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Abstract Background Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms. Methods This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1β, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI. Results There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI). Conclusions LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque. Trial registration ChiCTR2200058529; Date of registration: 2022–04-10.

Honeycomb structures have been widely used in aerospace and automotive applications due to their high efficiency, high strength and high specific stiffness. However, most of the reported publications have focused on the surface shape variations of honeycomb structures, and there is a lack of studies on the variations of honeycomb structures with respect to the internal cell walls (Z-direction). To address these issues, this study proposes to combine the torsional design of honeycomb and Bouligand structures to fabricate twisted honeycomb structures (THS) with cell wall (z-direction) variations using powder bed fusion technology. The THS (30°) exhibits excellent specific energy absorption (SEA) performance, and the SEA of THS (0°), THS (60°), and THS (90°) are reduced by 8.5%, 19.7%, and 37.3%, respectively, compared with that of THS (30°) structure, and the THS (30°) has better repeatability. The effects of structural parameters on the energy absorption performance were analyzed. At THS (30°), changing the number of unit cells, wall length and wall thickness has a large effect on the compression performance. The results show that the specific energy absorption performance of THS reaches a maximum value of 74.6 kJ/kg for the number unit cells n = 3, wall length l = 5 mm and wall thickness t = 1 mm.

Abstract Myocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue damage. A significant aspect of this condition is reperfusion injury, which occurs when blood flow is restored but exacerbates the damage. This review first addresses the role of the innate immune system, including neutrophils and macrophages, in the cascade of events leading to myocardial infarction and reperfusion injury. It then shifts focus to the critical involvement of CD4+ T helper cells in these processes. These cells, pivotal in regulating the immune response and tissue recovery, include various subpopulations such as Th1, Th2, Th9, Th17, and Th22, each playing a unique role in the pathophysiology of myocardial infarction and reperfusion injury. These subpopulations contribute to the injury process through diverse mechanisms, with cytokines such as IFN-γ and IL-4 influencing the balance between tissue repair and injury exacerbation. Understanding the interplay between the innate immune system and CD4+ T helper cells, along with their cytokines, is crucial for developing targeted therapies to mitigate myocardial infarction and reperfusion injury, ultimately improving outcomes for cardiac patients.

The liver plays a crucrial role in detoxification, metabolism, and nutrient storage. Because liver cancer ranks among the top three leading causes of death globally, there is an urgent need for developing treatment strategies for liver cancer. Although traditional approaches such as radiation, chemotherapy, surgical removal, and transplantation are widely practiced, the number of patients with liver cancer continues to increase rapidly each year. Some novel therapeutics for liver cancer have been studied for many years. In the past decade, oncolytic therapy has emerged, in which viruses selectively infect and destroy cancer cells while sparing normal cells. However, oncolytic virotherapy for liver cancer remains relatively obscure due to the aggressive nature of the disease and the limited effectiveness of treatment. To keep pace with the latest developments in oncolytic tumor therapy for liver cancer, this review summarizes basic science studies and clinical trials conducted within 5 years, focusing on the efficacy and safety profiles of the five most commonly used oncolytic viruses: herpes simplex virus, adenovirus, influenza virus, vaccinia virus, and coxsackievirus.

Amubarvimab-romlusevimab is a commonly recommended antiviral treatment in China for adult patients with mild or moderate SARS-CoV-2 infections, especially for patients with a high risk factor for progression to severe COVID-19. However, its exact efficacy in patients with severe Covid-19 is not yet known.This is a single-center retrospective cohort study, in which we collected the general data, laboratory tests, radiological characteristics, viral conversion status, and prognosis of the disease from patients with COVID-19 hospitalized, from December 2022 to March 2023 in the Department of Critical Care Medicine. The amubarvimab-romlusevimab therapy can reduce the 28-day mortality (29.79 % vs 51.35 %, p = 0.02), and ICU mortality (29.79 % vs 55.41 %, p = 0.006) of severe COVID-19.A 1:1 PSM (Propensity Score Matching) was performed to reduce bias, in order to ensure the two groups were balanced and comparable. In the matched population (n = 47), there were no statistically significant differences between the mAbs (monoclonal antibody)group and the Non-antiviral group in 28-day, and thromboembolic events in COVID-19 patients. The 40-day survival analysis shows that mAbs therapy can improve patient prognosis (HR = 0.45, 95%CI = 0.26–0.76, p = 0.008). However, no significant intergroup difference in the 40-day cumulative viral conversion rate. In a univariate Cox regression analysis, The Amubarvimab - romlusevimab therapy(HR:0.464; CI:[0.252–0.853]; p:0.013) is a protective factor and CRP, PCT, PLT, Lactate, PT, PT-INR, and pt% level at admission were risk factors for clinical prognosis. After including the above covariates, Multifactorial COX regression shows that the Amubarvimab - romlusevimab therapy(HR:0.392; CI:[0.211–0.729]; p:0.003), CRP, Lactate and PT-INR at admission are independent factors for mortality of severe COVID-19. Based on the current data, we conclude that amubarvimab-romlusevimab therapy is beneficial for patients with severe COVID-19.

A novel three-dimensional (3D) printed hybrid continuous fiber reinforced bi-matrix composite is proposed in this paper to improve the flexural fracture energy and the designability of flexural mechanical properties, combining the excellent wettability of thermosetting resin to distinct fibers and the wonderful extrusion forming ability of thermoplastic for nozzle based additive manufacturing (AM). Numerical simulations are conducted by finite element (FE) and peridynamics (PD) models, enabling an in-depth study for the influence of printed hybrid configuration on flexural mechanical properties. The results show that assigning more basalt fibers at bottom effectively enhances the capability of flexural energy absorption, with the maximum enhancement of 126.1% in contrast to single-type carbon fiber reinforced samples. The combination of experimental analysis and numerical simulation has reference significance for structural optimization and failure prediction of hybrid continuous fiber composites printed by co-extrusion process.

