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The investigation and research of the distribution, biological characteristics, water environment and sediment environmental elements of the seagrass bed in Caofeidian was conducted to define the distribution area of the seagrass bed, classify its coverage, analyze and study the ecological characteristics of the seagrass bed and the characteristics of key environmental impact factors. This provides technical references for understanding the resource and environmental background of the Caofeidian seagrass bed, delimiting the protection area, marine ecological restoration, and blue carbon research. The results show that the dominant species of the Caofeidian seagrass bed is eelgrass, The average plant height is 75.00±6.15 cm/shoot. Moreover, there are differences among different sites. The overall average stem density is 261.26±48.50 shoots/m2, and the total average aboveground and belowground biomass are 302.53±71.79 g DW/m2 and 114.71±27.40 g DW/m2, respectively. The distribution area of the seagrass bed is 42.90 km2, with dense area, relatively dense area, general area, relatively sparse area and sparse area accounting for 13.09%, 12.93%, 18.82%, 18.75% and 36.40%, respectively. The seagrass is distributed in two regions, northern and southern, with dense area and relatively dense area mostly distributed in the northern region. The difference in water environment between the grass bed area and the bare sand area is not significant, while the difference in sediment environment between the grass bed area and the bare sand area is significant. Water temperature, nutrient salts, transparency, water flow, and human engineering activities are key factors that affect the growth of seagrass in the Caofeidian sea area.

Abstract Background Eicosapentaenoic acid (EPA) is widely used in the functional food and nutraceutical industries due to its important benefits to human health. Oleaginous microorganisms are considered a promising alternative resource for the production of EPA lipids. However, the storage of EPA in triglyceride (TG) becomes a key factor limiting its level. Results This study aimed to incorporate more EPA into TG storage through metabolic engineering. Firstly, key enzymes for TG synthesis, the diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (GPAT) genes from Schizochytrium sp. HX-308 were expressed in Yarrowia lipolytica to enhance lipid and EPA accumulation. In addition, engineering the enzyme activity of DGATs through protein engineering was found to be effective in enhancing lipid synthesis by replacing the conserved motifs “HFS” in ScDGAT2A and “FFG” in ScDGAT2B with the motif “YFP”. Notably, combined with lipidomic analysis, the expression of ScDGAT2C and GPAT2 enhanced the storage of EPA in TG. Finally, the accumulation of lipid and EPA was further promoted by identifying and continuing to introduce the ScACC, ScACS, ScPDC, and ScG6PD genes from Schizochytrium sp., and the lipid and EPA titer of the final engineered strain reached 2.25 ± 0.03 g/L and 266.44 ± 5.74 mg/L, respectively, which increased by 174.39% (0.82 ± 0.02 g/L) and 282.27% (69.70 ± 0.80 mg/L) compared to the initial strain, respectively. Conclusion This study shows that the expression of lipid synthesis genes from Schizochytrium sp. in Y. lipolytica effectively improves the synthesis of lipids and EPA, which provided a promising target for EPA-enriched microbial oil production.

Abstract Background Microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) is known for its heightened responsiveness to immunotherapy. However, establishing robust predictive markers for immunotherapy efficacy remains imperative. This retrospective study aimed to elucidate the genetic landscape of MSI‐H CRC and correlate these genetic alterations with immunotherapy outcomes in a cohort of 121 patients. Methods We analyzed clinical and molecular data from 121 patients with MSI‐H CRC. We conducted a thorough genetic analysis of MSI‐H CRC patients, with a specific emphasis on the APC, TP53, RAS, and MMR genes. We further analyzed the relationship between gene mutations and immunotherapy efficacy. The primary endpoints analyzed were objective response rate (ORR) and progression‐free survival (PFS). All statistical analysis was conducted using SPSS26.0 and R 4.2.0 software. Results Our findings underscored the complexity of the genetic landscape in MSI‐H CRC, shedding light on the intricate interplay of these genes in CRC development. Notably, mutations in MMR genes exhibited a distinctive pattern, providing insights into the underlying mechanisms of MSI‐H. Furthermore, our results revealed correlations between specific genetic alterations and immunotherapy outcomes, with a particular focus on treatment response rates and progression‐free survival. Conclusion This study represents a significant step toward unraveling the genetic nuances of MSI‐H CRC. The distinctive pattern of MMR gene mutations not only adds depth to our understanding of MSI‐H CRC but also hints at potential avenues for targeted therapies. This research sets the stage for future investigations aimed at refining therapeutic strategies and improving outcomes for patients with MSI‐H CRC.

