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This paper presents a novel control strategy for transferring large inertia loads using flexible space manipulators in orbit. The proposed strategy employs a Luenberger state observer and damping-stiffness controller to address issues of large tracking error and vibration. A comprehensive joint dynamics model is developed to identify the main sources of disturbance, and a Luenberger state observer is designed to estimate unmeasurable transmission deformation. Transmission stiffness and load inertia perturbations are identified based on the estimated results. By adjusting velocity damping and the gain of the forward channel, perturbations are suppressed to maintain optimal system damping and stiffness. Simulation and physical experiments demonstrate the effectiveness of the algorithm, with simulation experiments showing smoother joint output characteristics and minimal vibration under large load inertia changes, and a 97% reduction in internal deformation. Physical experiments demonstrate improved joint dynamic command tracking performance, with an 88% reduction in position tracking error. The algorithm provides a practical and efficient approach for transferring large inertia scientific payloads in space.

On-chip polarization control is in high demand for novel integrated photonic applications such as polarization division multiplexing and quantum communications. However, due to the sensitive scaling of the device dimension with wavelength and the visible-light absorption properties, traditional passive silicon photonic devices with asymmetric waveguide structures cannot achieve polarization control at visible wavelengths. In this paper, a new polarization-splitting mechanism based on energy distributions of the fundamental polarized modes in the r-TiO2 ridge waveguide is investigated. The bending loss for different bending radii and the optical coupling properties of the fundamental modes in different r-TiO2 ridge waveguide configurations are analyzed. In particular, a polarization splitter with a high extinction ratio operating at visible wavelengths based on directional couplers (DCs) in the r-TiO2 ridge waveguide is proposed. Polarization-selective filters based on micro-ring resonators (MRRs) with resonances of only TE or TM polarizations are designed and operated. Our results show that polarization-splitters for visible wavelengths with a high extinction ratio in DC or MRR configurations can be achieved with a simple r-TiO2 ridge waveguide structure.

A static experiment in greenhouse was conducted to investigate the growth of three grasses in high and medium eutrophic water and the effects of their removal on ammonia nitrogen (NH4+-N), nitrate nitrogen (NO3−-N), total nitrogen (TN), total phosphorus (TP), and the chemical oxygen demand (COD), and compared with cattail (Typha angustifolia). The results showed that 1) the removal efficiency of NH4+-N, NO3−-N, TN, TP, and COD treated by the four plants in eutrophic water were significantly higher than that in non-plant water. With the extension of treatment time, the concentrations of NH4+-N, NO3−-N, TN, TP, and COD in the eutrophic water decreased first and then tend to be stable. 2) Cynodon dactylon ‘Tifton 85’ (C. dactylon ‘Tifton 85’), Cortaderia selloana ‘Pumila’ (C. selloana ‘Pumila’) and T. angustifolia absorbed more than 95.7% and 88.6% of TN and TP in eutrophic water, and accumulate more than 89.5% and 82.0% in plants, respectively. However, the ratio of Cortaderia selloana ‘Silver Comet’ (C. selloana ‘Silver Comet’) was significantly lower. 3) The high abilities of these three plants to purify eutrophic water may be directly related to their rapid growth. 4) The comprehensive purification ability of the four plants to eutrophic was significantly different, in the order of C. dactylon ‘Tifton 85’ > C. selloana ‘Pumila’ ≈ T. angustifolia > C. selloana ‘Silver Comet’. These results indicated that C. dactylon ‘Tifton 85’ and C. selloana ‘Pumila’ can be used as alternative plants to T. angustifolia for the purification of eutrophic water. The results of this study can provide new materials and ideas for phytoremediation.

Abstract Owing to the immune microenvironment of bones and low selectivity of the drug, patients with bone metastases often respond poorly to immunotherapy. In this study, programmed cell death protein 1 (PD1)‐expressing hematopoietic stem cells (HSCs) are genetically engineered for bone‐targeted delivery of the transforming growth factor beta (TGF‐β) small‐molecule inhibitor SB‐505124 (SB@HSCs‐PD‐1). Intriguingly, compared to anti‐PD‐L1 monoclonal antibodies, as “living drugs”, HSCs‐PD‐1 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD‐1 molecules. The SB released from HSCs‐PD‐1 competitively bound to TGF‐β receptors on CD4+ T cells and facilitate CD4+ T cell differentiation to helper T (TH)1 and TH2 cells, thereby reprogramming the local immunosuppressive milieu of the bone marrow. Additionally, HSCs‐PD‐1 can block programmed death‐ligand 1 on tumor and myeloid cells, resulting in reinvigorated anti‐tumor immunity of T cells. In conclusion, in the present study, an alternative cell engineering strategy is delineated for immune checkpoint blockade therapy, to target bone metastasis using HSCs as a platform, which shows great promise in the treatment of bone metastases.

The mitochondrial unfolded protein response (UPRmt) is a molecular mechanism that maintains mitochondrial proteostasis under stress and is closely related to various metabolic diseases, such as type 2 diabetes (T2D). Similarly, the unfolded protein response of the endoplasmic reticulum (UPRER) is responsible for maintaining proteomic stability in the endoplasmic reticulum (ER). Since the mitochondria and endoplasmic reticulum are the primary centers of energy metabolism and protein synthesis in cells, respectively, a synergistic mechanism must exist between UPRmt and UPRER to cooperatively resist stresses such as hyperglycemia in T2D. Increasing evidence suggests that the protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) signaling pathway is likely an important node for coordinating UPRmt and UPRER. The PERK pathway is activated in both UPRmt and UPRER, and its downstream molecules perform important functions. In this review, we discuss the mechanisms of UPRmt, UPRER and their crosstalk in T2D.

Candida albicans is the most frequent pathogen of fungal sepsis associated with substantial mortality in critically ill patients and those who are immunocompromised. Identification of novel immune-based therapeutic targets from a better understanding of its molecular pathogenesis is required. Here, we reported that the production of progranulin (PGRN) levels was significantly increased in mice after invasive C.albicans infection. Mice that lacked PGRN exhibited attenuated kidney injury and increased survival upon a lethal systemic infection with C. albicans. In mice, PGRN deficiency protected against systemic candidiasis by decreasing aberrant inflammatory reactions that led to renal immune cell apoptosis and kidney injury, and by enhancing antifungal capacity of macrophages and neutrophils that limited fungal burden in the kidneys. PGRN in hematopoietic cell compartment was important for this effect. Moreover, anti-PGRN antibody treatment limited renal inflammation and fungal burden and prolonged survival after invasive C. albicans infection. In vitro, PGRN loss increased phagocytosis, phagosome formation, reactive oxygen species production, neutrophil extracellular traps release, and killing activity in macrophages or neutrophils. Mechanistic studies demonstrated that PGRN loss up-regulated Dectin-2 expression, and enhanced spleen tyrosine kinase phosphorylation and extracellular signal-regulated kinase activation in macrophages and neutrophils. In summary, we identified PGRN as a critical factor that contributes to the immunopathology of invasive C.albicans infection, suggesting that targeting PGRN might serve as a novel treatment for fungal infection.

