 4.87%, and 4.32% respectively. The experimental results demonstrate that the proposed one-shot learning method is an effective solution for retinal angiography image segmentation.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from−0.505 to −0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.

Quantitatively revealing the response of carbon stocks to land use change (LUCC) and analyzing the vulnerability of ecosystem carbon stock (ECS) services are of great significance for maintaining the carbon cycle and ecological security. For this study, China’s Guizhou Province was the study area. Land use data in 2000, 2010, and 2020 were selected to explore the impacts of LUCC on carbon stocks in multiple scenarios by combining the PLUS and InVEST models and then analyzing the vulnerability of ECS services. The results show that forest land plays an important role in improving ECS services in karst plateau mountainous areas. In 2000–2020, forest land expansion offset the carbon stock reduced by the expansion of built-up land, greatly improving the regional ECS function. Following the natural trend (NT), the total carbon stock in Guizhou Province will decrease by 1.86 Tg; however, under ecological protection (EP) measures, the ECS service performs a positive function for LUCC. Focusing on socioeconomic development (ED) will increase the vulnerability of the regional ECS service. In the future, the forest land area size should be increased, and built-up land should be restricted to better improve the service function of ECS in karst plateau mountainous areas.

Central Asia is one of the most sensitive regions to climate changes in the world and the grassland degradation of this region has attracted considerable concern. Quantifying the driving force of grassland degradation is important for understanding the effects of climate variation and human activities on grassland. In this study, net primary productivity (NPP) was selected as an indicator to quantitatively evaluate the relative role of climate variation and human activities in Central Asia from 2000 to 2020. This study used the global NPP product MOD17A3 as actual NPP and estimated the potential NPP using the Thornthwaite memorial model. The potential NPP and the difference between the potential NPP and actual NPP were used to represent the influence of climate variation and human activities. The grassland degradation or restoration can be demonstrated by the slope of actual NPP (SA). A positive slope value (SA) suggested that restoration occurs, whereas a negative slope value suggested that degradation occurred. The results showed that 23.08% of the total grassland area experienced grassland degradation, whereas 2.51% of the whole grassland underwent grassland restoration. Furthermore, 53.8% of the degraded grassland areas were influenced by climate variation, and 14.5% were caused by human activities. By contrast, the relative roles of climate variation and human activities in grassland restoration were 25% and 47.9%, respectively. The NPP variation also could be calculated by assessing the effects of these factors and the results showed that 55.7% of the NPP decrease was caused by climate variation, whereas 9.6% was a result of human activities. On the contrary, climate variation and human activities resulted in 19.8% and 37.3% of grassland restoration, respectively. Therefore, climate variation was the dominant factor of grassland degradation, and human activities were the main driver of grassland restoration in Central Asia.

Pineapple color yellowing and quality promotion gradually manifest as pineapple fruit ripening progresses. To understand the molecular mechanism underlying yellowing in pineapples during ripening, coupled with alterations in fruit quality, comprehensive metabolome and transcriptome investigations were carried out. These investigations were conducted using pulp samples collected at three distinct stages of maturity: young fruit (YF), mature fruit (MF), and fully mature fruit (FMF). This study revealed a noteworthy increase in the levels of total phenols and flavones, coupled with a concurrent decline in lignin and total acid contents as the fruit transitioned from YF to FMF. Furthermore, the analysis yielded 167 differentially accumulated metabolites (DAMs) and 2194 differentially expressed genes (DEGs). Integration analysis based on DAMs and DEGs revealed that the biosynthesis of plant secondary metabolites, particularly the flavonol, flavonoid, and phenypropanoid pathways, plays a pivotal role in fruit yellowing. Additionally, RNA-seq analysis showed that structural genes, such as FLS, FNS, F3H, DFR, ANR, and GST, in the flavonoid biosynthetic pathway were upregulated, whereas the COMT, CCR, and CAD genes involved in lignin metabolism were downregulated as fruit ripening progressed. APX as well as PPO, and ACO genes related to the organic acid accumulations were upregulated and downregulated, respectively. Importantly, a comprehensive regulatory network encompassing genes that contribute to the metabolism of flavones, flavonols, lignin, and organic acids was proposed. This network sheds light on the intricate processes that underlie fruit yellowing and quality alterations. These findings enhance our understanding of the regulatory pathways governing pineapple ripening and offer valuable scientific insight into the molecular breeding of pineapples.