The advantages of field-assisted laser additive manufacturing in optimizing microstructure and performance are increasingly recognized. Recently, we investigated the effects of acoustic field (AF) assisted laser powder bed fusion (LPBF) on the mechanical properties of 316L stainless steel (SS) and 316L SS/WC composite materials. Due to the effects of acoustic streaming and cavitation, acoustic field-assisted LPBF achieved optimized mechanical properties. Building on our previous research on AF-assisted LPBF, we introduced magnetic field (MF) and compound field (MF+AF) to study their effects on the microstructure and mechanical properties of 316L SS, 1 wt% and 3 wt% WC/316L SS. Application of the MF induces induced currents in the melt pool due to the Thomson-Seebek effect. The interaction between the MF and induced currents generates thermoelectric magnetic force (TEMF) and thermoelectric magnetic convection (TEMC), which inhibit the growth of columnar grains and enhance mass and heat transfer in the melt pool. Compound field-assisted LPBF reduced the dislocation density of 316L SS, refined grain size, alleviated the concentration distribution of grain orientation, and the ultimate tensile strength of the samples reached 777 MPa and the elongation at break reached 57.5%. Interestingly, for WC/316L SS, both MF and compound field resulted in a decrease in tensile performance, with ultimate tensile strengths as low as 677 MPa and elongations at break as low as 25.1%. This is because the MF affects the uniform distribution of WC particles, causing significant agglomeration and severe unmelted defects in the composite material, leading to a decrease in tensile performance.

A 60-day feeding trial was conducted to investigate the effects of dietary a Chinese herbal compound (CHC) including Pulsatillae Radix, Coptidis Rhizoma, Cortex Phellodendri Amurensis and Fraxini Cortex on the growth performance, intestinal and liver histology, antioxidative capacity and immunity of juvenile large yellow croaker (Larimichthys crocea) with the initial body weight of 17.00 ± 0.03 g. Four experimental diets were formulated to contain 0 mg/kg (CHC0), 250 mg/kg (CHC250), 500 mg/kg (CHC500), and 750 mg/kg (CHC750) of CHC, respectively. Results showed that dietary CHC did not significantly affect the survival of large yellow croaker (P > 0.05). Compared with the control, the CHC500 group showed higher weight gain and protein efficiency ratio, along with a lower feed conversion ratio (P < 0.05). Furthermore, increasing levels of dietary CHC linearly decreased the activities of aspartate aminotransferase and alanine aminotransferase, and malondialdehyde content in serum. Moreover, dietary CHC significantly increased the total antioxidative capacity and complement levels in serum (P < 0.05). The relative expressions of sod1, nrf2, il-10 and tnf-α in liver and intestine were upregulated in the CHC500 group (P < 0.05). Additionally, the activities of digestive and absorptive enzymes in intestine were significantly increased in the CHC500 group (P < 0.05). The length of intestinal villus height, villus width and perimeter ratio were higher in the CHC supplemented diets. In conclusion, CHC supplementation in diet could improve growth performance, anti-oxidative capacity and immunity of large yellow croaker.

The present study aims to investigate the effects of dietary Chinese herbs mixture (CHM) including Artemisia capillaris, Gardenia jasminoides, Scutellaria baicalensis, Reynoutria japonica and Uncaria rhynchophylla on the growth performance, anti-oxidative and immune responses, and intestine and liver histology of juvenile large yellow croaker Larimichthys crocea (initial body weight: 17.03 ± 0.03 g), which were fed graded levels of CHM (0 (control group), 250, 500 and 750 mg/kg, respectively) for 60 days. The results indicated that supplementing 250 and 500 mg/kg CHM in diet significantly increased the weight gain rate and decreased the feed conversion ratio of juvenile large yellow croaker (P < 0.05). The activities of lipase, chymotrypsin, γ-glutamyl transferase and Na+, K+-ATPase were significantly increased in CHM250 and/or CHM500 groups (P < 0.05). Besides, the levels of total anti-oxidative capacity, immunoglobulin M, complement 3 and complement 4 were significantly increased in the CHM250 and/or CHM500 groups (P < 0.05). The expressions of anti-oxidation gene (nuclear factor erythroid 2-related factor 2, nrf2), anti-inflammatory cytokines (interleukin-10, il-10 and transforming growth factor-β, tgf-β) and anti-apoptotic gene (B-cell lymphoma-2, bcl-2) in liver were significantly up-regulated, while the malondialdehyde content and the expressions of kelch like ECH associated protein 1 (keap1) and nuclear factor κB p65 (nf-κb p65) were significantly down-regulated after supplementing 250 and/or 500 mg/kg CHM in diet (P < 0.05). The histological analysis of liver and intestine showed the better morphology in CHM250 and CHM500 groups than the control group. In conclusion, above results indicated that dietary CHM (250 – 500 mg/kg) significantly improved the growth performance, anti-oxidative capacity, immunity and histology of liver and intestine of juvenile large yellow croaker.

The present study aimed to comparatively evaluate the protein requirements of large yellow croaker (initial body weight: 17.03 ± 0.11 g) fed with five dietary protein sources including fish meal (FM), cottonseed protein concentrate (CPC), Clostridium autoethanogenum protein (CAP), Tenebrio molitor meal (TM) and Chlorella meal (CM). The basal diet contained 30% of FM. Based on it, each of the five dietary protein sources was used to formulate graded levels of dietary protein (35%, 40%, 45%, 50%, 55% and 60%, respectively). After a 56-day feeding trial, it was indicated that the protein requirement of large yellow croaker was 50.91%, 44.95%, 39.92%, 40.34% and 52.19%, when FM, CPC, CAP, TM and CM were used as the dietary protein source, respectively. Overall, the TM and CM groups showed lower weight gain rat, feed intake, feed efficiency, protein efficiency ratio, protein retention and in vitro digestibility of dietary protein compared to the FM, CPC and CAP groups at the same dietary protein level. Meanwhile, the FM groups showed the highest amylase, lipase and trypsin activities followed by CPC, CAP, CM, and TM. At the same dietary protein level, the FM groups showed the highest muscularis thickness, villus height and perimeter ratio of intestine, followed by the CPC, CAP, CM and TM groups. The fish fed with dietary TM showed severe liver damage compared to those in the FM, CPC, CAP and CM groups. In summary, the present study demonstrated that the dietary protein requirement of large yellow croaker could be different because of different protein source included into diets. The CPC and CAP were more suitable as the alternative dietary protein sources for large yellow croaker than TM and CM according to the growth, feed utilization, digestive and absorptive enzyme activities, intestinal and liver histology analysis.