ObjectiveSystemic inflammation is associated with a poor prognosis in acute heart failure (AHF). This study was to assess the long-term prognostic value of combining the accessible inflammatory markers in relation to all-cause mortality in patients with AHF.MethodsConsecutive patients with AHF who were hospitalized between March 2012 and April 2016 at the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University were enrolled in this prospective study. The LASSO regression model was used to select the most valuable inflammatory biomarkers to develop an inflammatory prognostic scoring (IPS) system. Kaplan-Meier method, multivariate COX regression and time-dependent ROC analysis were used to assess the relationship between inflammatory markers and AHF prognosis. A randomized survival forest model was used to estimate the relative importance of each inflammatory marker in the prognostic risks of AHF.ResultsA total of 538 patients with AHF were included in the analysis (mean age, 61.1 ± 16.0 years; 357 [66.4%] men). During a median follow-up of 34 months, there were 227 all-cause deaths (42.2%). C-reactive protein (CRP), red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) were incorporated into the IPS system (IPS = 0.301×CRP + 0.263×RDW + 0.091×NLR). A higher IPS meant a significantly worse long-term prognosis in Kaplan-Meier analysis, with 0.301 points as the optimal cut-off value (P log-rank

BackgroundAlthough most acute promyelocytic leukemia(APL) with low-intermediate risk could survive the induction treatment, early death still a big problem to have effects on overall survival in real world.This study aimed to analyze the clinical characteristics and possible predictors of early death in newly diagnosed patients with low-intermediate-risk acute promyelocytic leukemia.MethodsSixty patients with newly diagnosed low/intermediate-risk APL admitted to Mianyang Central Hospital from January 2013 to December 2021 were retrospectively analyzed.ResultsSixty patients with a median age of 46 years (range, 17-75 years) were included. Fourteen patients (23.3%) were in low-risk group, and 46 patients (76.7%) were in intermediate-risk group. Fourteen patients (23.3%) died during induction treatment. Five patients died of hemorrhage, 5 of severe infection and 4 of differentiation syndrome. Multivariate analysis showed that HGB

Summary: Organoids are considered a game-changing paradigm of research models for human physiology and disease, which provides unsurpassed opportunities across disciplines in basic medical research, drug development, and personalized medicine. Here, we made a deep investigation for global patents of organoid technologies in the past decade using bibliometric analysis for the first time. We have identified a total of 672 patents related to organoid technology. The number of annual patent applications exhibits an overall upward growth trend over the past decade, especially entering an exponential growth since 2015. Notably, 76.64% of patents are related to the construction of organoid models. Liver, brain, and intestinal models take up the first three places in the physiological models, while tumor models account for 76.30% of the total patents for disease models. Furthermore, drug screening is the most preferred application, revealing the great commercial value of organoid technologies in precision medicine and preclinical drug screening.

Plants dynamically manipulate their gene expression in acclimation to the challenging environment. Hereinto, the histone methylation tunes the gene transcription via modulation of the chromatin accessibility to transcription machinery. Osmotic stress, which is caused by water deprivation or high concentration of ions, can trigger remarkable changes in histone methylation landscape and genome-wide reprogramming of transcription. However, the dynamic regulation of genes, especially how stress-inducible genes are timely epi-regulated by histone methylation remains largely unclear. In this review, recent findings on the interaction between histone (de)methylation and osmotic stress were summarized, with emphasis on the effects on histone methylation profiles imposed by stress and how histone methylation works to optimize the performance of plants under stress.

Human pluripotent stem cell-derived liver organoids are emerging as more human-relevant in vitro models for studying liver diseases and hepatotoxicity than traditional hepatocyte cultures and animal models. The generation of liver organoids is based on the Matrigel dome method. However, the organoids constructed by this method display significant heterogeneity in their morphology, size, and maturity. Additionally, the formed organoid is randomly encapsulated in the Matrigel dome, which is not convenient for in situ staining and imaging. Here, we demonstrate an approach to generate a novel type of liver organoids via micropatterning technique. This approach enables the reproducible and high-throughput formation of bioengineered fetal liver organoids with uniform morphology and deterministic size and location in a multiwell plate. The liver organoids constructed by this technique closely recapitulate some critical features of human liver development at the fetal stage, including fetal liver-specific gene and protein expression, glycogen storage, lipid accumulation, and protein secretion. Additionally, the organoids allow whole-mount in-situ staining and imaging. Overall, this new type of liver organoids is compatible with the pharmaceutical industry’s widely-used preclinical drug discovery tools and will facilitate liver drug screening and hepatotoxic assessment.

BackgroundOwing to the coronavirus disease 2019 (COVID-19) pandemic and the emergency use of different types of COVID-19 vaccines, there is an urgent need to consider the effectiveness and persistence of different COVID-19 vaccines.MethodsWe investigated the immunogenicity of CoronaVac and Covilo, two inactivated vaccines against COVID-19 that each contain inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The levels of neutralizing antibodies to live SARS-CoV-2 and the inhibition rates of neutralizing antibodies to pseudovirus, as well as the immunoglobulin (Ig)G and IgM responses towards the spike (S) and nucleocapsid (N) protein of SARS-CoV-2 at 180 days after two-dose vaccination were detected.ResultsThe CoronaVac and Covilo vaccines induced similar antibody responses. Regarding neutralizing antibodies to live SARS-CoV-2, 77.9% of the CoronaVac vaccine recipients and 78.3% of the Covilo vaccine recipients (aged 18–59 years) seroconverted by 28 days after the second vaccine dose. Regarding SARS-CoV-2-specific antibodies, 97.1% of the CoronaVac vaccine recipients and 95.7% of the Covilo vaccine recipients seroconverted by 28 days after the second vaccine dose. The inhibition rates of neutralizing antibody against a pseudovirus of the SARS-CoV-2 Delta variant were significantly lower compared with those against a pseudovirus of wildtype SARS-CoV-2. Associated with participant characteristics and antibody levels, persons in the older age group and with basic disease, especially a chronic respiratory disease, tended to have lower anti-SARS-CoV-2 antibody seroconversion rates.ConclusionAntibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19 vaccines on SARS-CoV-2 variants.