The effect of heat treatment on the microstructure and tensile properties of an as-cast Al0.6CoCrFeNi high-entropy alloy (HEA) was investigated in this paper. The results show that the as-cast Al0.6CoCrFeNi HEA presents a typical FCC dendrite morphology with the interdendritic region consisting of BCC/B2 structure and heat treatment can strongly affect the microstructure and mechanical properties of HEA. Microstructure analysis revealed the precipitation of a nano-sized L12 phase in the FCC dendrite and the formation of the FCC and σ phases in the interdendritic region after annealing at 700 °C. The coarse B2 phase was directly precipitated from the FCC dendrite in the 900 °C-annealed sample, with the coexistence of the B2, FCC, and σ phases in the interdendritic region. Then, the interdendritic region converted to a B2 and FCC dual-phase structure caused by the re-decomposition of the σ phase after annealing at 1100 °C. The tensile test results show that the 700 °C-annealed HEA presents the most significant strengthening effect, with increments of corresponding yield strength being about 107%, which can be attributed to the numerous nano-sized L12 precipitates in the FCC dendrite. The mechanical properties of 1100 °C-annealed alloy revert to a level close to that of the as-cast alloy, which can be attributed to the coarsening mechanism of B2 precipitates and the formation of a soft FCC phase in the interdendritic region. The observed variation in mechanical properties during heat treatment follows the traditional trade-off relationship between strength and plasticity.

Influenza vaccines faced significant challenges in achieving sufficient protective efficacy and production efficiency in the past. In recent decades, novel influenza vaccines, characterized by efficient and scalable production, advanced platforms, and new adjuvant technologies, have overcome some of these weaknesses and have been widely licensed. Furthermore, researchers are actively pursuing the development of next-generation and universal influenza vaccines to provide comprehensive protection against potential pandemic subtypes or strains. However, new challenges have emerged as these novel vaccines undergo evaluation and authorization. In this review, we primarily outline the critical challenges and advancements in research and development (R&D) and highlight the improvements in regulatory responses for influenza vaccines.

Compared with conventional cylinder airlift bioreactors (CCABs) that produce coarse bubbles, a novel rectangular dynamic membrane airlift bioreactor (RDMAB) developed in our lab produces fine bubbles to enhance the volumetric oxygen mass transfer coefficient (kLa) and gas holdup, as well as improve the bioprocess in a bioreactor. In this study, we compared mass transfer, gas holdup, and batch and continuous fermentation for RNA production in CCAB and RDMAB. In addition, unstructured kinetic models for microbial growth, substrate utilization, and RNA formation were established. In batch fermentation, biomass, RNA yield, and substrate utilization in the RDMAB were higher than those in the CCAB, which indicates that dynamic membrane aeration produced a high kLa by fine bubbles; a higher kLa is more beneficial to aerobic fermentation. The starting time of continuous fermentation in the RDMAB was 20 h earlier than that in the CCAB, which greatly improved the biological process. During continuous fermentation, maintaining the same dissolved oxygen level and a constant dilution rate, the biomass accumulation and RNA concentration in the RDMAB were 9.71% and 11.15% higher than those in the CCAB, respectively. Finally, the dilution rate of RDMAB was 16.7% higher than that of CCAB during continuous fermentation while maintaining the same air aeration. In summary, RDMAB is more suitable for continuous fermentation processes. Developing new aeration and structural geometry in airlift bioreactors to enhance kLa and gas holdup is becoming increasingly important to improve bioprocesses in a bioreactor.

Abstract Background We examined attitudes toward the COVID‐19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods A multicenter, web‐based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results Of the unvaccinated patients, 32.9% were willing to receive the COVID‐19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine‐related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID‐19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow‐up of 88 (38, 131) days, patients' disease activities were stable. Conclusions The findings show that AIIRD patients were unwilling to receive the COVID‐19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID‐19 disease and vaccines had a significant effect on vaccination willingness.

Abstract Electrochemical CO2 reduction reaction (CO2RR) to multi-carbon products would simultaneously reduce CO2 emission and produce high-value chemicals. Herein, we report Cu electrodes modified by metal–organic framework (MOF) exhibiting enhanced electrocatalytic performance to convert CO2 into ethylene and ethanol. The Zr-based MOF, UiO-66 would in situ transform into amorphous ZrOx nanoparticles (a-ZrOx), constructing a-ZrOx/Cu hetero-interface as a dual-site catalyst. The Faradaic efficiency of multi-carbon (C2+) products for optimal UiO-66-coated Cu (0.5-UiO/Cu) electrode reaches a high value of 74% at − 1.05 V versus RHE. The intrinsic activity for C2+ products on 0.5-UiO/Cu electrode is about two times higher than that of Cu foil. In situ surface-enhanced Raman spectra demonstrate that UiO-66-derived a-ZrOx coating can promote the stabilization of atop-bound CO* intermediates on Cu surface during CO2 electrolysis, leading to increased CO* coverage and facilitating the C–C coupling process. The present study gives new insights into tailoring the adsorption configurations of CO2RR intermediate by designing dual-site electrocatalysts with hetero-interfaces.