Abstract Currently, studies of ancient faunal community networks have been based mostly on uniformitarian and functional morphological evidence. As an important source of data, taphonomic evidence offers the opportunity to provide a broader scope for understanding palaeoecology. However, palaeoecological research methods based on taphonomic evidence are relatively rare, especially for body fossils in lacustrine sediments. Such fossil communities are not only affected by complex transportation and selective destruction in the sedimentation process, they also are strongly affected by time averaging. Historically, it has been believed that it is difficult to study lacustrine entombed fauna by a small-scale quadrat survey. Herein, we developed a software, the TaphonomeAnalyst, to study the associational network of lacustrine entombed fauna, or taphocoenosis. TaphonomeAnalyst allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. The dataset for these investigations resulted from fieldwork of the latest Middle Jurassic Jiulongshan Formation near Daohugou Village, in Ningcheng County of Inner Mongolia, China, spotlighting the core assemblage of the Yanliao Fauna. Our data included 27,000 fossil specimens of animals from this deposit, the Yanliao Fauna, whose analyses reveal sedimentary environments, taphonomic conditions, and co-occurrence networks of this highly studied assemblage, providing empirically robust and statistically significant evidence for multiple Yanliao habitats.

With the increasing consumer focus on automotive safety, Autonomous Emergency Braking (AEB) systems, recognized as effective active safety technologies for collision avoidance and the mitigation of collision-related injuries, are gaining wider application in the automotive industry. To address the issues of the insufficient working reliability of AEB systems and their unsatisfactory level of accordance with the psychological expectations of drivers, this study proposes an optimized second-order Time to Collision (TTC) safety time algorithm based on the motion state of the preceding vehicle. Additionally, the study introduces a safety distance algorithm derived from an analysis of the braking process of the main vehicle. The safety time algorithm focusing on comfort and the safety distance algorithm focusing on safety are effectively integrated in the time domain and the space domain to obtain the safety time–safety distance fusion algorithm. A MATLAB/Simulink–Carsim joint simulation platform has been established to validate the AEB control strategy in terms of safety, comfort, and system responsiveness. The simulation results show that the proposed safety time–safety distance fusion algorithm consistently achieves complete collision avoidance, indicating a higher safety level for the AEB system. Furthermore, the application of active hierarchical braking minimizes the distance error, at under 0.37 m, which meets psychological expectations of drivers and improves the comfort of the AEB system.

Abstract Background Nitrogen- and water-use efficiency (NUE and WUE) reflect the capacity of plants to take up and utilize resources in the environments. Although N deposition and drought are known to affect plant growth and persistence, it remains elusive how plants adjust NUE, WUE and their relationship to adapt to the concurrent N deposition and drought under the context of global change. We conducted a field experiment in a temperate grassland in Inner Mongolia, in which N addition (10 g m– 2 yr−1), drought (reduced 66% precipitation during growing season) and their combination were manipulated, and we explored the responses of both instantaneous (NUEINST and WUEINST) and long-term (NUELT and WUELT) WUE and NUE for six common plant species (Leymus chinensis, Stipa baicalensis, Thermopsis lanceolata, Potentilla bifurca, Thalictrum squarrosum, Klasea centauroide). Results Across all the six species, NUEINST decreased and WUEINST increased with both N addition and drought; NUELT decreased with both N addition and drought, while WUELT decreased with N addition and increased with drought. A significant interactive effect between N addition and drought was detected, in that, drought weakened the negative effect of N addition on WUELT and NUELT, and N addition weakened the negative effect of drought on NUELT, but enhanced the positive effect of drought on WUELT. As a consequence, drought caused a trade-off between NUE and WUE, and N addition brought forth positive correlation between NUE and WUE. Meanwhile, the relationship between NUE and WUE varied among the species of different functional groups. Conclusions Our study demonstrated that NUE, WUE and their relationship play an important role in determining their responses and adaptability to changes in soil nitrogen and water availability induced by N deposition and drought. Our results shed light on the antagonistic, synergetic and neutral effects between nitrogen deposition and drought on resource use efficiency, and further clarified the different adaptability among species of different functional groups, which will conduce to a comprehensive understanding on the role of NUE and WUE in plant persistence and coexistence in grassland ecosystems.

The natural color of biological specimens plays a crucial role in body protection, signaling, physiological adaptations, etc. Full-color optical sectioning structured illumination microscopy (OS-SIM) color is a promising approach that can reconstruct biological specimens in three-dimension meanwhile maintaining their natural color. Full-color OS-SIM takes the advantages of rapid imaging speed, compatibility with fluorescence and non-fluorescence samples, compact configuration, and low cost. However, the commonly used HSV-RMS reconstruction algorithm for full-color OS-SIM faces two issues to be improved. One is the RMS (root-mean-square) OS reconstruction algorithm is prone to background noise, and the other is the reconstruction is bound in RGB and HSV color spaces, consuming more reconstructing time. In this paper, we propose a full-color Fourier-OS-SIM method that allows for the OS reconstruction using the high-frequency spectrum of the sample and thus is immune to the low-frequency background noise. The full-color Fourier-OS-SIM directly runs in the RGB color space, providing an easy way to restore the color information. Simulation and experiments with various samples (pollen grains and tiny animals) demonstrate that the full-color Fourier-OS-SIM method is superior to the HSV-RMS method regarding background noise suppression. Moreover, benefiting from the background noise suppression merit, the quantitative morphological height map analysis with the full-color Fourier-OS-SIM method is more accurate. The proposed full-color Fourier-OS-SIM method is expected to find broad applications in biological and industrial fields where the 3D morphology and the color information of objects both need to be recovered.