The porous morphology and secondary phase originated from lithium evaporation have deteriorated dielectric properties of Li2Mg3SnO6 ceramic. To solve this issue, a set of non-stoichiometric Li2Mg3-2xSn1-xO6 (x = −0.04, −0.02, 0.00, 0.02, 0.04, 0.06) samples were prepared by the solid-state method. Subsequently, the effects of non-stoichiometry on the structural evolution, microstructure and dielectric properties of rock salt-type Li2Mg3-2xSn1-xO6 ceramics were investigated. The Rietveld refinement and SEM results confirmed that moderate non-stoichiometry could eliminate secondary phase and promote densification. For −0.04 ≤ x ≤ 0.04, the upward tendency of dielectric constant (εr) and quality factor (Q×f) was dominated by the improved phase purity and densification. As 0.04 ≤ x, the deterioration of dielectric characteristics was explained by the dielectric polarizability, lattice energy and packing fraction. The temperature coefficient of resonance frequency (τf) shifted from −36.41 to −27.23 ppm/°C, which could be attributed to the poor thermostability of Mg2SnO4 (τf = −64 ppm/°C) and enhanced octahedra bond energy.

The combination of histone deacetylase inhibitor and BRAF inhibitor (BRAFi) has been shown to enhance the antineoplastic effect and reduce the progress of BRAFi resistance. In this study, a series of (thiazol-5-yl)pyrimidin-2-yl)amino)-N-hydroxyalkanamide derivatives were designed and synthesized as novel dual inhibitors of BRAF and HDACs using a pharmacophore hybrid strategy. In particular, compound 14b possessed potent activities against BRAF, HDAC1, and HDAC6 enzymes. It potently suppressed the proliferation of HT-29 cells harboring BRAFV600E mutation as well as HCT116 cells with wild-type BRAF. The dual inhibition against BRAF and HDAC downstream proteins was validated in both cells. Collectively, the results support 14b as a promising lead molecule for further development and a useful tool for studying the effects of BRAF/HDAC dual inhibitors.

Podoplanin (PDPN) promotes platelet aggregation and activation by interacting with C-type lectin-like receptor 2(CLEC-2) on platelets. The interaction between the upregulated PDPN and platelet CLEC-2 stimulates venous thrombosis. PDPN was identified as a risk factor for coagulation and thrombosis in inflammatory processes. Hypercoagulability is defined as the tendency to develop thrombosis according to fibrinogen and/or D dimer levels. Nephrotic syndrome is also considered to be a hypercoagulable state. The aim of this study is to investigate the association of soluble PDPN/CLEC-2 with hypercoagulability in nephrotic syndrome. Thirty-five patients with nephrotic syndrome and twenty-seven healthy volunteers were enrolled. PDPN, CLEC-2 and GPVI concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome showed higher serum levels of PDPN and GPVI in comparison to healthy controls ( P 5.88 ng/ml, the risk of hypercoagulability was significantly increased in nephrotic syndrome (OR = 22.79, 95% CI 5.92-87.69, P

As the only overwintering oil crop in the north area of China, living through winter is the primary feature of winter rapeseed. Roots are the only survival organ during prolonged cold exposure during winter to guarantee flowering in spring. However, little is known about its root development and overwintering memory mechanism. In this study, root collar tissues (including the shoot apical meristem) of three winter rapeseed varieties with different cold resistance, i.e., Longyou-7 (strong cold tolerance), Tianyou-4 (middle cold tolerance), and Lenox (cold-sensitive), were sampled in the pre-winter period (S1), overwintering periods (S2–S5), and re-greening stage (S6), and were used to identify the root development and overwintering memory mechanisms and seek candidate overwintering memory genes by measuring root collar diameter and RNA sequencing. The results showed that the S1–S2 stages were the significant developmental stages of the roots as root collar diameter increased slowly in the S3–S5 stages, and the roots developed fast in the strong cold resistance variety than in the weak cold resistance variety. Subsequently, the RNA-seq analysis revealed that a total of 37,905, 45,102, and 39,276 differentially expressed genes (DEGs), compared to the S1 stage, were identified in Longyou-7, Tianyou-4, and Lenox, respectively. The function enrichment analysis showed that most of the DEGs are significantly involved in phenylpropanoid biosynthesis, plant hormone signal transduction, MAPK signaling pathway, starch and sucrose metabolism, photosynthesis, amino sugar and nucleotide sugar metabolism, and spliceosome, ribosome, proteasome, and protein processing in endoplasmic reticulum pathways. Furthermore, the phenylpropanoid biosynthesis and plant hormone signal transduction pathways were related to the difference in root development of the three varieties, DEGs involved in photosynthesis and carbohydrate metabolism processes may participate in overwintering memory of Longyou-7 and Tianyou-4, and the spliceosome pathway may contribute to the super winter resistance of Longyou-7. The transcription factor enrichment analysis showed that the WRKY family made up the majority in different stages and may play an important regulatory role in root development and overwintering memory. These results provide a comprehensive insight into winter rapeseed's complex overwintering memory mechanisms. The identified candidate overwintering memory genes may also serve as important genetic resources for breeding to further improve the cold resistance of winter rapeseed.

Bauhinia variegata petals are colorful, rich in anthocyanins, and have ornamental, nutritional, and medicinal value. However, the regulatory mechanism of anthocyanin accumulation in B. variegata remains unclear. In this study, a combined analysis of the metabolome and transcriptome was performed in red and white B. variegata cultivars in the early, middle, and blooming stages. A total of 46 different anthocyanins were identified, of which 27 showed marked differences in accumulation between the two cultivars, and contribute to their different petal colors. Malvidin 3-O-galactoside, peonidin 3-O-galactoside, cyanidin 3-O-glucoside, cyanidin 3-O-galactoside, and malvidin 3-O-glucoside were much more abundant in the second stage of flowering. In the blooming stage, except for the anthocyanins mentioned, delphinidin 3-O-galactoside and petunidin 3-O-galactoside were the most abundant anthocyanins in the red flowers, indicating that malvidin, peonidin, cyanidin, delphinidin, and petunidin were all responsible for the red color of petals in B. variegata. RNA sequencing identified 2,431 differentially expressed genes (DEGs), of which 26 were involved in the anthocyanin synthesis pathway. Correlations between the anthocyanin biosynthesis-related DEGs and anthocyanin contents were explored, and the DEGs involved in anthocyanin accumulation in B. variegata petals were identified. Eighteen of these DEGs encoded key catalytic enzymes, such as anthocyanidin reductase (ANR) and flavonoid-3′5′-hydroxylase (F3′5′H), and 17 of them encoded transcription factors (TFs) belonging to 14 families (including MYB, NAC, SPL, ERF, and CHR28). These results improve our understanding of the roles of anthocyanins, catalytic enzymes, and TFs in B. variegata petal-color expression.