Ultrasound cycloplasty(UCP)procedure using high intensity focused ultrasound(HIFU)is a new non-invasive glaucoma treatment based on miniaturized transducers. In recent years, the safety and efficacy of UCP on various types of glaucoma have been well verified, and it has shown broad application prospects in the treatment of glaucoma. This article collects and reviews the relevant literature on glaucoma treatment by UCP, and summarizes the information on the development of equipment, composition and operation, treatment mechanisms, indications, efficacy and safety, with the purpose to provide relevant basis for clinical applications and future research.

Soil displacement caused by frost heave and thawing settlement will pose a great threat to the structural safety of buried pipelines. Herein, a numerical solution model for parameterization of pipeline stress-strain response under the action of displacement caused by thawing settlement was established with the nonlinear finite element program ABAQUS and the INP programming language. The accuracy of model was verified with the test results. Meanwhile, the distribution characteristics of pipeline strain were studied through the analysis of influencing factors. The results show that: for X65 pipeline passing through the ice-rich permafrost area where the thawing settlement area is in small width, the maximum axial strain is located in the center of the thawing settlement area, and the tensile strain of the pipeline is greater than the compressive strain, so that the entire pipeline is in the state of tension. However, when the thawing settlement area is wider than 60 m, the pipeline is subjected to thawing settlement together with the ground, with bending strain as the maximum strain, which is located at the edge of the thawing settlement area. Besides, the widening of thawing settlement area will not affect the pipeline strain significantly. Therefore, attention should be paid to the identification of the range of thawing settlement areas in the geohazard monitoring. Generally, for the thawing settlement areas with small width, pipeline strain in the center and edge of thawing settlement areas should be monitored, while for those thawing settlement areas with width larger than 60 m, the pipeline strain at the edge of thawing settlement areas should be monitored.

Abstract Gastric cancer (GC) is the second cause of cancer-related death and metastasis is an important cause of death. Considering difficulties in searching for metastatic driver mutations, we tried a novel strategy here. We conducted an integrative genomic analysis on GC and identified early drivers lead to metastasis. Whole-exome sequencing (WES), transcriptomes sequencing and targeted-exome sequencing (TES) were performed on tumors and matched normal tissues from 432 Chinese GC patients, especially the comparative analysis between higher metastatic-potential (HMP) group with T1 stage and lymph-node metastasis, and lower metastatic-potential (LMP) group without lymph-nodes or distant metastasis. HMP group presented higher mutation load and heterogeneity, enrichment in immunosuppressive signaling, more immune cell infiltration than LMP group. An integrated mRNA-lncRNA signature based on differentially expressed genes was constructed and its prognostic value was better than traditional TNM stage. We identified 176 candidate prometastatic mutations by WES and selected 8 genes for following TES. Mutated TP53 and MADCAM1 were significantly associated with poor metastasis-free survival. We further demonstrated that mutated MADCAM1 could not only directly promote cancer cells migration, but also could trigger tumor metastasis by establishing immunosuppressive microenvironment, including promoting PD-L1-mediated immune escape and reprogramming tumor-associated macrophages by regulating CCL2 through Akt/mTOR axis. In conclusion, GCs with different metastatic-potential are distinguishable at the genetic level and we revealed a number of potential metastatic driver mutations. Driver mutations in early-onset metastatic GC could promote metastasis by establishing an immunosuppressive microenvironment. This study provided possibility for future target therapy of GC.

Abstract Objective To describe the clinical outcome and physical condition of patients with locally advanced breast cancer (LABC) who received neoadjuvant chemotherapy followed by mastectomy and latissimus dorsi myocutaneous flap repair. Methods A retrospective review of 142 patients with locally advanced breast cancer was selected from 1156 breast cancer patients in the South and North areas of The Affiliated Calmette Hospital of Kunming Medical University between May 2008 and December 2018. Results All participants (n = 142) were women aged 40–55 years (average age 47.35 ± 0.43 years) who received neoadjuvant chemotherapy followed by mastectomy and latissimus dorsi flap repair. The median follow-up period was 16 months (range 12–24 months). For stage of disease, there were 19 cases (13%) in stage IIB, 31 cases (22%) in stage IIIA, 39 cases (28%) in stage IIIB, and 53 cases (37%) in stage IIIC, which were statistically significant with the physical condition of patients (≤ 0.001). Neoadjuvant chemotherapy was administered to shrink the tumors, and an average tumor size decrease from 10.05 ± 1.59 cm × (8.07 ± 1.54) cm to 6.11 ± 1.72 cm × (3.91 ± 1.52) cm (P < 0.001) was considered statistically significant. A t test was used for the ECOG score statistics, and the results showed that the scores were statistically significant (≤ 0.001) before and after neoadjuvant chemotherapy and after surgery. Conclusions Neoadjuvant chemotherapy is an accepted treatment option for patients with locally advanced breast cancer, and the use of a latissimus dorsi musculocutaneous flap for post-mastectomy reconstruction may improve the patients’ physical condition. Our results indicated that this strategy was safe and feasible.