Owing to their great potential to enhance the structural, mechanical, and electrical properties of materials, numerous researchers have dedicated their efforts to manufacturing multi-walled carbon nanotubes (MWCNTs)-reinforced composites via additive manufacturing (AM) to leverage AM's ability to fabricate intricate structural components. However, there is currently limited research on MWCNTs in photosensitive resin (PR) systems processed via a type of vat photopolymerization AM technique - digital light processing (DLP). Additionally, the distribution pattern of MWCNTs in PR systems is still unknown. To address these research gaps, this investigation focuses on fabricating MWCNTs-reinforced PR (MWCNTs-PR) via DLP and studying the effects of MWCNTs content on microstructure characterizations and mechanical properties of MWCNTs-PR. These results show that PR with 0.05 wt% MWCNTs addition exhibits a 25 % increase in elastic modulus and a 2 % increase in bending strength compared to pure PR. To achieve a more uniform distribution of MWCNTs in the PR, a combination of an ultrasonic bath and mechanical stirring was adopted. To further investigate the mechanism behind MWCNTs-enhanced bending resistance, a multi-material layered 3D printing structure was developed. The experimental findings reveal that the 10001 structure yields the highest bending modulus, surpassing the control group by 14.9 %. To validate the bending resistance mechanism attributed to MWCNTs-PR, finite element analysis was conducted.

Due to its excellent corrosion and oxidation resistance, good formability, and affordability, 316L stainless steel (SS) is widely used in industries such as biomedical, marine, chemical, and water treatment. However, to further enhance its mechanical properties, scholars have turned to reinforcing 316L SS with ceramic additives. Among ceramic additives, tungsten carbide (WC) is favored due to its good wettability ability to bond closely with iron-based materials. Despite these benefits, defects of cracks, pores, and balling commonly exist in WC-reinforced metal matrix composites due to the agglomeration of WC particles. In response to these problems, author propose a novel method that combines acoustic field (AF) with powder bed fusion (PBF) to process WC-reinforced 316L SS materials. This approach takes advantages of AF's ability to homogenize materials, smooth out thermal gradient, reduce cracks, and refine grains in liquid materials, while also utilizing PBF's capabilities to fabricate complex-shaped customized parts with high density and good quality. Experimental results have shown that adding an AF to the PBF can reduce dislocation density, mitigate stress, alleviate cracks, refine grain size, and alter grain shape, ultimately enhancing the tensile properties of WC-reinforced 316L SS composites. By adopting this method, a balance of strength and ductility can be achieved, with ultimate tensile strength and percentage elongation falling into a narrow but high range of 750–930 MPa and 44–55%, respectively.

A continuous fiber reinforced two-matrix composites with multi-cavity structure was fabricated by a co-extrusion method, combining the excellent wettability of thermosetting resin to fiber and the wonderful extrusion forming ability of thermoplastic for nozzle based additive manufacturing (AM). Diversified component materials were utilized to enrich database for the AM of continuous fiber composites, including continuous carbon fiber (CCF), continuous basalt fiber (CBF), short fiber reinforced polyamide (SFRPA), polyamide (PA), polylactic acid (PLA) and epoxy resin. The tensile and flexural tests were conducted to investigate the effect of component materials on the mechanical properties. The micro-structures of printing filament and the fracture morphology of samples were characterized by optical microscope (OM) and scanning electron microscopy (SEM), respectively. A novel numerical model based on Peridynamics (PD) was proposed for the simulation of failure model. The three-dimensional (3D) printed continuous fiber reinforced two-matrix composites with multi-cavity structure show dissimilar mechanical behavior and failure characteristic for different combinations of component materials. The micro-structure of the fiber bundle pre-impregnated by epoxy resin after printing has a great influence on the mechanical properties and fracture modes of the samples. The failure modes mainly include pullout and breakage of fiber, stress whitening and crack of matrix, and interfacial debonding. The PD model effectively captures the tensile and flexural failure characteristic of 3D printed composites with multi-cavity structure. The results from experimental analysis and numerical simulation have reference significance for structural optimization and failure prediction of continuous fiber composites printed by co-extrusion process.

(1) Background: In-stent Restenosis (ISR) is a major factor influencing the prognosis and revascularization of target lesions. The plaque composition is unclear; therefore, it is critical to investigate ISR composition to identify clinical intervention markers. (2) Methods: This study was conducted on 36 patients with drug-eluting stent restenosis. The patients were classified into a Low Neutrophil–Lymphocyte Ratio (L-NLR) and High Neutrophil–Lymphocyte Ratio (H-NLR) according to the median NLR level of 36 patients. Discrepancies in the current information such as baseline data, biochemical examination, cardiac ultrasound data, etc., were examined to identify the underlying risk factors, and a multifactorial linear regression analysis of plaque properties was conducted. (3) Results: NLR = 2.64 was utilized to classify 18 patients into the L-NLR group and 18 patients into the H-NLR group. There were statistically significant differences in age, a pre-percutaneous coronary intervention (PCI) SYNTAX II score, a C-reactive protein (CRP), interleukin (IL)-6, plaque loading, a fibro-lipid tissue area, calcified nubs, and virtual histology-thin fibrous cap atherosclerotic (VH-TCFA). The significant impacts of variations in age, neutrophil–lymphocyte ratio (NLR) levels, and IL-6 levels on the plaque stress and percentage of the fibro-lipid tissue in virtual histology-intravascular ultrasound (VH-IVUS) were identified through multifactorial linear regression. (4) Conclusions: The high NLR group demonstrated increased myocardial injury severity, consistent with higher SYNTAX II scores, a higher plaque burden, and higher proportions of vulnerable components. NLR proved to be a risk factor for both the plaque load and the proportion of the fibro-lipid tissue in ISR.

Abstract Background Sepsis has a high mortality rate, which is expensive to treat, and is a major drain on healthcare resources; it seriously impacts the quality of human life. The clinical features of positive or non-positive blood cultures have been reported, but the clinical features of sepsis with different microbial infections and how they contribute to clinical outcomes have not been adequately described. Methods We extracted clinical data of septic patients with a single pathogen from the online Medical Information Mart for Intensive Care(MIMIC)-IV database. Based on microbial cultures, patients were classified into Gram-negative, Gram-positive, and fungal groups. Then, we analyzed the clinical characteristics of sepsis patients with Gram-negative, Gram-positive, and fungal infections. The primary outcome was 28-day mortality. The secondary outcomes were in-hospital mortality, the length of hospital stay, the length of ICU stay, and the ventilation duration. In addition, Kaplan–Meier analysis was used for the 28-day cumulative survival rate of patients with sepsis. Finally, we performed further univariate and multivariate regression analyses for 28-day mortality and created a nomogram for predicting 28-day mortality. Results The analysis showed that bloodstream infections showed a statistically significant difference in survival between Gram-positive and fungal organisms; drug resistance only reached statistical significance for Gram-positive bacteria. Through univariate and multivariate analysis, it was found that both the Gram-negative bacteria and fungi were independent risk factors for the short-term prognosis of sepsis patients. The multivariate regression model showed good discrimination, with a C-index of 0.788. We developed and validated a nomogram for the individualized prediction of 28-day mortality in patients with sepsis. Application of the nomogram still gave good calibration. Conclusions Organism type of infection is associated with mortality of sepsis, and early identification of the microbiological type of a patient with sepsis will provide an understanding of the patient's condition and guide treatment.