Since the first report of SARS-CoV-2 virus in Wuhan, China in December 2019, a global outbreak of Corona Virus Disease 2019 (COVID-19) pandemic has been aroused. In the prevention of this disease, accurate diagnosis of COVID-19 is the center of the problem. However, due to the limitation of detection technology, the test results are impossible to be totally free from pseudo-positive or -negative. Improving the precision of the test results asks for the identification of more biomarkers for COVID-19. On the basis of the expression data of COVID-19 positive and negative samples, we first screened the feature genes through ReliefF, minimal-redundancy-maximum-relevancy, and Boruta_MCFS methods. Thereafter, 36 optimal feature genes were selected through incremental feature selection method based on the random forest classifier, and the enriched biological functions and signaling pathways were revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Also, protein-protein interaction network analysis was performed on these feature genes, and the enriched biological functions and signaling pathways of main submodules were analyzed. In addition, whether these 36 feature genes could effectively distinguish positive samples from the negative ones was verified by dimensionality reduction analysis. According to the results, we inferred that the 36 feature genes selected via Boruta_MCFS could be deemed as biomarkers in COVID-19.

Although peripheral venous blood biomarkers are related to respiratory function in Amyotrophic lateral sclerosis (ALS) patients, there are still few prediction models that predict pulmonary function. This study aimed to investigate the venous blood biomarkers associated with respiratory function in patients with ALS from southwest China and to create prediction models based on those clinical biomarkers using logistic regression. A total of 319 patients with ALS from the retrospective cohort and 97 patients with ALS from the prospective cohort were enrolled in this study. A multivariable prediction model for the correlation between peak expiratory flow (PEF) and hematologic, biochemical laboratory parameters, and clinical factors in patients with ALS was created. Along with female patients, bulbar-onset, lower body mass index (BMI), later age of onset, lower level of creatinine, uric acid, triglyceride, and a higher level of high-density lipoprotein cholesterol (HDL_C) were related to reduced PEF. The area under the receiver operating characteristics (ROC) curve is.802 for the test set and.775 for the validation set. The study constructed a multivariable prediction model for PEF in patients with ALS. The results can be helpful for clinical practice to predict respiratory impairment.

Abstract The mechanisms governing community assembly is fundamental to ecological restoration and clarification of the assembly processes associated with severe disturbances (characterized by no biological legacy and serious environmental problems) is essential. However, a systematic understanding of community assembly in the context of severe anthropogenic disturbance remains lacking. Here, we explored community assembly processes after metal mining, which is considered to be a highly destructive activity to provide insight into the assembly rules associated with severe anthropogenic disturbance. Using a chronosequence approach, we selected vegetation patches representing different successional stages and collected data on eight plant functional traits from each stage. The traits were classified as establishment and regenerative traits. Based on these traits, null models were constructed to identify the processes driving assembly at various successional stages. Comparison of our observations with the null models indicated that establishment and regenerative traits converged in the primary stage of succession. As succession progressed, establishment traits shifted to neutral assembly, whereas regeneration traits alternately converged and diverged. The observed establishment traits were equal to expected values, whereas regenerative traits diverged significantly after more than 20 years of succession. Furthermore, the available Cr content was linked strongly to species' ecological strategies. In the initial stages of vegetation succession in an abandoned metal mine, the plant community was mainly affected by the available metal content and dispersal limitation. It was probably further affected by strong interspecific interaction after the environmental conditions had improved, and stochastic processes became dominant during the stage with a successional age of more than 20 years.

Intestinal bacteria strains play crucial roles in maintaining host health. Researchers have increasingly recognized the importance of strain-level analysis in metagenomic studies. Many analysis tools and several cutting-edge sequencing techniques like single cell sequencing have been proposed to decipher strains in metagenomes. However, strain-level complexity is far from being well characterized up to date. As the indicator of strain-level complexity, metagenomic single-nucleotide polymorphisms (SNPs) have been utilized to disentangle conspecific strains. Lots of SNP-based tools have been developed to identify strains in metagenomes. However, the sufficient sequencing depth for SNP and strain-level analysis remains unclear. We conducted ultra-deep sequencing of the human gut microbiome and constructed an unbiased framework to perform reliable SNP analysis. SNP profiles of the human gut metagenome by ultra-deep sequencing were obtained. SNPs identified from conventional and ultra-deep sequencing data were thoroughly compared and the relationship between SNP identification and sequencing depth were investigated. The results show that the commonly used shallow-depth sequencing is incapable to support a systematic metagenomic SNP discovery. In contrast, ultra-deep sequencing could detect more functionally important SNPs, which leads to reliable downstream analyses and novel discoveries. We also constructed a machine learning model to provide guidance for researchers to determine the optimal sequencing depth for their projects (SNPsnp, https://github.com/labomics/SNPsnp). To conclude, the SNP profiles based on ultra-deep sequencing data extend current knowledge on metagenomics and highlights the importance of evaluating sequencing depth before starting SNP analysis. This study provides new ideas and references for future strain-level investigations.

Umbilical cord blood from singleton preterm infants was collected during delivery, and the concentration of LL37 was measured. C-reactive protein (CRP), white blood cell count (WBC), platelets (PLT), and mean platelet volume (MPV) were determined within 3 days after birth. The differences in LL37, CRP, WBC, PLT, and MPV levels between the two groups were compared. Pearson correlation method was used to analyze the correlation between these factors. The early individual value of each detected index for early onset sepsis was analyzed by ROC curve. The level of LL37 in umbilical cord blood of sepsis group was significantly higher than those in the control group (383.85 ± 46.71 vs. 252.37 ± 83.30 ng/ml). Meanwhile, the levels of CRP, WBC, and MPV in the sepsis group were significantly higher than those in the control group (CRP:5.73 ± 4.19 vs. 2.50 ± 2.77 mg/L; WBC: 13.47 ± 12.35 vs. 6.83 ± 3.55 × 109/L; MPV: 11.20 ± 1.11 vs. 8.90 ± 0.68 fL), the level of PLT was significantly lower than those in the control group (PLT: 161.00 ± 38.51 vs. 241.50 ± 49.85 × 109/L) (P < 0.05). Pearson correlation analysis showed that the expression of LL37 was negatively correlated with PLT level (r = −0.9347, P < 0.0001), and positively correlated with MPV level (r = 0.9463, P < 0.0001). ROC curve analysis showed that the area under curve of LL37 for diagnosis of early onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.