X-ray source based on the Thomson scattering of laser interacting with energetic electron beams features high photon energy, small spot size, and good collimation. However, the photon number is insufficient for practical application because of the small cross section of the Thomson scattering. To solve this problem, here, we replace a traditional Gaussian laser pulse with a flying focus laser pulse to extend interaction length and restrain nonlinear effects. Simulation results show that the scattered photon number can be increased by about 25 and 2 times for high and low energy lasers, respectively. In particular, a 1010 photon number can be generated with a 10 J flying focus laser pulse, and the energy spread can also be greatly reduced for high energy laser, from a broad spectrum to a monoenergetic peak. Combining these two advantages, the peak spectrum brightness of x ray is 3 × 108 photons/keV at 240 keV, which is about three orders of magnitude more than the traditional case.

BackgroundThe close relationship between ankylosing spondylitis (AS) and inflammatory bowel diseases (IBD) has been supported by many aspects, including but not limited to clinical manifestations, epidemiology and pathogenesis. Some evidence suggests that immune cells actively participated in the pathogenesis of both diseases. However, information on which cells are primarily involved in this process and how these cells mobilize, migrate and interact is still limited.MethodsDatasets were downloaded from Gene Expression Omnibus (GEO) database. Common differentially expressed genes (coDEGs) were identified by package “limma”. The protein-protein interaction (PPI) network and Weighted Gene Co-Expression Network Analysis (WGCNA) were used to analyze the interactions between coDEGs. KEGG pathway enrichment analysis and inverse cumulative distribution function were applied to identify common differential pathways, while Gene Set Enrichment Analysis (GSEA) was used to confirm the significance. Correlation analysis between coDEGs and immune cells led to the identification of critical immune-cell-related coDEGs. The diagnostic models were established based on least absolute shrinkage and selection operator (LASSO) regression, while receiver operating characteristic (ROC) analysis was used to identify the ability of the model. Validation datasets were imported to demonstrate the significant association of coDEGs with specific immune cells and the capabilities of the diagnostic model.ResultsIn total, 67 genes were up-regulated and 185 genes were down-regulated in both diseases. Four down-regulated pathways and four up-regulated pathways were considered important. Up-regulated coDEGs were firmly associated with neutrophils, while down-regulated genes were significantly associated with CD8+ T−cells and CD4+ T−cells in both AS and IBD datasets. Five up-regulated and six down-regulated key immue-cell-related coDEGs were identified. Diagnostic models based on key immue-cell-related coDEGs were established and tested. Validation datasets confirmed the significance of the correlation between coDEGs and specific immune cells.ConclusionThis study provides fresh insights into the co-pathogenesis of AS and IBD. It is proposed that neutrophils and T cells may be actively involved in this process, however, in opposite ways. The immue-cell-related coDEGs, revealed in this study, may be relevant to their regulation, although relevant research is still lacking.

Candida albicans (C. albicans) is an opportunistic pathogenic fungus that often causes mucosal and systemic infections. Several pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), have been implicated in the host recognition of C. albicans. These PRRs recognize the pathogen-associated molecular patterns (PAMPs) of C. albicans to activate innate immune cells, thereby rapidly inducing various inflammatory responses by activating intracellular signaling cascades. Herbal medicine and its active components deserve priority development due to their low toxicity and high antibacterial, antiviral and antifungal activities. This review discussed the activities of herbal compounds against C. albicans and their related mechanisms, especially their regulatory role on innate immune cells such as neutrophils, macrophages, and dendritic cells (DCs) implicated in C. albicans infections. Our work aims to find new therapeutic drugs and targets to prevent and treat diseases caused by C. albicans infection with the mechanisms by which this fungus interacts with the innate immune response.