BackgroundAs a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression.MethodsWe recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison.ResultsSerum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R2 = 0.567, p

Poly-(ADP-ribose) polymerases (PARPs) are a protein family that make ADP-ribose modifications on target genes and proteins. PARP family members contribute to the pathogenesis of chronic inflammatory diseases, including atherosclerosis, in which monocytes/macrophages play important roles. PARP inhibition is protective against atherosclerosis. However, the mechanisms by which PARP inhibition exerts this beneficial effect are not well understood. Here we show that in THP-1 monocytes, inhibition of PARP by olaparib attenuated oxidized low-density lipoprotein (oxLDL)-induced protein expressions of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing-3 (NLRP3) inflammasome components: NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1. Consistent with this effect, olaparib decreased oxLDL-enhanced interleukin (IL)-1β and IL-18 protein expression. Olaparib also decreased the oxLDL-mediated increase in mitochondrial reactive oxygen species. Similar to the effects of the NLRP3 inhibitor, MCC950, olaparib attenuated oxLDL-induced adhesion of monocytes to cultured human umbilical vein endothelial cells and reduced foam cell formation. Furthermore, olaparib attenuated the oxLDL-mediated activation of nuclear factor (NF)-κB through the oxLDL-mediated increase in IκBα phosphorylation and assembly of NF-κB subunits, demonstrated by co-immunoprecipitation of IκBα with RelA/p50 and RelB/p52 subunits. Moreover, PARP inhibition decreased oxLDL-mediated protein expression of a NF-κB target gene, VCAM1, encoding vascular cell adhesion molecule-1. This finding indicates an important role for NF-κB activity in PARP-mediated activation of the NLRP3 inflammasome. Thus, PARP inhibition by olaparib attenuates NF-κB and NLRP3 inflammasome activities, lessening monocyte cell adhesion and macrophage foam cell formation. These inhibitory effects of olaparib on NLRP3 activity potentially protect against atherosclerosis.

In a powder bed fusion (PBF) process where powder bed preheating is needed, the powder bed will be subjected to an aging issue, which limits the reuse of powders. In response to the powder aging issue and to recycle powders, extensive attention has been attracted to study powder aging mechanisms in PBF to explore potential solutions. In this investigation, we have studied the aging mechanisms and proposed an epoxy resin solution (EP) infiltration method to mitigate side effects of powder aging in PBF-sintered nylon12 (PA12) specimens. Particularly, a comprehensive study on effects of powder recycling, building directions, and EP infiltration on microstructure characterizations, part quality, as well as thermal and mechanical properties of PBF-sintered PA12 specimens has been presented, for the first time. The quantitative relationships between sintering window width and warpage degree have been developed. A finite element analysis method has been utilized to learn stress distribution and concentration in PBF-sintered PA12 specimens and to predict fracture features. An insight into the strengthening effects induced by the EP infiltration at an atomic level has been provided by conducting molecular dynamic simulations.

Abstract Background Fragaria nilgerrensis, which is a diploid wild strawberry with excellent drought-resistance, would provide useful candidate genes for improving drought resistance of cultivated strawberry. So far, its molecular regulatory networks involved in drought stress are unclear. We therefore investigated the drought response regulatory networks of F. nilgerrensis based on the integrated analysis of DNA methylation, transcriptome and physiological traits during four time points under drought stress. Results The most differentially expressed genes and the physiological changes were found at 8 days (T8) compared with 0 day (T0, control). Methylome analysis revealed slight dynamic changes in genome-wide mC levels under drought conditions, while the most hypomethylated and hypermethylated regions were identified at T4 and T8. Association analysis of the methylome and transcriptome revealed that unexpressed genes exhibited expected hypermethylation levels in mCHG and mCHH contexts, and highly expressed genes exhibited corresponding hypomethylation levels in the gene body, but mCG contexts showed the opposite trend. Then, 835 differentially methylated and expressed genes were identified and grouped into four clustering patterns to characterize their functions. The genes with either negative or positive correlation between methylation and gene expression were mainly associated with kinases, Reactive Oxygen Species (ROS) synthesis, scavenging, and the abscisic acid (ABA) signal pathway. Consistently, weighted gene co-expression network analysis (WGCNA) revealed Hub genes including NCED, CYP707A2, PP2Cs and others that play important roles in the ABA signaling pathway. Conclusion F. nilgerrensis drought is dominated by ABA-dependent pathways, possibly accompanied by ABA-independent crosstalk. DNA methylation may affect gene expression, but their correlation was more subtle and multiple types of association exist. Maintaining the balance between ROS regeneration and scavenging is an important factor in drought resistance in F. nilgerrensis. These results deepen our understanding of drought resistance and its application in breeding in strawberry plants.

Material extrusion (ME) is considered as an effective and economic method to process continuous carbon fiber (CCF)-reinforced polymer composites with complicated structures. In this investigation, water absorption tests and tensile tests were conducted on ME-printed CCF-reinforced polymer composites under hydrothermal conditions. The purpose is to meet the growing need of CCF-reinforced polymer composites for high-humidity and high-heat aerospace applications. In order to achieve optimal comprehensive performance, both the L16 (45) orthogonal array method and the fuzzy reasoning algorithm were employed to carry out multi-objective optimization of four selected input variables, including layup angle, nozzle temperature, fiber filling density, and layer thickness. Experimental results show that the comprehensive performance of composites obtained by inputting data into the fuzzy reasoning system was greater than that obtained from orthogonal test results. Specifically, the optimized input variables are 0° layup angle, 260 °C nozzle temperature, 80% fiber filling rate, and 0.6 mm layer thickness.