PurposeThe prognosis of liver cancer remains unfavorable nowadays, making the search for predictive biomarkers of liver cancer prognosis of paramount importance to guide clinical diagnosis and treatment. This study was conducted to explore more prognostic markers for most HCC.Patients and methodsA total of 330 patients were enrolled in this study according to the inclusion and exclusion criteria. Follow-up data were collected for all patients until the cutoff date of the study, February 2023. In addition, patient outcomes were assessed with progression-free survival (PFS) and overall survival (OS). All statistical analysis was conducted using R 4.2.0 software.ResultsUnivariate analysis illustrated that the GD [the product of gamma-glutamyl transpeptidase (GGT) concentration and D-dimer concentration, GD=GGT*D-dimer] levels were related to PFS (p

The MetE like complex is found to be capable of regulating the PKS system to produce EPA in Schizochytrium, with its activation regulating the expression of key enzymes, improving the efficiency of DHA and EPA production.

Abstract Background Schizochytrium sp. is a heterotrophic, oil-producing microorganism that can efficiently produce lipids. However, the industrial production of bulk chemicals using Schizochytrium sp. is still not economically viable due to high-cost culture medium. Replacing glucose with cheap and renewable lignocellulose is a highly promising approach to reduce production costs, but Schizochytrium sp. cannot efficiently metabolize xylose, a major pentose in lignocellulosic biomass. Results In order to improve the utilization of lignocellulose by Schizochytrium sp., we cloned and functionally characterized the genes encoding enzymes involved in the xylose metabolism. The results showed that the endogenous xylose reductase and xylulose kinase genes possess corresponding functional activities. Additionally, attempts were made to construct a strain of Schizochytrium sp. that can effectively use xylose by using genetic engineering techniques to introduce exogenous xylitol dehydrogenase/xylose isomerase; however, the introduction of heterologous xylitol dehydrogenase did not produce a xylose-utilizing engineered strain, whereas the introduction of xylose isomerase did. The results showed that the engineered strain 308-XI with an exogenous xylose isomerase could consume 8.2 g/L xylose over 60 h of cultivation. Xylose consumption was further elevated to 11.1 g/L when heterologous xylose isomerase and xylulose kinase were overexpressed simultaneously. Furthermore, cultivation of 308-XI-XK(S) using lignocellulosic hydrolysates, which contained glucose and xylose, yielded a 22.4 g/L of dry cell weight and 5.3 g/L of total lipid titer, respectively, representing 42.7 and 30.4% increases compared to the wild type. Conclusion This study shows that engineering of Schizochytrium sp. to efficiently utilize xylose is conducive to improve its utilization of lignocellulose, which can reduce the costs of industrial lipid production.

Abstract To reduce the inpatient mortality and improve the quality of hospital management, we explore the relationship between temperatures and in-hospital mortality in a large sample across 10 years in Nanjing, Jiangsu. We collected 10 years’ data on patient deaths from a large research hospital. Distributed lag non-linear model (DLNM) was used to find the association between daily mean temperatures and in-hospital mortality. A total of 6160 in-hospital deaths were documented. Overall, peak RR appeared at 8 °C, with the range of 1 to 20 °C having a significantly high mortality risk. In the elderly (age ≥ 65 years), peak RR appeared at 5 °C, with range − 3 to 21 °C having a significantly high mortality risk. In males, peak RR appeared at 8 °C, with the range 0 to 24 °C having a significantly high mortality risk. Moderate cold (define as 2.5th percentile of daily mean temperatures to the MT), not extreme temperatures (≤ 2.5th percentile or ≥ 97.5th percentile of daily mean temperatures), increased the risk of death in hospital patients, especially in elderly and male in-hospital patients.

The increasing integration of photovoltaic generators (PVGs) and the uneven economic development in different regions may cause the unbalanced spatial-temporal distribution of load demands in an urban distribution network (UDN). This may lead to undesired consequences, including PVG curtailment, load shedding, and equipment inefficiency, etc. Global dynamic reconfiguration provides a promising method to solve those challenges. However, the power flow transfer capabilities for different kinds of switches are diverse, and the willingness of distribution system operators (DSOs) to select them is also different. In this paper, we formulate a multi-objective dynamic reconfiguration optimization model suitable for multi-level switching modes to minimize the operation cost, load imbalance, and the PVG curtailment. The multi-level switching includes feeder-level switching, transformer-level switching, and substation-level switching. A novel load balancing index is devised to quantify the global load balancing degree at different levels. Then, a stochastic programming model based on selected scenarios is established to address the uncertainties of PVGs and loads. Afterward, the fuzzy c-means (FCMs) clustering is applied to divide the time periods of reconfiguration. Further-more, the modified binary particle swarm optimization (BPSO) and Cplex solver are combined to solve the proposed mixed-in-teger second-order cone programming (MISOCP) model. Numerical results based on the 148-node and 297-node systems are obtained to validate the effectiveness of the proposed method.