Summary: Background: Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic within-class targeted anticancer drugs are approved in China, it is expected that this may reduce the price of novel anticancer drugs and improve the affordability of anticancer drugs. This study aimed to evaluate the price, efficacy, and safety of the within-class anticancer drugs between domestic and imported drugs approved in China from 2010 to 2022. Methods: The domestic and imported within-class targeted drugs for solid cancers approved in China between 2010 and 2022 were extracted. We classified it as a class of anticancer drugs based on the same indication and similar biological mechanism. The published literature derived from pivotal clinical trials of these domestic and imported drugs was identified based on the review report and the latest labels issued by the China National Medical Products Administration. We evaluated the monthly treatment price at launch and the latest (2022), primary efficacy endpoint and safety between domestic and imported anticancer drugs. Meta-analyses were further employed to evaluate the efficacy and safety of the domestic and imported anticancer drugs, including pooled hazard ratios (HR) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR) for solid cancers, and relative risk for serious adverse events (SAE) and Grade ≥3 adverse events (AEs). Findings: In our cohort study, 12 within-class anticancer drugs with 7 cancer diseases were analyzed, including 18 domestic (21 indications; 21 pivotal trials) and 18 imported (21 indications; 27 pivotal trials) novel anticancer drugs, respectively. The median monthly treatment price of domestic and imported drugs from the years of launch to 2022 had significantly decreased by 71% and 62%, respectively. Moreover, the median monthly treatment price of domestic targeted anticancer drugs on the market at launch ($3786 vs. $5393, P = 0.007) and the latest ($1222 vs. $2077, P = 0.011) was significantly lower than that of imported drugs. No significant differences in median PFS gains (9.0 vs. 11.0 months; P = 0.24), OS gains (9.3 vs 10.6 months; P = 0.66), and ORR (57% vs 62%, P = 0.77) of targeted anticancer drugs in their pivotal trials were observed between the domestic and imported drugs. Additionally, there was no significant difference between domestic and imported drugs in the incidence of SAE (23% vs. 24%; P = 0.41) and Grade ≥3 AEs (59% vs. 57%; P = 0.45). These findings were also further confirmed in the meta-analyses for primary efficacy endpoints and safety outcomes. Interpretation: The prices of both domestic and imported anticancer drugs significantly decreased after market entry mainly due to the role of national price negotiations. The median monthly treatment price of domestic within-class targeted anticancer drugs was significantly lower than that of imported drugs. Furthermore, the efficacy and safety of domestic anticancer drugs were comparable to that of imported drugs. This evidence implicated that the development of within-class anticancer drugs with national price negotiations in China significantly improved the affordability for patients. Funding: This study was supported by postdoctoral fellowship from Tsinghua-Peking Joint Centers for Life Sciences (CLS).

Osteoarthritis (OA) is a degenerative disease that is difficult to cure owing to its complicated pathogenesis. Exercise therapy has been endorsed as a primary treatment option. However, it remains controversial how exercise intensity regulates OA progression. Here, a declining propensity for TGF-β1 was predicted via bioinformatics analysis of microarray GSE57218 and validated in cartilage samples obtained from arthroplasty. Based on this, cyclic tensile strain or TGF-β1 intervention was performed on human OA chondrocytes, and we found that moderate-intensity mechanical loads protected chondrocytes against pyroptosis. During this process, the elevation of TGF-β1 is mechanically stimuli-dependent and exerts an inhibitory effect on chondrocyte pyroptosis. Moreover, we elucidated that TGF-β1 activated Smad2/3 and inhibited the NF-κB signaling pathway to suppress chondrocyte pyroptosis. Furthermore, we established a rat knee OA model by intra-articular injection of monosodium iodoacetate and performed treadmill exercises of different intensities. Similar to the in vitro results, we demonstrated that moderate-intensity treadmill exercise had an outstanding chondroprotective effect. An inappropriate intensity of mechanical stimulation may aggravate OA both in vivo and in vitro. Overall, our findings demonstrated that activation of the TGF-β1/Smad2/Smad3 axis and inhibition of NF-κB coordinately inhibit chondrocyte pyroptosis under mechanical loads. This study sheds light on the future development of safe and effective exercise therapies for OA.

Introduction: Achieving a successful reconstruction of alveolar bone morphology still remains a challenge because of the irregularity and complex microenvironment of tooth sockets. Biological materials including hydroxyapatite and collagen, are used for alveolar ridge preservation. However, the healing effect is often unsatisfactory.Methods: Inspired by superwetting biomimetic materials, we constructed a 3D actively-spreading bone repair material. It consisted of photocurable polyether F127 diacrylate hydrogel loaded with mixed spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs).Results: Biologically, cells in the spheroids were able to spread and migrate outwards, and possessed both osteogenic and angiogenic potential. Meanwhile, ECs also enhanced osteogenic differentiation of MSCs. Mechanically, the excellent physical properties of F127DA hydrogel ensured that it was able to be injected directly into the tooth socket and stabilized after light curing. In vivo experiments showed that MSC-EC-F127DA system promoted bone repair and preserved the shape of alveolar ridge within a short time duration.Discussion: In conclusion, the novel photocurable injectable MSC-EC-F127DA hydrogel system was able to achieve three-dimensional tissue infiltration, and exhibited much therapeutic potential for complex oral bone defects in the future.

