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Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.

Lipid metabolism in cancer refers to the alterations in how cancer cells process and utilize lipids, a type of fat molecule. It was investigated how lipid metabolism relates to osteosarcoma. Genes relevant to lipid metabolism were gathered to create lipid metabolism-associated clusters and locate the dangerous marker. We investigated FAAH's prognostic significance, route annotation, immunotherapy response, and medication prediction. Besides, FAAH is proven to be a potent, dangerous marker that may promote growth and migration and inhibit the apoptosis of osteosarcoma. FAAH exhibits higher expression levels in tumor tissues as compared to normal tissues. In conclusion, FAAH is identified in this work as a potentially dangerous gene and immunotherapy determinant. This study requires more investigation to determine how FAAH influences the immune response in osteosarcoma.

Bionic trabecular bone scaffolds (Bio-Tb-S), which mimic the human cancellous bone, are widely recognized as the most effective repair material for large bone defects. Nevertheless, in situations with bone defects located in high-stress areas with intricate and varying mechanical environments, the scaffold necessitates reinforcement to withstand the limit stress. Achieving a balance between the “mechanical load-bearing properties, elastic modulus, and permeability” represents a substantial challenge. A scaffold with locally personalized reinforced was proposed based on slime mould algorithm (SMA), called bionic trabecular bone scaffold with slime mould algorithm (Bio-Tb-S-SMA), that is capable of echoing hard tissue characteristics. Additive manufacturing (AM) was utilized to fabricate the scaffold owing to its superior manufacturing flexibility. Compression tests, friction tests and bidirectional fluid–structure interaction experiments to evaluate the mechanical load-bearing properties, service stability, and permeability of scaffold. The results demonstrate that Bio-Tb-S-SMA effectively adapts to the complex in vivo stress environment, exhibiting strong bone-bearing capacity and service stability, while simultaneously retaining excellent permeability. Bio-Tb-S-SMA has broad potential for use as a bone repair material, and the bionic design and bionic reinforcement algorithm inject new vitality into the field of tissue engineering.

Abstract Background A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) is involved in inflammation and fertility in women with polycystic ovary syndrome (PCOS). This study aims to assess the role of ADAMTS level in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with PCOS, using a meta-analytic approach. Methods We systematically searched Web of Science, PubMed, EmBase, and the Cochrane library to identify potentially eligible studies from inception until December 2021. Study assess the role of ADAMTS levels in patients with PCOS was eligible in this study. The pooled effect estimates for the association between ADAMTS level and IVF-ET outcomes were calculated using the random-effects model. Results Five studies involving a total of 181 patients, were selected for final analysis. We noted that ADAMTS-1 levels were positively correlated to oocyte maturity (r = 0.67; P = 0.004), oocyte recovery (r = 0.74; P = 0.006), and fertilization (r = 0.46; P = 0.041) rates. Moreover, ADAMTS-4 levels were positively correlated to oocyte recovery (r = 0.91; P = 0.001), and fertilization (r = 0.85; P = 0.017) rates. Furthermore, downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was associated with elevated follicle puncture (ADAMTS-1: weighted mean difference [WMD], 7.24, P 0.05). Conclusions This study found that the outcomes of IVF-EF in patients with PCOS could be affected by ADAMTS-1 and ADAMTS-4; further large-scale prospective studies should be performed to verify these results.