Moving object detection in remote sensing image sequences has been widely used in military and civilian fields. However, the complex background of remote sensing images and the small sizes of moving objects bring great difficulties for effective detection. To solve this problem, we propose a real-time moving object detection method for remote sensing image sequences. This method works by fusing the semantic information from a single image extracted by the object detection branch with the motion information of multiple frames extracted by the motion detection branch. Specifically, in the motion detection branch, we design a motion feature enhancement module (MFE) to improve the interframe motion information. Then, we design a Motion Information Extraction network (MIE) to extract motion information. Finally, the moving object information is directly output by fusing the motion and semantic information extracted by the object detection branch. Based on the experimental results of the two datasets, the proposed method achieves an accuracy rate of 93.21%, a recall rate of 92.72%, an average frame rate of 25.25 frames (fps), and a performance of 96.71% in terms of AP@0.5. The performance of the proposed method is better than that of other methods, and the overall detection effect is better; therefore, it meets the needs of the detection task.

The novel coronavirus pandemic is a major global public health emergency, and has presented new challenges and requirements for the timely response and operational stability of emergency logistics that were required to address the major public health events outbreak in China. Based on the problems of insufficient timeliness and high total system cost of emergency logistics distribution in major epidemic situations, this paper takes the minimum vehicle distribution travel cost, time cost, early/late punishment cost, and fixed cost of the vehicle as the target, the soft time window for receiving goods at each demand point, the rated load of the vehicle, the volume, maximum travel of the vehicle in a single delivery as constraints, and an emergency logistics vehicle routing problem optimization model for major epidemics was constructed. The convergence speed improvement strategy, particle search improvement strategy, and elite retention improvement strategy were introduced to improve the particle swarm optimization (PSO) algorithm for it to be suitable for solving global optimization problems. The simulation results prove that the improved PSO algorithm required to solve the emergency medical supplies logistics vehicle routing problem for the major emergency can reach optimal results. Compared with the basic PSO algorithm, the total cost was reduced by 20.09%.

In order to study the mechanical properties of ultra-high performance engineered cementitious composites (UHP-ECC) used for cable channel repair, orthogonal tests were carried out with four influencing factors, water binder ratio, silica fume, fly ash and mortar ratio, to obtain the optimum mix ratio of the cement paste. On this basis, the effects of ethylene-vinyl acetate (EVA) polymer and polyvinyl alcohol (PVA) fiber on the fluidity, flexural strength and compressive strength of UHP-ECC were studied, and the micromechanism was analyzed with SEM. The results show that the fluidity of UHP-ECC material prepared was 170–200 mm, which meets the requirements of working performance. The average compressive strength at 28 days reached 85.3 MPa, and the average flexural strength at 28 days reached 22.3 MPa. EVA polymer has a fast film forming rate in an alkaline environment. The formed polymer film wraps the fiber, enhances the bridging role between the fiber and the matrix and increases the viscosity of the material. Therefore, the early flexural strength is significantly improved. The 1-d flexural strength of UHP-ECC material mixed with 9-mm fiber is increased by 18%, and the 1-d flexural strength of 3-mm fiber is increased by 15%. Due to PVA fiber’s high elastic modulus and tensile strength, it improved the flexural and tensile properties of the material after incorporation, especially in the later stages; the 28-d flexural strength of UHP-ECC material mixed with 9-mm fiber increased by 12%, and the 28-d flexural strength of 3-mm fiber increased by 7%. It was concluded that the effect of 9-mm PVA fiber is better than that of 3 mm PVA fiber.

With the transformation and upgrading of the world economy entering a new normal, changes in the fields of industry and consumption have brought new business opportunities, and there is a large space for the less-than-truckload (LTL) express market. Considering the urban network resource operation status, this study aims to solve the optimization problem of urban location selection for LTL express under the common delivery model. To minimize the total cost of logistics and distribution, we established an integer programming model with constraints such as radiation range and service-capacity limitations. A model with a fixed reality-node strategy, an expanded initial antibody group strategy, improved traditional elite individual retention strategy and a node-clustering strategy was introduced. An improved immune optimization algorithm was further designed to obtain globally optimal solutions. With the comparison of existing algorithms, the results verified the practicability of the proposed model to solve the urban location-selection problems for LTL express. We then conducted an empirical analysis of a real-world enterprise’s reasonable urban network location selection in a central-south city of China. The simulation results further verified the effectiveness of our proposed algorithm. This study provides new solutions and methods for resource utilization and urban network optimization of LTL-express enterprises.

In the context of carbon neutralization, the electric vehicle and energy storage market is growing rapidly. As a result, battery recycling is an important work with the consideration of the advent of battery retirement and resource constraints, environmental factors, resource regional constraints, and price factors. Based on the theoretical research of intelligent algorithm and mathematical models, an integer programming model of urban power battery reverse supply chain scheduling was established with the goal of the highest customer satisfaction and the least total cost of logistics and distribution, to study the influence of the resources and operation status of a built city recycling center and dismantling center on the power battery reverse supply chain. The model includes vehicle load, customer demand point satisfaction range, and service capacity constraints. This study collected regional image data, conducted image analysis, and further designed an improved Non-dominated Sorting Genetic Algorithm-II (NSGA-II) optimization algorithm suitable to solve the global optimization problem by introducing the improvement strategy of convergence rate, particle search, and the traditional elite individual retention. The results verified the practicability of the model, the global optimization ability of the algorithm to solve the problem, and the operation speed through comparing the results obtained from the basic algorithm. A reasonable comprehensive solution for the location and path optimization of the urban recycling center was also obtained. Multi-objective optimization was carried out in vehicle scheduling, facility construction, and customer satisfaction construction. The basic algorithm and integrated optimization software were compared. We found that the model and the scheme provided by the algorithm can significantly reduce the operation cost of the enterprise. This research provided new insights for enterprises to effectively utilize resources and optimize the reverse supply chain scheduling of an urban power battery.

A biodegradable photodynamic antibacterial film (PS-CF) was prepared using the casting method, with κ-Carrageenan (κ-Car) as the film-forming substrate and curcumin-β-cyclodextrin (Cur-β-CD) complex as photosensitizer. Chilled pork samples were coated with PS-CF and stored at 4 °C to investigate the effects of PS-CF combined with LED light irradiation (425 nm, 45 min) (PS+L+) on pork preservation during 10 days of storage. The total viable count (TVC) of bacteria, total volatile basic nitrogen value (TVB-N) and the pH of pork treated with PS+L+ were all lower than the control, and the water-holding capacity (WHC) was higher. Ten days later, the TVB-N value was 12.35 ± 0.57 mg/100 g and the TVC value was 5.78 ± 0.17 log CFU/g, which was within the acceptable range. Sensory evaluation determined that the color, odor, and overall acceptability of pork treated with PS+L+ were significantly better than the control. These findings suggest that PS+L+ treatment effectively extended the shelf life of chilled pork from ~4–5 to 10 days. Correlation analysis showed that the sensory quality of the chilled pork significantly correlated with total bacterial counts, TVB-N and thiobarbituric acid reactive substances (TBARS) (p < 0.05), suggesting that these biomarkers could be used as standard indicators for evaluating the freshness of chilled pork. These findings demonstrate the effectiveness of Cur-β-CD photodynamic antibacterial film for the preservation of chilled pork and provide a theoretical basis for the application of the film for the preservation of fresh food in general.