ABSTRACT: Milk proteins have received much awareness due to their bioactivity. However, their encapsulation functions have not attracted enough attention. Milk proteins as encapsulation walls can increase the bioavailability of bioactive compounds. As the benefits of bioactive compounds are critically determined by bioavailability, the effect of interactions between milk proteins and active substances is a critical topic. In the present review, we summarize the effects of milk proteins as encapsulation walls on the bioavailability of active substances with a special focus. The methods and mechanisms of interactions between milk proteins and active substances are also discussed. The evidence collected in the present review suggests that when active substances are encapsulated by milk proteins, the bioavailability of active substances can be significantly affected. This review also provides valuable guidelines for the use of milk protein-based microcarriers.

Introduction and objectives: Thrombosis is involved in the onset and progression of ST-segment elevation myocardial infarction (STEMI). The aim of this study was to explore the expression level of serum- and glucocorticoid-inducible kinase 1 (SGK1) in intracoronary thrombus and the relationship between them. Methods: We identified 30 patients who received treatment in the Affiliated Hospital of Hangzhou Normal University between May 2018 to May 2020 and who underwent thrombus aspiration and percutaneous coronary intervention for ST-segment-elevation myocardial infarction. Additionally, we selected 30 patients with normal coronary angiography for the control group. We analyzed thrombus protein expression profiling by combining tandem mass tag labeling, high-performance liquid chromatography fractionation and mass spectrometry quantification approach. Results: The differentially regulated protein profiles revealed the alteration of serine-threonine/tyrosine-protein kinase, which was upregulated significantly in the experimental group. We selected SGK1 downstream factor for validation and found that the expression of SGK1 in the thrombus of STEMI was significantly increased. Immunohistochemistry (IHC) showed significantly increased expression of SGK1 in the thrombus of STEMI patients compared with the control group (17.21±2.36 vs. 4.14±1.17%, p

Abstract Pemphigus is an autoimmune skin disease. Ectopic lymphoid-like structures (ELSs) were found to be commonly present in the pemphigus lesions, presumably supporting in situ desmoglein (Dsg)-specific antibody production. Yet functional phenotypes and the regulators of Lymphoid aggregates in pemphigus lesions remain largely unknown. Herein, we used microarray technology to profile the gene expression in skin lesion infiltrating mononuclear cells (SIMC) from pemphigus patients. On top of that, we compared SIMC dataset to peripheral blood mononuclear cells (PBMC) dataset to characterize the unique role of SIMC. Functional enrichment results showed that mononuclear cells in skin lesions and peripheral blood both had over-represented IL-17 signaling pathways while neither was characterized by an activation of type I Interferon signaling pathways. Cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) results showed that naïve natural killer cells (NK cells) were significantly more abundant in pemphigus lesions, and their relative abundance positively correlated with B cells abundance. Meanwhile, plasma cells population highly correlated with type 1 macrophages (M1) abundance. In addition, we also identified a lncRNA LINC01588 which might epigenetically regulate T helper 17 cells (Th17)/regulatory T cells (Treg) balance via the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Here, we provide the first transcriptomic characterization of lesion infiltrating immune cells which illustrates a distinct interplay network between adaptive and innate immune cells. It helps discover new regulators of local immune response, which potentially will provide a novel path forward to further uncover pemphigus pathological mechanisms and develop targeted therapy.

In order to actively promote green production and address these concerns, there is an urgent need for new packaging materials to replace traditional plastic products. Starch−based packaging materials, composed of starch, fiber, and plasticizers, offer a degradable and environmentally friendly alternative. However, there are challenges related to the high crystallinity and poor compatibility between thermoplastic starch and fibers, resulting in decreased mechanical properties. To address these challenges, a novel approach combining plasticizer optimization and response surface method (RSM) optimization has been proposed to enhance the mechanical properties of starch−based packaging materials. This method leverages the advantages of composite plasticizers and process parameters. Scanning electron microscopy and X-ray crystallography results demonstrate that the composite plasticizer effectively disrupts the hydrogen bonding and granule morphology of starch, leading to a significant reduction in crystallinity. Fourier transform infrared spectroscopy results show that an addition of glycerol and D−fructose to the starch can form new hydrogen bonds between them, resulting in an enhanced plasticizing effect. The optimal process parameters are determined using the RSM, resulting in a forming temperature of 198 °C, a forming time of 5.4 min, and an AC content of 0.84 g. Compared with the non−optimized values, the tensile strength increases by 12.2% and the rebound rate increases by 8.1%.

BackgroundThe increasing rate of drug resistance often leads to Helicobacter pylori (H. pylori) eradication failure and needs the rescue therapy. Thus, the exploration of new rescue therapeutic regimens is important. The present study was designed to test the beneficial effects of Saccharomyces boulardii (S.boulardii) prior to H. pylori rescue therapy basing on bismuth quadruple.MethodsOne hundred H. pylori-infected patients were randomly divided into two groups: study group and control group. Patients in the study group (n=50) underwent two-stages therapy: patients started with S.boulardii monotherapy for 2 weeks, and then tested for H. pylori infection after resting for 4 weeks without any therapy, patients who were still positive for H. pylori continued with bismuth quadruple eradication therapy. For the control group (n=50), all patients were observed and were not treated with any gastric drugs or antibiotics for 6 weeks, then those who were still positive for H. pylori received the same eradication therapy as the study group. Eradication rate, adverse events and the cost-effectiveness of two regimens were analyzed in this study.ResultsThe H.pylori eradication rate of ITT (intent-to-treat) analysis and PP (per-protocol) analysis in the first phase of treatment were significantly higher in the study group than the control groups respectively (28.0% vs 2.0%, p

The Warburg effect is a promising target for the diagnosis and treatment of cancer, referring to the ability of cancer cells to generate energy through high levels of glycolysis even in the presence of oxygen, allowing them to grow and proliferate rapidly. The antipsychotic Pimozide has strong anti-breast cancer effects both in vivo and in vitro, whether Pimozide has an inhibitory effect on aerobic glycolysis has not been elucidated. In this study, Pimozide inhibited the Warburg effect of breast cancer cells by hindering glucose uptake, ATP level and lactate production; reducing the extracellular acidification rate (ECAR); suppressing the expression of PKM2, a rate-limiting enzyme in glycolysis. Intriguingly, Pimozide was significantly involved in reprogramming glucose metabolism in breast cancer cells through a p53-dependent manner. Mechanistic studies demonstrated Pimozide increased the expression of p53 through inhibition of the PI3K/Akt/MDM2 signaling pathway, which in turn downregulated the expression of PKM2. In sum, our results suggest that Pimozide mediates the p53 signaling pathway through PI3K/AKT/MDM2 to inhibit the Warburg effect and breast cancer growth, and it may be a potential aerobic glycolysis inhibitor for the treatment of breast cancer.