Abstract Problem Background Penicillin was the first and most famous fungal secondary metabolite used as broad spectrum antibiotic that revolutionarised pharmaceutical research and also saved millions of lives. The over optimistic belief in 1967 that sufficient antibiotics had been discovered to defeat infectious diseases was quickly crashed with the appearance of multidrug resistant (MDR) bacteria in 1990s. This has posed a serious threat to mankind. Although scientists are making efforts to synthesize and discover new antibiotics there are not enough new drugs in pharmaceutical pipeline to beat the pace at which MDR bacteria are emerging. In view of this there is an urgent and serious medical need for new bioactive compounds to be discovered to treat infections caused by MDR pathogens. The present study is aimed to investigate the antibacterial potential of Aspergillus flavus originated compounds that may act as drug leads to treat future infections. Methodology Among the 6 isolated fungal strains from the rhizosphere of Mentha piperetta, one was processed for isolation of secondary metabolites on the basis of preliminary antibacterial testing. Observation of morphological and microscopic features helped in identification of the fungal strain as Aspergillus flavus. Potato Dextrose Agar (PDA) medium was used for fungal growth while Czapec Yeast Broth (CYB) medium was used for production of fungal metabolites. Column chromatography technique was utilized for purification of compound from crude fungal extract and the mass of the compound was determined using Liquid Chromatography Mass Spectrometry (LCMS) method. Structure elucidation of the pure compound was performed using 500 Varian Nuclear Magnetic Resonance (NMR) machine. Docking was performed using Glide SP algorithm. Agar well diffusion method was used to determine the invitro antibacterial potential of the compound against two MDR bacterial strains i.e. Staphylococcus aureus and Proteus vulgaris. For this a total of 4 dose concentrations i.e. (100, 250, 500, 1000 μg mL− 1) of the compound were prepared and applied to bacterial strains on Mueller Hinton agar using tetracycline as control. Results The chemical name of the purified compound from A. flavus was determined as (2E)-3-[(3S, 4R)-8-hydroxy-3, 4-dimethyl-1-oxo-3, 4-dihydro-1H-2- benzopyran-7-yl] prop-2-enoic acid with the formula C14H14O5 and exact mass of 262.08. The in-Silico analysis showed that this compound has the potential to inhibit the binding pocket of S. aureus TyrRS (1JII) with docking score of − 8.67 Kcal mole− 1. The results obtained from invitro experiments were encouraging as at 1000 μg mL− 1 the compound showed 58.8% inhibition against S. aureus and 28% inhibition against P. vulgaris. Conclusions The pure compound with formula C14H14O5 and exact mass of 262 exhibited antibacterial potential both insilico and invitro against both Gram negative and Gram positive bacteria. The compound was more active against S. aureus in comparison to P. vulgaris. From the obtained results it is concluded that this compound can be used as potent antibacterial candidate but further studies will be needed prior to its use as antibiotic.

BackgroundOsteosarcoma remains to be the most devastating malignant tumor in children and teenagers. Mitochondria have also been proven to play critical roles in osteosarcoma. However, a mitochondria-related signature has been established in osteosarcoma to comprehensively evaluate the pathogenic roles and regulatory roles of mitochondria in osteosarcoma.MethodsIn this study, osteosarcoma samples' transcriptome data and clinical information were collected from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. A comprehensive bioinformatics analysis was performed on the samples at the bulk RNA sequencing level and single-cell RNA sequencing (scRNA-seq) level. EdU, Transwell, and immunohistochemistry (IHC) were performed on PCCB.ResultsA mitochondria-related signature was constructed in osteosarcoma patients. The prognostic value of the mitochondria-related signature was explored. The predictive value of the mitochondria-related signature in the immune microenvironment and chemotherapy agents was explored. The association between mitochondria and immunity in the tumor microenvironment of osteosarcoma at the scRNA-seq level was investigated. The tumorigenic role of the critical mitochondria-related gene, PCCB, was verified by in vitro validation.ConclusionIn conclusion, a mitochondria-related signature was developed in osteosarcoma with solid predictive values in the immune microenvironment, chemotherapy agents, and prognosis.

Sea buckthorn leaves have been used for tea making in food field gradually. This study was carried out to characterize the bioactive polyphenols and volatile compounds in sea buckthorn leaves (SL), sea buckthorn leaves green tea (SGT), and sea buckthorn leaves black tea (SBT) by using high-performance liquid chromatography with an UV detector (HPLC-UV), the liquid chromatography-mass spectrometry (LC-MS), and headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS), in combination with multivariate analysis. A total of 48 non-volatile metabolites and 295 volatile metabolites were identified. Then, the total polyphenol and total flavonoid contents in SL, SGT, and SBT were also analyzed. Moreover, SL and SGT showed greater antioxidant activities based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and oxygen radical absorbance capacity (ORAC) results. At the concentration of 0.1 mg/ml, their DPPH and ABTS radical scavenging ratios were 66 to 95%, while SBT exhibited lower antioxidant activity of 26 to 44%. SL, SGT, and SBT displayed moderate α-glucosidase inhibitory activity.