Background: Androgens excess results in endoplasmic reticulum (ER) stress, which is an important cause of β cells dysfunction. Here, we investigated the molecular regulation of androgens excess, ER stress, and β-cell function in polycystic ovary syndrome (PCOS). Methods: PCOS mouse model was established by injection of DHEA. Primary cultured mouse islets were used to detect testosterone (TE)-induced ER stress. The response of ER stress, apoptosis, and hyperinsulinemia were analyzed in INS-1 cells with or without TE exposure. Androgen receptor (AR) antagonist and ER stress inhibitor treatment was performed to evaluate the role of TE in ER stress and proinsulin secretion of PCOS mice. Results: PCOS mice had higher ER stress in islets. TE exposure induced ER stress and apoptosis significantly through sustaining insulin overexpression in β cells, which in turn impaired proinsulin maturation and secretion. Blocking this pro cess could significantly relieve ER stress and apoptosis and improve insulin homeostasis. Conclusion: ER stress activated by androgens excess in PCOS contributes to β cell dysfunction and hyperinsulinemia.

Abstract The hormone renin plays a crucial role in the regulation of blood pressure and fluid-electrolyte homeostasis. Normally, renin is synthesized by juxtaglomerular (JG) cells, a specialized group of myoepithelial cells located near the entrance to the kidney glomeruli. In response to low blood pressure and/or a decrease in extracellular fluid volume (as it occurs during dehydration, hypotension, or septic shock) JG cells respond by releasing renin to the circulation to reestablish homeostasis. Interestingly, renin-expressing cells also exist outside of the kidney, where their function has remained a mystery. We discovered a unique type of renin-expressing B-1 lymphocyte that may have unrecognized roles in defending the organism against infections. These cells synthesize renin, entrap and phagocyte bacteria and control bacterial growth. The ability of renin-bearing lymphocytes to control infections—which is enhanced by the presence of renin—adds a novel, previously unsuspected dimension to the defense role of renin-expressing cells, linking the endocrine control of circulatory homeostasis with the immune control of infections to ensure survival.

Abstract Background Thoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks. Methods We analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm. Results We identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis. CX3CR1, C3, and C3AR1 were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells. Conclusion Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.

AbstractTo evaluate the stability of a prestressed railway embankment (PRE), approximate solutions for the additional normal and shear stresses on an arbitrary potential sliding surface of a PRE are first derived using the elastic theory, by which the propagation effect of additional stresses due to the prestressing loads is appropriately considered. Then, a limit equilibrium slice method incorporating the additional stress effect, equivalent interslice forces, track weight, and train axle load but avoiding repeated iteration calculations is developed to analyze the PRE stability. The additional stress solutions are also introduced to modify three commonly used conventional slope stability analysis methods, and comparative analyses were performed to investigate the applicability of the proposed method. The results showed that the differences between the safety factor (Fs) of a PRE evaluated using the proposed and modified methods were within 2% in this study and the values were less than those yielded by the conventional methods because of the partial negative effect of the additional normal and shear stresses on a few slices around the lateral pressure plate (LPP). Besides, the adaptive genetic algorithm was introduced to search the critical sliding surface of the PRE. Finally, the effect of reinforcement pressure on the stability of a PRE was investigated, where the results indicated that the Fs of the PRE increased from 1.323 to 1.626 with an increase of the reinforcement pressure from 0 to 200 kPa, while the PRE gradually varies from potential integral instability to potential local instability. The accurate and efficient determination of the additional stresses on the sliding surface is important in analyzing the PRE stability, and the developed method can provide an easy-to-use and relatively safer stability analysis method for the design of a PRE.

Osteoporosis, characterized by the destruction of bone resorption and bone formation, is a serious disease that endangers human health. Osteoporosis prevention and treatment has become one of the important research contents in the field of medicine. Acacetin, a natural flavonoid compound, could promote osteoblast differentiation, and inhibit osteoclast formation in vitro. However, the mechanisms of acacetin on osteoclast differentiation and type H vessel formation, as well as the effect of preventing bone loss, remain unclear. Here, we firstly used primary bone marrow derived macrophages (BMMs), endothelial progenitor cells (EPCs), and ovariectomized (OVX) mice to explore the function of acacetin on bone remodeling and H type vessel formation. In this study, we found that acacetin inhibits osteoclast formation and bone resorption of BMMs induced by the macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in a concentration of 20 μM without exerting cytotoxic effects. It was accompanied by downregulation of osteoclast differentiation marker genes (Ctsk, Acp5, and Mmp9) and cell fusion genes (CD9, CD47, Atp6v0d2, Dc-stamp, and Oc-stamp). Moreover, acacetin disrupted actin ring formation and extracellular acidification in osteoclasts. Mechanistic analysis revealed that acacetin not only inhibits the expression of the major transcription factor NFATc1 and NF-κB during RANKL-induced osteoclast formation, but also suppresses RANKL-induced the phosphorylation of Akt, GSK3β, IκBα, and p65. Additionally, acacetin enhanced the ability of M-CSF and RANKL-stimulated BMMs to promote angiogenesis and migration of EPCs. We further established that, in vivo, acacetin increased trabecular bone mass, decreased the number of osteoclasts, and showed more type H vessels in OVX mice. These data demonstrate that acacetin prevents OVX-induced bone loss in mice through inhibition of osteoclast function and promotion of type H vessel formation via Akt/GSK3β and NF-κB signalling pathway, suggesting that acacetin may be a novel therapeutic agent for the treatment of osteoporosis.