Abstract Background Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment. Results In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner. Conclusions This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level. Graphical Abstract

The folate receptor-positive circulating tumor cell (FR+-CTC) count can be used to improve the diagnosis rate of lung cancer. The lymphocyte count (LC) and derived neutrophil-to-lymphocyte ratio (dNLR) are involved in inflammatory processes. Whether the FR+-CTC count combined with the dNLR or LC is helpful for diagnosing lung cancer recurrence is not clear. Sixty-eight patients who were initially diagnosed with lung cancer and received first-line treatment were included. The clinicopathological characteristics, routine blood examination results and CTC examination results of the patients were collected. The role of the complete blood count and FR+-CTC count in lung cancer treatment response and prognosis was analyzed. The FR+-CTC count after treatment was significantly correlated with the T stage (p=0.005). Multivariate analysis showed that the pathological type and FR+-CTC count were independent predictors of disease-or progression-free survival (DFS/PFS) in patients with lung cancer (p=0.010 and p=0.030, respectively). The FR+-CTC count, LC and dNLR predicted the recurrence of lung cancer (sensitivity and specificity of the FR+-CTC count, 69.2% and 71.4%; the LC, 50.0% and 88.5%; and the dNLR, 50.0% and 88.1%, respectively). The FR+-CTC count combined with the LC or dNLR improved the diagnostic rate of lung cancer recurrence (sensitivity and specificity of the FR+-CTC count plus the LC, 53.8% and 90.5%, and the FR+-CTC count plus the dNLR, 73.1% and 73.8%, respectively). When these three indicators were combined to predict lung cancer recurrence, the AUC value was 0.817. The FR+-CTC count combined with the dNLR and/or LC after treatment can improve the diagnostic rate of lung cancer recurrence. A higher FR+-CTC count predicts worse DFS/PFS in patients with lung cancer.

Abstract Background The oleaginous microorganism Schizochytrium sp. is widely used in scientific research and commercial lipid production processes. However, low glucose-to-lipid conversion rate (GLCR) and low lipid productivity of Schizochytrium sp. restrict the feasibility of its use. Results Orlistat is a lipase inhibitor, which avoids triacylglycerols (TAGs) from hydrolysis by lipase. TAGs are the main storage forms of fatty acids in Schizochytrium sp. In this study, the usage of orlistat increased the GLCR by 21.88% in the middle stage of fermentation. Whereas the productivity of lipid increased 1.34 times reaching 0.73 g/L/h, the saturated fatty acid and polyunsaturated fatty acid yield increased from 21.2 and 39.1 to 34.9 and 48.5 g/L, respectively, indicating the advantages of using a lipase inhibitor in microbial lipids fermentation. Similarly, the system was also successful in Thraustochytrid Aurantiochytrium. The metabolic regulatory mechanisms stimulated by orlistat in Schizochytrium sp. were further investigated using transcriptomics and metabolomics. The results showed that orlistat redistributed carbon allocation and enhanced the energy supply when inhibiting the TAGs’ degradation pathway. Therefore, lipase in Schizochytrium sp. prefers to hydrolyze saturated fatty acid TAGs into the β-oxidation pathway. Conclusions This study provides a simple and effective approach to improve lipid production, and makes us understand the mechanism of lipid accumulation and decomposition in Schizochytrium sp., offering new guidance for the exploitation of oleaginous microorganisms.

As an effective strategy for oncotherapy, developing efficacious drug delivery systems for cancer combination therapy remains a major challenge. To improve nanodrug biocompatibility and composite function facilitating their clinical conversion application, a novel nanocarrier was presented by a facile method through conjugating humic acid with gadolinium ions to synthesize HA-Gd with good biocompatibility and dispersity. HA-Gd exhibited high photothermal conversion efficiency up to 38%, excellent photothermal stability, and high doxorubicin (DOX) loading capacity (93%) with pH-responsive release properties. HA-Gd loading DOX showed a combined chemo-photothermal inhibitory effect on tumor cells. Compared with lipid-DOX, HA-Gd-DOX had a more significant inhibitory effect on tumor growth and fewer side effects. T1-weighted MRI contrast toward tumor tissue provided HA-Gd with an MRI-based cancer diagnosis. This study revealed the great potential of humic acids as a novel vector for developing more drug carriers with desirable functions for clinical anticancer therapy.

Species diversity has been shown to be influenced by environmental factors, but the mechanism underlying their relationship remains unclear across spatial scales. Based on field investigation data collected from 3077 sample plots in temperate forest ecosystems, we compared tree species richness, evenness and dominance at 10 km × 10 km, 30 km × 30 km and 90 km × 90 km spatial scales. Then, we detected the scale dependence of changes in tree species composition on climate, topography and forest structure using variation partitioning and quantified their contribution to tree diversity with gradient–boosted models (GBMs) and fitted their relationships. The magnitude of tree richness, evenness and dominance significantly increased with spatial scale. Ecological factors jointly accounted for 24.3%, 26.5% and 38.5% of the variation in tree species composition at the three spatial scales, respectively. The annual mean temperature had a strong impact on tree richness, evenness and dominance and peaked at an intermediate scale. Tree evenness and dominance increased with the variation of temperature but had upper and lower limits. Tree richness obviously increased with annual precipitation on multiple scales and decreased with annual sunshine duration at large spatial scales. Tree richness, evenness and dominance obviously increased with the variation in elevation and diameter at breast height at large scales and small scales, respectively. Tree dominance decreased with tree height at a small scale. The dependence of tree diversity on ecological factors increased with spatial scales. Furthermore, different factors exert various controls on tree diversity at different spatial scales, representing a comprehensive mechanism regulating tree diversity.