Many carbon-related physiological questions in plants such as carbon (C) limitation or starvation have not yet been resolved thoroughly due to the lack of suitable experimental methodology. As a first step towards resolving these problems, we conducted infusion experiments with bonsai trees (Ficus microcarpa) and young maple trees (Acer pseudoplatanus) in greenhouse, and with adult Scots pine trees (Pinus sylvestris) in the field, that were “fed” with 13C-labelled glucose either through the phloem or the xylem. We then traced the 13C-signal in plant organic matter and respiration to test whether trees can take up and metabolize exogenous sugars infused. Ten weeks after infusion started, xylem but not phloem infusion significantly increased the δ13C values in both aboveground and belowground tissues of the bonsai trees in the greenhouse, whereas xylem infusion significantly increased xylem δ13C values and phloem infusion significantly increased phloem δ13C values of the adult pines in the field experiment, compared to the corresponding controls. The respiration measurement experiment with young maple trees showed significantly increased δ13C-values in shoot respired CO2 at the time of four weeks after xylem infusion started. Our results clearly indicate that trees do translocate and metabolize exogenous sugars infused, and because the phloem layer is too thin, and thus xylem infusion can be better operated than phloem infusion. This tree infusion method developed here opens up new avenues and has great potential to be used for research on the whole plant C balance and its regulation in response to environmental factors and extreme stress conditions.

The uncertainty caused by the growing use of renewable energy sources, such as wind and solar energy, makes it difficult to forecast the operation costs of micro-energy systems, particularly those in remote rural areas. Motivated by this point, this paper analyzes the possible operational risks and then introduces Condition Value at Risk (CVaR) to quantify the cost of the operational risk. On this basis, stochastic programming based on a multi-energy microgrid planning model that minimizes the investment cost, the operating cost, and the cost of operational risk, while considering the physical limitations of the multi-energy microgrid, is presented. Especially, scenarios of wind and solar energy output are generated using the Latin hypercube sampling method and reduced using the crowding measure-based scenario reduction method. After piecewise linearization and second-order cone relaxation, the model proposed in this paper is processed as a mixed integer linear model and solved by CPLEX. According to the achieved typical scenarios processed by the reduction method, the simulation shows that the presented configuration model can balance the investment cost and the cost of the operational risk, which effectively enhances the system’s ability to cope with uncertainties and fluctuations. Moreover, by adjusting the risk preference coefficient, the conservativeness of the planning scheme can be correspondingly adjusted.

Osteoarthritis (OA) is one of the most common refractory degenerative joint diseases worldwide. Synovitis is believed to drive joint cartilage destruction during OA pathogenesis. Cuproptosis is a novel form of copper-induced cell death. However, few studies have examined the correlations between cuproptosis-related genes (CRGs), immune infiltration, and synovitis. Therefore, we analyzed CRGs in synovitis during OA. Microarray datasets (GSE55235, GSE55457, GSE12021, GSE82107 and GSE176308) were downloaded from the Gene Expression Omnibus database. Next, we conducted differential and subtype analyses of CRGs across synovitis. Immune infiltration and correlation analyses were performed to explore the association between CRGs and immune cell abundance in synovitis. Finally, single-cell RNA-seq profiling was performed using the GSE176308 dataset to investigate the expression of CRGs in the various cell clusters. We found that the expression of five CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) was significantly increased in the OA synovium. Moreover, abundant and various types of immune cells infiltrated the synovium during OA, which was correlated with the expression of CRGs. Additionally, single-cell RNA-seq profiling revealed that the cellular composition of the synovium was complex and that their proportions varied greatly as OA progressed. The expression of CRGs differed across various cell types in the OA synovium. The current study predicted that cuproptosis may be involved in the pathogenesis of synovitis. The five screened CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) could be explored as candidate biomarkers or therapeutic targets for OA synovitis.