Self-lubricating aluminium-based composites reinforced with solid lubricants promise to meet the demand for lightweight materials in green tribological applications. The design advantages granted by additive manufacturing (AM) processes coupled with their capacity for in-situ production of composite materials are yet to be exploited in the realm of Al-transition metal dichalcogenides composites. In this work, laser powder bed fusion (LPBF) was deployed for the in-situ fabrication of Al-WS2 composites for the first time, elucidating the process-structure–property relationships in comparison to reference spark plasma sintering (SPS) samples. The WS2 response to the respective fabrication technique was also firstly investigated through a holistic characterisation. The formation of new phases (W for LPBF, Al5W and Al12W for SPS) provided the potential for microstructural tailoring for optimal tribological performance. For tribological properties, LPBF Al-WS2 exhibited a coefficient of friction (COF) 0.55 ± 0.01 and specific wear rate 3.4 ± 0.3 × 10−3 mm3/N∙m, slightly better than the SPS counterpart (COF 0.57 ± 0.02, specific wear rate 3.6 ± 0.3 × 10−3 mm3/N∙m). Furthermore, a novel methodology for studying the evolution of worn surfaces is proposed and validated, by which a tribo-layer formed at lower friction cycles was observed for the LPBF samples, meaning that AM will also be advantageous for the performance aspect of self-lubricating materials.

Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.

Kitchen fire has been becoming the majority risk to the ancient buildings, as the insufficient firefighting device, the excessive fuel, and the lower fire resistance structure. In this paper, a numerical simulation research was carried to access the effective of water spray in the kitchen fire of ancient buildings. The heat release rate (HRR), smoke temperature and spread process has been obtained, the efficiency of general water spray and kitchen special water spray has been compared, the necessary of the fire alarm device and the water spray have also discussed. The result indicated that the HRR peak is controlled by the water spray and fire detector devices, the activity time of water spray is the majority factor. The flame temperature is approximate to 400 °C without the firefighting device. Though the fire scenario protected by kitchen water spray and fire detector, the flame temperature is 67 °C and the HRR peak is 2.52 kW, which fire has been controlled in 32.7s. The result indicated that it is necessary for the ancient building's kitchen to fix the firefighting devices, and the numerical simulation is useful for the design and selection of firefighting device.

Intrauterine adhesions (IUAs) are important causes of female infertility, mainly but not always caused by iatrogenic endometrial injury. The microbiome of the female reproductive tract, including the vagina and uterine cavity, plays an important role in health and disease. Immune regulation imbalance caused by reproductive tract microecological disorders can act in the formation mechanism of IUAs. Here we collected clinical laboratory indicators, the vaginal secretions and uterine secretions of 6 women with and 8 women without IUAs, with a history of curettage. Vaginal and uterine cavity microbes were detected by high-throughput sequencing technology. Compared with the women without IUAs, the proportion of Lactobacillus in vaginal microbes was decreased and the proportion of Bacteroides was increased in the IUAs. The α-diversity index in the vaginal microbiome was significantly positively correlated with the hematocrit and erythrocyte count (P ＜0.05). These clinical and microbiological indicators could be used to indicate the occurrence of IUAs, so this study has clinical guiding significance for detecting and preventing them.

Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.

Considering that driving stress is a major contributor to traffic accidents, detecting drivers’ stress levels in time is helpful for ensuring driving safety. This paper attempts to investigate the ability of ultra-short-term (30-s, 1-min, 2-min, and 3-min) HRV analysis for driver stress detection under real driving circumstances. Specifically, the t-test was used to investigate whether there were significant differences in HRV features under different stress levels. Ultra-short-term HRV features were compared with the corresponding short-term (5-min) features during low-stress and high-stress phases by the Spearman rank correlation and Bland–Altman plots analysis. Furthermore, four different machine-learning classifiers, including a support vector machine (SVM), random forests (RFs), K-nearest neighbor (KNN), and Adaboost, were evaluated for stress detection. The results show that the HRV features extracted from ultra-short-term epochs were able to detect binary drivers’ stress levels accurately. In particular, although the capability of HRV features in detecting driver stress also varied between different ultra-short-term epochs, MeanNN, SDNN, NN20, and MeanHR were selected as valid surrogates of short-term features for driver stress detection across the different epochs. For drivers’ stress levels classification, the best performance was achieved with the SVM classifier, with an accuracy of 85.3% using 3-min HRV features. This study makes a contribution to building a robust and effective stress detection system using ultra-short-term HRV features under actual driving environments.

Castanopsis hystrix is a valuable native, broad-leaved, and fast-growing tree in South China. In this study, 15 phenotypic traits and 32 simple sequence repeat (SSR) markers were used to assess the genetic diversity and population structure of a natural population of C. hystrix and to construct a core germplasm collection by a set of 232 accessions. The results showed that the original population of C. hystrix had relatively high genetic diversity, with the number of alleles (Na), effective number of alleles (Ne), observed heterozygosity (Ho), expected heterozygosity (He), Shannon’s information index (I), and polymorphism information content (PIC) averaging at 26.188, 11.565, 0.863, 0.897, 2.660, and 0.889, respectively. Three sub-populations were identified based on a STRUCTURE analysis, indicating a strong genetic structure. The results from the phylogenetic and population structures showed a high level of agreement, with 232 germplasms being classified into three main groups. The analysis of molecular variance (AMOVA) test indicated that 96% of the total variance was derived from within populations, which revealed a low differentiation among populations. A core collection composed of 157 germplasms was firstly constructed thereafter, of which the diversity parameters non-significantly differed from the original population. These results revealed the genetic diversity and population structure of C. hystrix germplasms, which have implications for germplasm management and genome-wide association studies on C. hystrix, as well as for core collection establishment applications in other wood-producing hardwood species.

To overcome the low water solubility and low bioavailability of curcumin (CUR), multiple delivery strategies have been proposed. Among these, cyclodextrin-based carriers have been widely used for the encapsulation and delivery of CUR. Cyclodextrins (CDs), as natural oligosaccharides, have been well known for their biodegradability, biocompatibility, non-toxicity, and internal hydrophobic and external hydrophilic structural features. This paper summarizes the recently reported CD-based carriers for encapsulating CUR. Particularly, the polymerization properties of CD self-assembly to enhance the encapsulation of CUR are discussed. In addition, the current progress on stimuli-responsive CD carriers for controlled release of CUR is described, which laid an important foundation for the development of CUR-based precision therapy in clinical practice. In conclusion, this review may provide ideas for the future development of a CD-based encapsulant for CUR.

Polystyrene microplastics (PS MPs) are micrometer-scale items degraded from plastics and have been detected in various organisms. PS MPs have been identified as causing cognitive, cardiac, intestinal, and hepatic damage. However, their role in liver regeneration under drug-induced liver injury remains unknown. Thus, the current study aims to evaluate the impact of PS MPs on liver repair during APAP hepatotoxicity. PS MPs pretreatment exacerbates mice mortality and hepatocyte apoptosis, suppresses hepatic cell proliferation, and disturbs the inflammatory response in the APAP-induced damage model. Further mechanism exploration uncovers that prior PS MPs administration is sufficient to recruit neutrophils and macrophages, which are necessary for tissue recovery in the acute liver injury model. However, the polarization capacity of macrophages to anti-inflammatory sub-type is significantly delayed in PS MPs plus APAP group compared to the single APAP group, which is the leading cause of tissue repair suppression. Overall, the current study supports a new insight to realize the toxicity of PS MPs in acute liver injury, which should be considered in health risk assessment.