The present work aims to examine the effect of gelatin on the stabilization of silver nanoparticles (AgNPs) and their use in healing the bone fracture. AgNPs-loaded Gel hydrogels (AgNPs/Gel) were fabricated under sunlight using gelatin (Gel) as stabilizing agent. The characterization of the synthesized hydrogels was performed with the help of techniques such as UV-visible spectroscopy (UV-Vis) and high-resolution transmission electron microscopy (HR-TEM). Furthermore, the results of cell cytotoxicity confirmed that the AgNPs/Gel hydrogels are nonhazardous to osteoblasts. The outcome of cell fixation with AgNPs/Gel hydrogels after an incubation period of five days exposed the improved survival and spreading of osteoblasts cells on the prepared AgNPs/Gel hydrogels. Moreover, the AgNPs/Gel hydrogel nanostructures displayed their ability in modulating bone fracture healing, which suggests their potential use in nursing care.

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells derived from bone marrow that play critical immunosuppressive functions in the tumor microenvironment (TME), promoting cancer progression. According to base length, Non-coding RNAs (ncRNAs) are mainly divided into: microRNAs (miRNAs), lncRNAs, snRNAs and CircRNAs. Both miRNA and lncRNA are transcribed by RNA polymerase II, and they play an important role in gene expression under both physiological and pathological conditions. The increasing data have shown that MiRNAs/LncRNAs regulate MDSCs within TME, becoming one of potential breakthrough points at the investigation and treatment of cancer. Therefore, we summarize how miRNAs/lncRNAs mediate the differentiation, expansion and immunosuppressive function of tumor MDSCs in TME. We will then focus on the regulatory mechanisms of exosomal MicroRNAs/LncRNAs on tumor MDSCs. Finally, we will discuss how the interaction of miRNAs/lncRNAs modulates tumor MDSCs.

Abstract Chronic kidney disease (CKD) is characterized by inflammation, injury and fibrosis. Dysregulated innate immune responses mediated by macrophages play critical roles in progressive renal injury. The differentiation and polarization of macrophages into pro-inflammatory ‘M1’ and anti-inflammatory ‘M2’ states represent the two extreme maturation programs of macrophages during tissue injury. However, the effects of macrophage polarization on the pathogenesis of CKD are not fully understood. In this review, we discuss the innate immune mechanisms underlying macrophage polarization and the role of macrophage polarization in the initiation, progression, resolution and recurrence of CKD. Macrophage activation and polarization are initiated through recognition of conserved endogenous and exogenous molecular motifs by pattern recognition receptors, chiefly, Toll-like receptors (TLRs), which are located on the cell surface and in endosomes, and NLR inflammasomes, which are positioned in the cytosol. Recent data suggest that genetic variants of the innate immune molecule apolipoprotein L1 (APOL1) that are associated with increased CKD prevalence in people of African descent, mediate an atypical M1 macrophage polarization. Manipulation of macrophage polarization may offer novel strategies to address dysregulated immunometabolism and may provide a complementary approach along with current podocentric treatment for glomerular diseases.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) exhibit the capacity to self-renew and differentiate into multi-lineage cell types, including osteoblasts, which are crucial regulators of fracture healing. Thus, this study aims to investigate the effect of microRNA (miR)-22-3p from BMSC-derived EVs on osteogenic differentiation and its underlying mechanism. Methods Extracellular vesicles (EVs) were isolated from BMSCs and taken up with BMSCs. Dual-luciferase reporter gene assay was used to verify the binding relationship between miR-22-3p and FTO. Loss- and gain-of-function experiments were performed to determine the roles of EV-delivered miR-22-3p and FTO in osteogenic differentiation as well as their regulatory role in the MYC/PI3K/AKT axis. To determine the osteogenic differentiation, ALP and ARS stainings were conducted, and the levels of RUNX2, OCN, and OPN level were determined. In vivo experiment was conducted to determine the function of EV-delivered miR-22-3p and FTO in osteogenic differentiation, followed by ALP and ARS staining. Results miR-22-3p expression was repressed, while FTO expression was elevated in the ovariectomized mouse model. Overexpression of miR-22-3p, EV-delivered miR-22-3p, increased ALP activity and matrix mineralization of BMSCs and promoted RUNX2, OCN, and OPN expressions in BMSCs. miR-22-3p negatively targeted FTO expression. FTO silencing rescued the suppressed osteogenic differentiation by EV-delivered miR-22-3p inhibitor. FTO repression inactivated the MYC/PI3K/AKT pathway, thereby enhancing osteogenic differentiation both in vivo and in vitro. Conclusion In summary, miR-22-3p delivered by BMSC-derived EVs could result in the inhibition of the MYC/PI3K/AKT pathway, thereby promoting osteogenic differentiation via FTO repression.

The forest–medicinal plant management system has benefited the commercial production of Amomum villosum. However, little is known about the influence of different forestlands on the cultivation of A. villosum. The present study investigated the potential differences in the A. villosum yield and quality parameters, rhizosphere soil properties, and rhizosphere soil microbiota between a rubber plantation (RP) and a natural secondary forest (NSF). No significant differences in yield or rhizosphere soil properties of A. villosum were observed between RP and NSF, although most of the A. villosum yield parameters, the rhizosphere soil physicochemical properties, and soil enzyme activities were higher in NSF than in RP. Furthermore, the 38 volatile components had significantly higher relative abundances in NSF than in RP. Furthermore, the alpha diversity indices for the microbiota communities in the A. villosum rhizosphere soil indicated that the richness of the bacterial and fungal communities was significantly higher in NSF than in RP. These findings suggest that NSF conditions may be more appropriate than RP conditions for growing A. villosum. The data generated in this study may be useful for increasing the production of high-quality A. villosum via the exploitation of natural environments.