As a branch of 3D microscopy, optical sectioning structured illumination microscopy (OS-SIM) has the advantages of fast imaging speed, weak photobleaching and phototoxicity, and flexible and compatible configuration. Although the method of using the one-dimensional periodic fringe pattern projected on the sample can remove the out-of-focus background from the in-focus signal, the axial resolution of the final reconstructed 3D image is not improved. Here, we propose a three-beam interference OS-SIM, namely TBOS, instead of the common-used dual-beam interference OS-SIM (DBOS). The three-beam interference scheme has been adopted in 3D super-resolution SIM (3D-SR-SIM), where the fringe phase shifting needs to be along each of the three orientations. In contrast, TBOS applies phase shifting only in one arbitrary direction. We built a TBOS SIM microscope and performed the 3D imaging experiments with 46 nm diameter fluorescent microspheres and a mouse kidney section. The axial resolution of the 3D image obtained with TBOS was enhanced by a factor of 1.36 compared to the DBOS method, consistent with the theoretical analysis and simulation. The OS-SIM with enhanced axial resolution for 3D imaging may find a wide range of applications in the biomedical field.

Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and in vitro cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance.

Abstract Background The dysregulation of gut microbiota is pivotal in colorectal carcinogenesis. Meanwhile, altered gut microbiome may affect the development of intestinal diseases through interaction with the host genes. However, the synergy between the altered gut microbiota composition and differential expression of specific genes in colorectal cancer (CRC) remains elusive. Thus, we integrated the data from 16S rRNA gene sequences and RNA sequences to investigate the potential relationship between genes and gut microbes in patients with CRC. Results Compared with normal samples, the presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicutes and Spirochaetes decreased markedly. In particular, the genera Fusobacterium, Catenibacterium, and Shewanella were only detected in tumor samples. Meanwhile, a closely interaction between Butyricimonas and Clostridium was observed in the microbiome network. Furthermore, a total of 246 (differentially expressed genes) DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, genes like cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and ATP binding cassette subfamily G member 2 (ABCG2) enriched in these two pathways were connected with the prognosis of CRC, and CRC patients with low expression level of CYP3A4 and ABCG2 had longer survival time. Conclusion Identifying the complicated interaction between gut microbiota and the DEGs contributed to further understand the pathogenesis of CRC, and these findings might enable better diagnosis and treatment of CRC patients.

Abstract Myeloid-derived suppressor cells (MDSCs) are notable contributors to the immunosuppressive tumor microenvironment (TME) and are closely associated with tumor progression; in addition, MDSCs are present in most patients with cancer. However, the molecular mechanisms that regulate MDSCs in the etiopathogenesis of human tumor immunity remain unclear. The secreted alarmin high mobility group box 1 (HMGB1) is a proinflammatory factor and inducer of many inflammatory molecules during MDSC development. In this review, we detail the currently reported characteristics of MDSCs in tumor immune escape and the regulatory role of secreted HMGB1 in MDSC differentiation, proliferation, activity and survival. Notably, different posttranslational modifications of HMGB1 may have various effects on MDSCs, and these effects need further identification. Moreover, exosome-derived HMGB1 is speculated to exert a regulatory effect on MDSCs, but no report has confirmed this hypothesis. Therefore, the effects of HMGB1 on MDSCs need more research attention, and additional investigations should be conducted.

ABSTRACTOn 31 December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, China, and caused the outbreak of the Coronavirus Disease 2019 (COVID-19). To date, computed tomography (CT) findings have been recommended as major evidence for the clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the imaging characteristics and changes throughout the disease course in patients with COVID-19 in order to provide some help for clinicians. Typical CT findings included bilateral ground-glass opacity, pulmonary consolidation, and prominent distribution in the posterior and peripheral parts of the lungs. This review also provides a comparison between COVID-19 and other diseases that have similar CT findings. Since most patients with COVID-19 infection share typical imaging features, radiological examinations have an irreplaceable role in screening, diagnosis and monitoring treatment effects in clinical practice.

Abstract Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

Globally, extreme droughts are likely to become more frequent, more intense, and longer in duration with climate change. Understanding the impacts of drought on ecosystem function (i.e., resistance) and its recovery after drought (i.e., resilience) is critical for long-term sustainability of ecosystem services under climate change. We tested the effects of drought duration on ecosystem resistance by imposing four years of extreme drought (