Zuczkowski et al.’s KUB model clarified three epistemic stances: Knowing/Certain, Not Knowing Whether and Believing/Uncertain, and Unknowing/Neither Certain nor Uncertain, according to the speakers’ communicated information, and delineated three types of markers: macro-markers, micro-markers, and morphosyntactic markers. The model has seldom been applied to L2 instruction. To address this gap, the study examines the effect of grade and genre-specific questions on Chinese L2 speakers’ choice of epistemic markers with reference to the model by analyzing the self-built corpus consisting of the oral data collected from two groups: Group One consisting of 20 sophomores and Group Two comprising 20 first-year graduate students. The participants were required to answer four genre-specific questions covering argumentation, description, narration, and exposition. The results show that the two group members use similar epistemic markers (EMs) for the Knowing/Certain and Not Knowing Whether and Believing /Uncertain positions but present a slight discrepancy in Unknowing/Neither Certain nor Uncertain stance-taking. The genre-based questions demonstrate a significant effect on the graduate speakers’ use of the micro-markers and morphosyntactic markers for the Not Knowing Whether and Believing/Uncertain and the macro-markers and morphosyntactic markers for the Unknowing/Neither Certain nor Uncertain. It indicates that high-grade speakers are more sensitive to genre-based messages, though they use rather limited epistemic forms as low-grade speakers do. The findings suggest that English as a Second Language (ESL) oral instruction in China should be reformed and supplemented with diverse EMs to allow the speakers to take the epistemic stance they are comfortable with.

The acidic tumor microenvironment (TME) is unfriendly to the activity and function of immune cells in the TME. Here, we report inorganic nanozymes (i.e., SnSe NSs) that mimic the catalytic activity of lactate dehydrogenase to degrade lactate to pyruvate, contributing to the metabolic treatment of tumors. As found in this study, SnSe NSs successfully decreased lactate levels in cells and tumors, as well as reduced tumor acidity. This is associated with activation of the immune response of T cells, thus alleviating the immunosuppressive environment of the TME. More importantly, the nanozyme successfully inhibited tumor growth in mutilate mouse tumor models. Thus, SnSe NSs show a promising result in lactate depletion and tumor suppression, which exemplifies its potential strategy in targeting lactate for metabolic therapy.

Abstract Background Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in regulating chemo-resistance of NSCLC, however, the role of lncRNA SNHG14 in the DDP-resistance of NSCLC remains unexplored. Methods Relative expression of SNHG14, HOXB13 and miR-133a in DDP-resistant A549 (A549/DDP) cell and its parental cell A549 were measured using qRT-PCR. Cell proliferation viability of indicated A549/DDP cell was estimated via CCK-8 and colony formation experiments. Cell cycle and apoptosis were analyzed through flow cytometry. Expression of apoptosis-related protein and HOXB13 were detected via western blot. The interaction among SNHG14, HOXB13 and miR-133a was predicted by bioinformatics and validated by dual-luciferase reporter assay. Results LncRNA SNHG14 and HOXB13 were upregulated while miR-133a was downregulated in A549/DDP cell line compared to A549 cell line. SNHG14 knockdown or miR-133a overexpression was demonstrated to increase the DDP-sensitivity of A549/DDP cells. SNHG14 was revealed to compete with HOXB13 for miR-133a binding in A549/DDP cells. Inhibition of miR-133a in A549 cells could reverse the promotive effects of SNHG14 knockdown on DDP-sensitivity, as well as the inhibitory effects on HOXB13 expression. HOXB13 overexpression was revealed to abolish the enhanced effects of miR-133a on the sensitivity of A549/DDP cell to DDP. Conclusion Our findings demonstrated that SNHG14 was involved in the development of DDP-resistance of A549/DDP cells through miR-133a/HOXB13 axis, which may present a path to novel therapeutic stratagems for DDP resistance of NSCLC.

Abstract Objective To investigate the effect of pathological staging of chorioamnionitis (CA) on complications in preterm infants; Methods A single-center, retrospective study was conducted to choose singleton preterm infants (gestational age

Chromosome and array comparative genomic hybridization (aCGH) analyses were performed on two cases of well-differentiated liposarcoma (WDLPS) and two cases of dedifferentiated liposarcoma (DDLPS). The results revealed the characteristic giant ring (GR) or giant rod marker (GRM) chromosomes in all four cases and amplification of numerous somatic copy number alterations (SCNAs) involving a core segment of 12q14.1q15 and other chromosomal regions in three cases. The levels of amplification for oncogenes OS9, CDK4, HMGA2, NUP107, MDM2, YEATS4, and FRS2 at the core segment or other SCNAs should be characterized to facilitate pathologic correlation and prognostic prediction. Further studies for the initial cellular crisis event affecting chromosome intermingling regions for cell-type specific gene regulation may reveal the underlying mutagenesis mechanism for GR and GRM in WDLPS and DDLPS.

Background Patients with inflammatory bowel disease (IBD) have higher health services use than those without IBD. We investigated patient and hospital characteristics of major ambulatory surgery encounters for Crohn’s disease (CD) or ulcerative colitis (UC) vs non-IBD patients. Methods We conducted a cross-sectional study using 2017 Nationwide Ambulatory Surgery Sample. Major ambulatory surgery encounters among patients aged ≥18 years with CD (n = 20,635) or UC (n = 9,894) were compared to 9.4 million encounters among non-IBD patients. Weighted percentages of patient characteristics (age, sex, median household income, primary payers, patient location, selected comorbidities, discharge destination, type of surgeries) and hospital-related characteristics (hospital size, ownership, location and teaching status, region) were compared by IBD status (CD, UC, and no IBD). Linear regression was used to estimate mean total charges, controlling for these characteristics. Results Compared with non-IBD patients, IBD patients were more likely to have private insurance, reside in urban areas and higher income zip codes, and undergo surgeries in hospitals that were private not-for-profit, urban teaching, and in the Northeast. Gastrointestinal surgeries were more common among IBD patients. Some comorbidities associated with increased risk of surgical complications were more prevalent among IBD patients. Total charges were 9% lower for CD patients aged Conclusions Differences in characteristics of major ambulatory surgery encounters by IBD status may identify opportunities for efficient resource allocation and positive surgical outcomes among IBD patients.