Coffee is one of the most valuable agricultural commodities worldwide, second only to oil in terms of international trade. Coffea arabica L. is a widely cultivated and economically important crop that is responsible for about 90% of the global production of coffee. In this study, we selected five C. arabica cultivation sites at different altitudes to clarify the effects of altitude on rhizospheric soil physical–chemical characteristics and microbial communities. The samples collected at low altitudes were more nutrient-deficient and acidic than the soil samples collected at medium–high altitudes. The Proteobacteria-to-Acidobacteria ratio increased from lower altitudes to medium–high altitudes. Additionally, although Ascomycota was the dominant fungal phylum, it was unaffected by the altitude. Furthermore, the alpha richness and diversity of the bacterial and fungal communities were higher at medium–high altitudes than at low altitudes. Moreover, the redundancy analysis indicated that microbial phyla were closely associated with pH. These findings suggest that C. arabica should be cultivated at medium–high altitudes, which is conducive to sustainable management and the production of high-quality C. arabica beans.

Abstract Background Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. Methods We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. Results A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28–2.57, p

Amomum villosum, which is an important perennial medicinal plant, easily suffers from continuous cropping obstacles in the plantation. The aim of this study is to find an effective method to solve the problem of A. villosum continuous cropping. In this study, we analyzed four fields in which A. villosum was continuously cropped and a fallow field to reveal the effects of continuous cropping on the rhizosphere soil physicochemical properties, enzyme activities, and bacterial and fungal communities. Most of the soil nutrient contents gradually increased as the number of years of continuous cropping increased, whereas the soil pH decreased slightly. The soil urease and acid phosphatase activities tended to increase as the length of the continuous cropping period increased, which may have accelerated the conversion of soil substances. Furthermore, the alpha diversity of the bacterial and fungal communities decreased as the duration of the continuous cropping period increased. Additionally, the redundancy analysis revealed that bacterial and fungal community structures at the phylum level were the most correlated with pH value and catalase activity, respectively. This study may be useful for promoting the continuous cropping and sustainable development of A. villosum.

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

The tumor microenvironment (TME) is composed of tumor cells, blood/lymphatic vessels, the tumor stroma, and tumor-infiltrating myeloid precursors (TIMPs) as a sophisticated pathological system to provide the survival environment for tumor cells and facilitate tumor metastasis. In TME, TIMPs, mainly including tumor-associated macrophage (TAM), tumor-associated dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs), play important roles in repressing the antitumor activity of T cell or other immune cells. Therefore, targeting those cells would be one novel efficient method to retard cancer progression. Numerous studies have shown that traditional Chinese medicine (TCM) has made extensive research in tumor immunotherapy. In the review, we demonstrate that Chinese herbal medicine (CHM) and its components induce tumor cell apoptosis, directly inhibiting tumor growth and invasion. Further, we discuss that TCM regulates TME to promote effective antitumor immune response, downregulates the numbers and function of TAMs/MDSCs, and enhances the antigen presentation ability of mature DCs. We also review the therapeutic effects of TCM herbs and their ingredients on TIMPs in TME and systemically analyze the regulatory mechanisms of TCM on those cells to have a deeper understanding of TCM in tumor immunotherapy. Those investigations on TCM may provide novel ideas for cancer treatment.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate in tumor-bearing hosts to reduce T cells activity and promote tumor immune escape in the tumor microenvironment (TME). The immune system in the TME can be stimulated to elicit an anti-tumor immune response through immunotherapy. The main theory of immunotherapy resides on the plasticity of the immune system and its capacity to be re-educated into a potent anti-tumor response. Thus, MDSCs within the TME became one of the major targets to improve the efficacy of tumor immunotherapy, and therapeutic strategies for tumor MDSCs were developed in the last few years. In the article, we analyzed the function of tumor MDSCs and the regulatory mechanisms of agents targeting MDSCs in tumor immunotherapy, and reviewed their therapeutic effects in MDSCs within the TME. Those data focused on discussing how to promote the differentiation and maturation of MDSCs, reduce the accumulation and expansion of MDSCs, and inhibit the function, migration and recruitment of MDSCs, further preventing the growth, invasion and metastasis of tumor. Those investigations may provide new directions for cancer therapy.

ObjectiveMesenchymal stem cells (MSCs) confer therapeutic benefits in various pathologies and cancers by releasing extracellular vesicles (EVs) loaded with bioactive compounds. Herein, we identified bone marrow MSC (BMSC)-derived EVs harboring microRNA (miR)-29b-3p to regulate osteogenic differentiation through effects on the suppressor of cytokine signaling 1 (SOCS1)/nuclear factor (NF)-κB pathway via targeting of lysine demethylase 5A (KDM5A) in osteoporosis.MethodsWe quantified the miR-29b-3p in BMSC-derived EVs from bone marrow specimens of osteoporotic patients and non-osteoporotic patients during total hip arthroplasty (THA). miR-29b-3p targeting KDM5A was confirmed by promoter luciferase assay, and enrichment of KDM5A in the promoter region of SOCS1 was analyzed by chromatin immunoprecipitation (ChIP). The expression and translocation of NF-κB to the nucleus were detected by western blot analysis and immunofluorescence staining, respectively. An ovariectomized (OVX) osteoporosis mouse model was established to further confirm the in vitro findings.ResultsBMSC-derived EVs of osteoporotic patients exhibited downregulated miR-29b-3p. EV-encapsulated miR-29b-3p from BMSCs potentiated osteogenic differentiation by specifically inhibiting KDM5A. KDM5A inhibited osteogenic differentiation by the regulation of H3K4me3 and H3K27ac of SOCS1. SOCS1 potentiated osteogenic differentiation by inhibiting NF-κB pathway.ConclusionEV-encapsulated miR-29b-3p derived from BMSCs potentiated osteogenic differentiation through blockade of the SOCS1/NF-κB pathway by inhibition of KDM5A.

Antibiotic resistance is becoming significantly prominent and urgent in clinical practice with the increasing and wide application of antibacterial drugs. However, developing and synthesizing new antimicrobial drugs is costly and time-consuming. Recently, researchers shifted their sights to traditional Chinese medicine (TCM). Here, we summarized the inhibitory mechanism of TCM herbs and their active ingredients on bacteria, discussed the regulatory mechanism of TCM on antibiotic-resistant bacteria, and revealed preclinical results of TCM herbs and their active components against antibiotic-resistant bacteria in mouse models. Those data suggest that TCM herbs and their effective constituents exhibit potential blockage ability on antibiotic-resistant bacteria, providing novel therapeutic ideas for reversing antibiotic resistance.