B4GALNT2 gene encodes the enzyme β1,4-N-acetylgalactosaminyltransferase 2 that biosynthesizes the histo-blood group antigen Sda, which is expressed on the surface of erythrocytes and in body secretions. Analysis of The Cancer Genome Atlas (TCGA) database revealed that this gene was highly expressed in breast cancer tissues in comparison with adjacent healthy ones. In-vitro lentivirus-assisted B4GALNT2 gene knockdown experiments in model triple negative breast cancer (TNBC) cell lines (HCC1937 and MDA-MB-231) showed inhibition in cell proliferation, decrease in cell viability, promotion of cell apoptosis and inhibitions in cell migration and invasiveness abilities in comparison with empty lentivirus transfectant controls. Also, in cell cycle tests, the number of cells in the G1 phase increased, in the S phase decreased and did not change in the G2/M phase (indicative of the presence of a block in the G1 phase). In-vivo tumor formation experiments in mice revealed that knockdown of the B4GALNT2 gene in MDA-MB-231 cells inhibited their proliferation. Using co-immunoprecipitation (Co-IP) mass spectroscopy-assisted analysis, it was found that HLA-B protein [a product of the human leukocyte antigen (HLA) class I gene] interacts with B4GALNT2 protein. In-vitro overexpression of HLA-B in B4GALNT2-knocked down MDA-MB-231 cell lines significantly recovered the cell proliferation, viability and migration ability of B4GALNT2 gene. These indicate that HLA-B is one of the interaction proteins in the downstream pathway of the B4GALNT2 gene.

Abstract Background Long noncoding RNA (lncRNA) has been implicated in numerous tumors, including pancreatic cancer (PC). However, the precise cellular roles and molecular mechanisms of lncRNA DIO3OS on PC development remains to be fully clarified. Methods We performed the meta-analysis on PC samples and non-tumor samples retrieved from the TCGA database, and measured the levels of DIO3OS in PC cell lines and a normal pancreatic duct epithelial cell line HPDE6-C7. Cell proliferation was evaluated via CCK-8 assay. Cell invasion in vitro was investigated by transwell assay. The RNA immunoprecipitation assay and luciferase reporter assay was utilized to confirm the putative miR-122-binding site in DIO3OS. The effects of DIO3OS on PC progression were tested using in vivo subcutaneous xenografts. Results Our results showed that DIO3OS was highly expressed in human PC tissues and PC cell lines. DIO3OS exhibited oncogenic properties in stimulating PC cell proliferation and invasion in vitro and promoting cancer growth in vivo. Through online predictive tools and functional experiments, we found that DIO3OS could bind directly to microRNA-122 (miR-122) and inhibited its expression, which functioned as a tumor suppressor in PC cells. We also verified that ALDOA was the direct target of miR-122, and the tumor suppressive effects caused by DIO3OS knockdown or miR-122 overexpression could be rescued by re-expression of ALDOA in PC cells. Conclusions Overall, our study suggested that lncRNA DIO3OS promotes PC cell growth and invasion by competing for miR-122 to modulate the expression of ALDOA. These findings yield a better understanding of the potential mechanisms by which gain of DIO3OS expression accelerates PC progression.

BackgroundBreast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients.MethodsSystematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores.ResultsOur study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model.ConclusionOur study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.

Background: Thymosin alpha-1 (TA) has been reported to inhibit tumor growth as an immunomodulator. However, its mechanism of action in immunosuppressive cells is unclear. The purpose of this study was to investigate whether TA can reshape the immune microenvironment by inhibiting the function of myeloid-derived suppressor cells (MDSCs) in non-small cell lung carcinoma (NSCLC). Methods: The effects of TA on peripheral blood monocytic MDSCs (M-MDSCs) in patients with NSCLC and on the apoptosis and migration of M-MDSCs were studied. A mouse subcutaneous xenograft tumor model was constructed, and the effect of TA on M-MDSC migration was evaluated. Quantitative real-time PCR, Western blotting, flow cytometry and immunohistochemistry were used to examine the mechanism by which TA affects M-MDSCs. Results: TA not only promoted the apoptosis of M-MDSCs by reducing the Bcl-2/BAX ratio but also and more importantly inhibited the migration of MDSCs to the tumor microenvironment by suppressing the production of vascular endothelial growth factor (VEGF) through the downregulation of hypoxia-inducible factor (HIF)-1α in tumor cells. Conclusions: TA may have a novel antitumor effect mediated by decreasing M-MDSC accumulation in the tumor microenvironment through reduced VEGF production.

The dysfunction of the intestinal epithelial barrier contributes to local or systemic infection and inflammation. Some lactic acid bacteria (LAB) strains had been shown to improve the conditions of barrier function and, for this reason, are recognized as probiotics. Weissella cibaria, a species belonging to the LAB group, is known to promote several health benefits. However, the role of W. cibaria in regulating the integrity of the intestinal epithelial barrier has not yet been investigated. In this study, W. cibaria MW01 was isolated from Chinese sauerkraut and was selected based on its functional features, such as gastric juice and bile salt tolerance, besides antagonistic activity against pathogenic bacteria. In a cellular model of the intestinal barrier, it was observed that W. cibaria was able to adhere more efficiently than Lactobacillus rhamnosus GG in Caco-2 cells. Moreover, the LPS-induced inflammation in Caco-2 cells was attenuated by the treatment with W. cibaria MW01, which reduced the synthesis of TNF-α, IL-6, and IL-8. In addition, it was noted that the treatment with W. cibaria MW01 recovered the integrity of the Caco-2 cell monolayer exposed to LPS. Furthermore, W. cibaria MW01 significantly alleviated LPS-induced downregulation of tight junction proteins (TJP) (claudin, occludin, and tight junction protein-1). Mechanistically, W. cibaria MW01 inhibited the translocation of NF-κB to the nucleus and deactivated the MLCK-pMLC pathway during LPS exposure. Thus, W. cibaria MW01, as a potential probiotic, can protect intestinal epithelial barrier function by regulating inflammation and expression of TJP via the NF-κB-mediated MLCK-pMLC pathway.

IntroductionMixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare form of neuroendocrine neoplasms (NENs). The purpose of this study was to investigate the characteristics and survival profile of appendiceal MiNENs, with a view of providing robust clinical features of this rare disease.MethodsPatients were selected from the Surveillance, Epidemiology, and End Results database (2004–2016). The prognosis of MiNEN (n = 315) was compared with other histological subtypes including neuroendocrine tumor (NETs) (n = 1734), neuroendocrine carcinoma (NECs) (n = 375), goblet cell carcinoid (GCC) (n = 968), signet ring cell carcinoma (n = 463), mucinous adenocarcinoma (MAC) (n = 2355), and non-mucinous adenocarcinoma (NMAC) (n = 1187) in the appendix. Age-adjusted incidence was calculated using Joinpoint regression. The Cox proportional hazards model and the Fine–Gray competing risk model were used to perform overall survival (OS) and cancer-specific mortality (CSM) analyses, respectively.ResultsThe age-adjusted incidence of MiNENs increased from 0.01/100,000 person-years in 2004 to 0.07/100,000 person-years in 2016. The 3-, 5-, and 10-year OS rates for MiNENs were 69.5, 57.4, and 43.7%, respectively, and the corresponding CSM rates were 23.1, 36.4, and 45.1%, respectively. Multivariate analysis revealed that the prognosis of MiNENs was worse than that of NETs, NECs, GCC, and MAC but better than that of NMAC and signet ring cell carcinoma. Tumor extension was the only independent factor influencing the prognosis of MiNENs, but tumor size, grade, and surgical approaches were not. Moreover, when compared with local excision or appendectomy, extensive surgery such as hemicolectomy or colectomy did not prolong the survival of individuals with MiNENs.ConclusionMiNEN is a rare but aggressive tumor with a poor prognosis differing from NENs, GCC and adenocarcinomas. To improve the prognosis of the disease, early diagnosis and comprehensive evaluation are necessary.

To study the effects of an axial magnetic field on the discharge characteristics of Ar inductively coupled plasma, a set of discharge plasma generators was designed. The plasma parameters such as electron temperature and electron density were diagnosed with a Langmuir probe. The research showed that as the air pressure was 10 Pa, with the increase in axial magnetic field intensity, the electron temperature and electron density reduced continuously in the central discharge region, while the threshold power of discharge mode transition increased constantly. The analysis suggested that due to the circumnutation of charged particles acted upon by Lorentz force, the introduction of the axial magnetic field had a constraint effect on the particle movement and energy transfer and decreased the collision between the high-energy electron in the discharge sheath and the electron in the central region, thereby reducing the electron density and inductive coupling efficiency. From further analysis of the electron energy probability function, it could be found that in the E mode, the constraint effect of the axial magnetic field on electron motion was more obvious. The proportion of the high-energy electron (>27 eV) was apparently higher than that in the H mode, and the electron energy distribution was more even. This was caused by less electron collision.

Abstract Background In recent years, outbreaks of varicella have continued to occur, and the coverage rate of varicella vaccine in Jiangsu Province, China, remains unclear. This study aims to analyse the levels of immune antibody against varicella and obtain a comprehensive understanding of the varicella attenuated live vaccine (VarV) coverage rate in children aged 1–9 years in Jiangsu Province. Methods From June to October 2016, a cross-sectional survey was conducted to collect 3631 serum samples from healthy children aged 1–9 years in Jiangsu Province. The immunoglobulin G (IgG) antibody levels of varicella were detected by enzyme-linked immunosorbent assay (ELISA). Results The VarV coverage rate of healthy children was only 43.1% (95% CI: 41.1–44.7%). The seroprevalence after vaccination with a single dose of VarV was only 57.1%, and the overall seropositivity and geometric antibody titre (GMC) were 43.5% and 225.4 mU/ml, respectively. The seropositivity was significantly higher in girls than in boys (χ2 = 18.82, P

Fatty liver disease: spent antioxidant and liver cell death An imbalance between ROS and antioxidant molecules, induced by a high-fat diet, is a major contributor to non-alcoholic fatty liver disease in a mouse model. Dr. Zhenyuan Song from the University of Illinois at Chicago, USA, and colleagues showed that a 12-week high-fat diet consumption led to increased expression of the pro-inflammatory signaling molecule TNFα in the liver. It also resulted in conversion of the antioxidant molecule glutathione (GSH) into a “spent” form called glutathione disulfide (GSSG), a sign that the liver has dealt with a lot of cellular stress. Experiments in human liver cells showed that intracellualr GSSG accumulation sensitizes hepatocytes to cell death via a molecular cascade triggered by TNFα activity. These findings point to GSSG as a potential drug target for treating non-alcoholic fatty liver disease.