The production of metrnl, a novel adipomyokine, is induced upon exercise in adipose tissue and skeletal muscle. In this study, we investigated the anti-inflammatory and antipyroptotic effects of exercise-induced metrnl producted in rats in vitro and in vivo. Forty Sprague-Dawley rats were divided randomly into five groups: control (CG), osteoarthritis (OA) with sedentary lifestyle (OAG), OA with low intensity exercise (OAL), OA with moderate intensity exercise (OAM), and OA with high intensity exercise (OAH). The correlation between the level of metrnl and OA degree was detected using ELISA, X-ray imaging, histology, and immunohistochemistry in vivo. Primary chondrocytes were preincubated with recombinant metrnl before interleukin-1β administration to verify the anti-inflammatory and antipyroptotic effects of metrnl. Western blotting and quantitative reverse transcription (qRT)-PCR were used to evaluate the differences in protein and mRNA expression between groups, respectively. Reactive oxygen species (ROS) assay, immunofluorescence, transmission electron microscopy (TEM), and flow cytometry were used to evaluate morphological changes and pyroptosis in chondrocytes. In the moderate-intensity treadmill exercise group, the severity of OA showed maximum relief and the metrnl levels had the most significant increase. Metrnl exerted its anti-inflammatory effect through the suppression of the PI3K/Akt/NF-κB pathway in IL-1β-induced OA chondrocytes, which was accompanied with the recovery of collagen II expression and the attenuation of MMP13 and ADAMTS5. Moreover, metrnl ameliorated chondrocyte pyroptosis by inhibiting the activation of the nod-like receptor protein-3/caspase-1/gasdermin D cascade. In conclusion, moderate-intensity exercise improves inflammation and pyroptosis by increasing metrnl release, which inhibits the PI3K/Akt/NF-κB and further NLRP3/caspase-1/GSDMD signaling pathways.

As shale gas reservoirs have low porosity and low permeability, hydraulic fracturing is a necessary means for industrial exploitation of shale gas. In this study, aiming at the problem of reservoir damage in the process of hydraulic fracturing of shale gas reservoir, a physical simulation method of slickwater fracturing fluid flow in shale core has been established. The change laws of physical parameters of the shale were quantified after slickwater fracturing fluid filtrating into it. The main factors affecting physical parameters of shale matrix around fractures were found out in the process of fracturing, shut-in, and flowback of slickwater fracturing fluid. The results show that after treated by slickwater fracturing fluid, the wettability of shale becomes more uniform in distribution (the water contact angles from 43° to 48°). In the fracturing filtration zone, the damage rate of fracturing fluid to shale porosity is 6.4%-42.0%. Low differential pressure flowback can reduce the damage of the shale, and prolonging the time of shut-in has no obvious effect on the damage to porosity. After 0.3 d (imbibition stability time), the damage of fracturing fluid to shale permeability is basically stable (55.9%). Permeability damage is mainly caused by residue of the fracturing fluid in large pores and bound water in small pores. Analysis of weights of all fracturing parameters shows that flowback differential pressure has the largest influence weight on shale porosity (51.4%), and well shut-in time has the largest influence weight on shale permeability (62.7%). Therefore, in the production process, it is suggested to properly reduce the backflow differential pressure and moderately shorten the well shut-in time.

We review the progress on the applications of the vortex-surface field (VSF). The VSF isosurface is a vortex surface consisting of vortex lines. Based on the generalized Helmholtz theorem, the VSF isosurfaces of the same threshold at different times have strong coherence. As a general flow diagnostic tool for studying vortex evolution, the numerical VSF solution is first constructed in a given flow field by solving a pseudo-transport equation driven by the instantaneous frozen vorticity, and then the VSF evolution is calculated by the two-time method. From the database of numerical simulations or experiments, the VSF can elucidate mechanisms in the flows with essential vortex dynamics, such as isotropic turbulence, wall flow transition, flow past a flapping plate and turbulence–flame interaction. The characterization of VSFs reveals the correlation between robust statistical features and the critical quantities needed to be predicted in engineering applications, such as the friction coefficient in transition, thrust in bio-propulsion and growth rate in interface instability. Since the VSF evolution captures the essential Lagrangian-based dynamics of vortical flows, it inspires novel numerical methods on cutting-edge hardware, e.g. graphic and quantum processors.

Landslide-induced impulse waves in alpine valleys are a significant risk to large-scale dam and reservoir engineering projects in the surrounding area. In this study, a 1 : 200-scale physical model of landslide-induced impulse waves in a V-shaped river channel was established, and 18 groups of tests were conducted to evaluate the influence of different parameters, such as the volume and shape of the landslide body, water entry velocity, and water depth of the reservoir. Based on the test results, a dimensionless formula was established for the first wave height of impulse waves caused by a deep-water landslide in a V-shaped channel. An energy conversion law was determined for the impact of landslide-induced impulse waves on the reservoir bank. Finally, a distribution law was obtained for the initial maximum pressure caused by landslide-induced impulse waves along the water depth on the opposite bank. The theoretical predictions of the dimensionless formula showed good agreement with the experimental results, and the energy conversion rate of the landslide-induced impulse waves initially increased and then decreased with an increasing Froude number. The maximum dynamic water pressure showed a triangular distribution with increasing water depth below the surface of the still water body. The impact pressure of the impulse waves on the slope on the opposite bank increased with the water entry velocity. This study provides a scientific basis for the risk prevention and control of landslide-induced impulse waves in river channels feeding into reservoirs.