Andrographis paniculata (Chinese name: Chuanxinlian) is an annual dicotyledonous medicinal plant widely grown in China and Southeast Asia. The dried plant has a highly acclaimed usage in the traditional Chinese medicine for its antipyretic, anti-inflammatory, and analgesic effects. In order to help delineate the biosynthetic pathways of various secondary metabolites, we report in this study a high-quality reference genome for A. paniculata. With the help of both PacBio single molecule real time sequencing and Illumina sequencing reads for error correction, the A. paniculata genome was assembled into a total size of 284 Mb with a contig N50 size of 5.14 Mb. The contigs were further assembled into 24 pseudo-chromosomes by the Hi-C technique. We also analyzed the gene families (e.g., KSL, and CYP450) whose protein products are essential for synthesizing bioactive compounds in A. paniculata. In conclusion, the high-quality A. paniculata genome assembly builds the foundation for decoding the biosynthetic pathways of various medicinal compounds.

Introduction The habenular nucleus (Hb), a famous relay station in the midbrain, is vital for controlling many physiological functions of vertebrates. The role of Hb in the pathogenesis of depression has been thoroughly studied, but whether it functions in the pathogenesis of diabetes remains unknown. In this study, we found that Hb lesions could improve glucose metabolism in type 2 diabetes mellitus (T2DM) by inhibiting the peripheral sympathetic nervous system and hepatic glucose production.Research design and methods T2DM rats were induced by a high-carbohydrate and fat diet combined with streptozotocin. Electrical lesion method was applied to suppress the function of Hb. Serum and tissue samples of rats in the control group, T2DM group, sham group, and Hb lesion group were detected by ELISA, western blotting, and biochemical methods.Results Compared with the sham group, the expression levels of AMPK phosphorylation and insulin receptor (IR) were significantly increased, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxylated kinase were reduced in the liver of the Hb lesion group. In the glucose tolerance test and pyruvate tolerance test, the lesion group showed stronger glucose tolerance and lower hepatic gluconeogenesis than the sham. These results suggest that Hb lesions not only effectively increase insulin sensitivity and improve insulin resistance but also inhibit gluconeogenesis in T2DM rats. Moreover, Hb lesions increase the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, glucocorticoid receptor, and IR in the hippocampus. In this study, we also found that Hb lesions increase the content of acetylcholine in the adrenal glands and reduce the content of epinephrine in both the adrenal glands and the liver, which may be the main reason for the Hb lesions to regulate glucose metabolism in the liver.Conclusion Hb is an important neuroanatomical target for the regulation of glucose metabolism in the central nervous system of diabetic rats.

Antimicrobial peptides (AMPs) are small proteins with broad-spectrum antimicrobial activities, and could kill a variety of pathogens. In this study, 50 mg/kg (G1 group), 100 mg/kg (G2), and 200 mg/kg (G3) of AMPs were added to the basal diet (0 mg/kg AMPs, G0 group) of the largemouth bass (Micropterus salmoides). After feeding for 60 days, the growth performance, muscle composition, the activities of antioxidase immune-related enzymes and digestive enzymes, and intestinal morphology of M. salmoides were measured. The results showed that the final weight, weight gain rate, and specific growth rate were significantly higher in the G3 group than in the control group (G0) (p < 0.05). The crude protein of muscle in G3 group was significantly higher than in G0 group (p

Ginsenosides, the key components isolated from ginseng, have been extensively studied in antitumor treatment. Numerous studies have shown that ginsenosides have direct function in tumor cells through the induction of cancer cell apoptosis and the inhibition of cancer cell growth and enhance the antitumor immunity through the activation of cytotoxic T lymphocytes and natural killer cells. However, little is known about the function of ginsenosides on myeloid immunosuppressive cells including dendritic cells in tumor, tumor-associated macrophages, and myeloid-derived suppressor cells in the tumor microenvironments. Those myeloid immunosuppressive cells play important roles in promoting tumor angiogenesis, invasion, and metastasis. In the review, we summarize the regulatory functions of ginsenosides on myeloid immunosuppressive cells in tumor microenvironment, providing the novel therapeutic methods for clinical cancer treatment.

Objectives: The HIV/AIDS epidemic in China is growing and the main transmission mode has changed from contaminated blood products to sexual contact. The aim of this study was to evaluate the levels of anxiety (SAS; Zung Self-Rating Anxiety Scale) and depression (CES-D; Center for Epidemiologic Studies Depression Scale) among people living with HIV/AIDS (PLWHA) under the new epidemic characteristics and to examine associated factors. Methods: The sample size (N = 800) was calculated on the basis of the lowest prevalence of psychological disorders among PLWHA and was enlarged taking into consideration a loss of response. Participants were sampled randomly among all PLWHA registered in Liaoning Province. Questionnaires pertaining to the SAS, CES-D, and related factors were distributed between December 2010 and April 2011; 772 effective responses were received. Results: The prevalence of anxiety (SAS ≥40) and depression (CES-D ≥16) were 49.0% and 73.1%, respectively. Multivariate logistic regression analysis revealed that SAS was associated with self-rated health, condom use at the last sexual contact, perceived social support, alcohol consumption, and transmission; CES-D was associated with self-rated health, perceived social support, job, and sex. Conclusions: PLWHA under the new epidemic characteristics in China suffer from serious psychological problems. To improve their psychological well-being, efforts should be focused on improving perceptions of their health condition and increasing perceived social support.

This paper presents a fully differential single-axis accelerometer fabricated using the MetalMUMPs process. The unique structural configuration and common-centriod wiring of the metal electrodes enables a fully differential sensing scheme with robust metal sensing structures. CoventorWare is used in structural and electrical design and simulation of the fully differential accelerometer. The MUMPs foundry fabrication process of the sensor allows for high yield, good process consistency and provides 20 μm structural thickness of the sensing element, which makes the capacitive sensing eligible. In device characterization, surface profile of the fabricated device is measured using a Veeco surface profilometer; and mean and gradient residual stress in the nickel structure are calculated as approximately 94.7 MPa and −5.27 MPa/μm, respectively. Dynamic characterization of the sensor is performed using a vibration shaker with a high-end commercial calibrating accelerometer as reference. The sensitivity of the sensor is measured as 0.52 mV/g prior to off-chip amplification. Temperature dependence of the sensing capacitance is also characterized. A −0.021fF/°C is observed. The findings in the presented work will provide useful information for design of sensors and actuators such as accelerometers, gyroscopes and electrothermal actuators that are to be fabricated using MetalMUMPs technology.