Abstract Background A marked increase in the incidence rate of scarlet fever imposed a considerable burden on the health of children aged 5 to 15 years. The main purpose of this study was to depict the spatiotemporal epidemiological characteristics of scarlet fever in Jiangsu Province, China in order to develop and implement effective scientific prevention and control strategies. Methods Smoothed map was used to demonstrate the spatial distribution of scarlet fever in Jiangsu Province. In addition, a retrospective space-time analysis based on a discrete Poisson model was utilized to detect clusters of scarlet fever from 2005 to 2015. Results During the years 2005–2015, a total of 15,873 scarlet fever cases occurred in Jiangsu Province, with an average annual incidence rate of 1.87 per 100,000. A majority of the cases (83.67%) occurred in children aged 3 to 9 years. Each year, two seasonal incidence peaks were observed, the higher occurring between March and July, the lower between November and the following January. The incidence in the southern regions of the province was generally higher than that in the northern regions. Seven clusters, all of which occurred during incidence peaks, were detected via space-time scan statistical analysis. The most likely cluster and one of the secondary clusters were detected in the southern and northern high endemic regions, respectively. Conclusion The prevalence of scarlet fever in Jiangsu Province had a marked seasonality variation and was relatively endemic in some regions. Children aged 3 to 9 years were the major victims of this disease, and kindergartens and primary schools were the focus of surveillance and control. Targeted strategies and measures should be taken to reduce the incidence.

Splicing perturbation in cancers contribute to different aspects of cancer cell progression. However, the complete functional impact of cancer-associated splicing have not been fully characterized. Comprehensive large-scale studies are essential to unravel the dominant patterns of cancer-associated splicing. Here we analyzed the genome-wide splicing data in 16 cancer types with normal samples, identified differential splicing events in each cancer type. Then we took a network-based and modularized approach to reconstruct cancer-associated splicing networks, determine the module structures, and evaluate their prognosis relevance. This approach in total identified 51 splicing modules, among which 10/51 modules are related to patient survival, 8/51 are related to progression-free interval, and 5/51 are significant in both. Most of the 51 modules show significant enrichment of important biological functions, such as stem cell proliferation, cell cycle, cell growth, DNA repair, receptor or kinase signaling, and VEGF vessel development. Module-based clustering grouped cancer types according to their tissue-of-origins, consistent with previous pan-cancer studies based on integrative clustering. Interestingly, 13/51 modules are highly common across different cancer types, suggesting the existence of pan-cancer splicing perturbations. Together, modularized perturbation of splicing represents an functionally important and common mechanism across cancer types.

A new 3D cellular automata-lattice Boltzmann method (CA-LBM) coupling model is proposed to simulate the formation of facet and facet dendrites in directional solidification. In this model, the CA method is used to simulate the crystal growth process and the LBM method is used to simulate the physical field in the calculation area. A new three-dimensional anisotropic function is introduced, and the model is modified by interpolation and neighborhood restriction. We add the remelting calculation model. The interaction between interface energy anisotropy and dynamic anisotropy is solved reasonably. The growth process and morphology of small plane and small plane dendrites were simulated.

Pyridoxal kinase (PLK; EC 2.7.1.35) is a key enzyme in the metabolism of vitamin B6 (VB6) in Bombyx mori. A fusion expressional vector pET-22b-BPLK-His was constructed using a sub-cloning technique, the recombinant B. mori PLK was then expressed in Escherichia coli, purified and characterized. Bioinformatics were used to deduce the protein structure and genomic organization of this enzyme. Using Ni Sepharose affinity column chromatography, the recombinant protein was purified to very high degree (approximately 90%). The recombinant PLK exhibits a high specific enzymatic activity (1800 nmol/min/mg of protein). The maximum catalytic activity of this enzyme was recorded over a narrow pH range (5.5-6.0) and Zn2+ is the most effective cation for catalysis under saturating substrate concentrations. When only triethanolamine is present as the cation, K+ is an activator of PLK. A double reciprocal plot of initial velocity suggests that the enzyme catalyses the reaction by means of a sequential catalytic mechanism. Under optimal conditions, the Km value for the substrates of ATP and pyridoxal are 57.9 ± 5.1 and 44.1 ± 3.9 µM. B. mori's genome contains a single copy of the PLK gene, which is 7.73 kb long and contains five exons and four introns, and is located on the eighth chromosome. The PLK may be a dimer with two identical subunits under native conditions, and it is hypothesized that each monomer contains eight α-helices (α1-8), nine β-strands (β1-9) and two segments of 310 helices.

Silicon facet formation during directional solidification is simulated by cellular automaton (CA) modeling in which anisotropic interfacial energy and kinetics are considered. Numerical simulations were performed with different anisotropy strengths of interfacial energy and they show good agreement with analytical equilibrium shapes obtained by the Gibbs-Thomson equation. We also compare our results of anisotropic kinetics with in situ observation experiments and the results of the phase model to verify the accuracy of our model. Simulation results of facet formation show that perturbation is promoted to the corner by the negative temperature gradient of the interface and the heat accumulation location leads to the disappearance of small corners.

Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.