PurposeTuberculosis is common infectious diseases, characterized by infectivity, concealment and chronicity, and the early diagnosis is helpful to block the spread of tuberculosis and reduce the resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs. At present, there are obvious limitations in the application of clinical detection methods used for the early diagnosis of tuberculosis. RNA sequencing (RNA-Seq) has become an economical and accurate gene sequencing method for quantifying transcripts and detecting unknown RNA species.MethodsA peripheral blood mRNA sequencing was used to screen the differentially expressed genes between healthy people and tuberculosis patients. A protein-protein interaction (PPI) network of differentially expressed genes was constructed through Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The potential diagnostic targets of tuberculosis were screened by the calculation of degree, betweenness and closeness in Cytoscape 3.9.1 software. Finally, the functional pathways and the molecular mechanism of tuberculosis were clarified in combination of the prediction results of key gene miRNAs, and by Gene Ontology (GO) enrichment analysis and the Kyoto Encyclopedia Genes and Genomes (KEGG) pathway annotation analysis.Results556 Differential genes of tuberculosis were screened out by mRNA sequencing. Six key genes (AKT1, TP53, EGF, ARF1, CD274 and PRKCZ) were screened as the potential diagnostic targets for tuberculosis by analyzing the PPI regulatory network and using three algorithms. Three pathways related to the pathogenesis of tuberculosis were identified by KEGG pathway analysis, and two key miRNAs (has-miR-150-5p and has-miR-25-3p) that might participate in the pathogenesis of tuberculosis were screened out by constructing a miRNA-mRNA pathway regulatory network.ConclusionSix key genes and two important miRNAs that could regulate them were screened out by mRNA sequencing. The 6 key genes and 2 important miRNAs may participate in the pathogenesis of infection and invasion of Mycobacterium tuberculosis through herpes simplex virus 1 infection, endocytosis and B cell receptor signaling pathways.

The combined usage of phasor measurement units and machine learning algorithms provides the opportunity for developing response-based wide-area system integrity protection scheme against transient instability in power systems. However, only the transient stability status is usually predicted in the literature, which is not enough for real-time decision-making for response-based emergency control. In this paper, an integrated approach is proposed. The GRU-based predictor is firstly proposed for post-disturbance transient stability prediction. On this basis, a multi-task learning framework is proposed for the identification of unstable machines and also the estimation of generation shedding. Case study on the IEEE 39-bus system demonstrates that, apart from the basic task of transient stability prediction, the proposed GRU-based multi-task predictor can predict the grouping of unstable machines correctly. Moreover, based on the estimated amount of generation shedding, the generated remedial control actions can retain the synchronism of the power system.

1,5-Pentanediamine hydrochloride (PDAH) was an important raw material for the preparation of bio-based pentamethylene diisocyanate (PDI). PDI has shown excellent properties in the application of adhesives and thermosetting polyurethane. In this study, PDAH was recovered from 1,5-pentanediamine (PDA) fermentation broth using a cation exchange resin and purified by crystallization. D152 was selected as the most suitable resin for purifying PDAH. The effects of solution pH, initial temperature, concentration of PDA, and adsorption time were studied by the static adsorption method. The equilibrium adsorption data were well fitted to Langmiur, Freundlich, and Temkin-Pyzhev adsorption isotherms. The adsorption free energy, enthalpy, and entropy were calculated. The experimental data were well described by the pseudo first-order kinetics model. The dynamic experiment in the fixed bed column showed that under optimal conditions, the adsorption capacity reached 96.45 mg g−1, and the recovery proportion of the effective section reached 80.16%. In addition, the crystallization of the PDAH solution obtained by elution proved that the crystal product quality of resin eluting solution was highest. Thus, our research will contribute to the industrial scale-up of the separation of PDAH.

Coronavirus disease 2019, responsible for a global pandemic, is caused by the severe acute respiratory syndrome coronavirus 2. Several vaccines have been developed and approved worldwide, particularly in China. As of Oct 17, 2021, four new coronavirus vaccines in China have been conditionally approved for marketing by the National Medical Products Administration, two of which have been authorized for emergency use in the Emergency Use Listing of the World Health Organization. Domestic vaccine R&D in China has relied on legal and regulatory support. This article summarizes the regulatory policy for vaccine development, review and approval. Vaccine approval laws have been continually improved, and regulations for special approval have been used to shorten the review time. China has coordinated pandemic-related needs, both domestically and with other countries, and made substantial progress in cooperative international anti-pandemic efforts.

Measurement(s) building rooftop area Technology Type(s) computational modeling technique Sample Characteristic - Environment city Sample Characteristic - Location China