Hydrogel is a porous three-dimensional network material that is insoluble in water and can store a large amount of water. This material has excellent mechanical properties, such as medical fields, wastewater treatment and other fields, and are widely used. With the development of modern science and technology, the research on hydrogel, a new kind of biomaterial, is increasingly extensive. Many researchers have carried out research on bone tissue-related engineering based on the advantages of hydrogel, such as adjustable mechanical properties, convenient production and combination with bioactive factors. The researchers mainly focus on the mechanical properties and biocompatibility of hydrogel made of composite materials. The disease causes extensive trauma, broken bones and cartilage damage that does not heal on its own, while traditional surgical treatments can bring side effects such as infection, inflammation and pain. As a new kind of biomaterial, hydrogel has controllable mechanical properties and biocompatibility, and is widely used in bone tissue engineering as scaffold material for growth factor transport and cell adhesion. In order to make hydrogels more suitable for local treatment of orthopedic diseases, the excellent properties of hydrogels are combined with synthetic materials with advanced technologies in different fields. In this paper, the test methods used in the study of mechanical and tribological properties of bone repair hydrogels are reviewed, and the shortcomings of experimental methods in the study of cartilage repair hydrogels are pointed out. the application of the combination of mechanics and tribology in the study of cartilage repair and cartilage replacement was discussed, and the research progress of molecular dynamics in characterizing the micromechanical state of hydrogel was summarized.

Oats (Avena sativa L.) with similar amylose content were used to investigate the effects of ultra-high pressure treatment (UHPT) on the eating quality of steamed oat and oat protein structure. Water absorption and texture of steamed oat were evaluated and taste analysis was conducted by electronic tongue after a series of UHPT (400–600 MPa; holding time 5–15 min). The oat protein was extracted from the oat and treated with the same UHPT as the steamed oat (400–600 MPa; holding time 5–15 min). The oat protein structure was scanned by scanning electron microscopy (SEM). The water absorption rate of oat rice was increased by UHPT. Hardness values of steamed oat were reduced while springiness and cohesiveness were increased by UHPT. The UHPT samples showed significant differences in electronic tongue profiles from that of the original samples. The SEM results indicated that the structure of the protein was greatly affected by UHPT. The impact on protein structure significantly increased with an increasing level of pressure and treatment time. In general, the UHPT has strong potential to improve the texture and flavor of oat and change the structure of oat protein during industrial production.

Abstract Background Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potential anti-atherosclerotic effects by preventing Oxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protective effects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury. Methods OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined by high performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. The effect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM). Results 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes. Conclusion OA could reduce inflammation, protect endothelial cells and play an anti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.

Background: Abnormal lipid accumulation in macrophages may lead to macrophages foaming, which is the most important pathological process of atherosclerosis. Atmospheric PM2.5 could enter the blood circulation and further affect the lipid metabolism of macrophages. But the underlying mechanism is not unclear. This study was undertaken to clarify the effect of PM2.5 on lipid metabolism in macrophages, and to explore the role of inflammatory reaction and JAK2/STAT3 signaling pathway in this process. Method: Macrophages derived from THP-1 cells were exposed to PM2.5 (0,100,200,400 μg/mL) for 6 h and 12 h. STAT3 agonist ColivelinTFA is used to specifically excite STAT3. The survival rate of macrophages was detected by CCK-8. The lipid levels in macrophages were detected by colorimetry. The levels of inflammatory factors secreted by macrophages were detected by ELISA. Q-PCR was used to detect the mRNA expression levels, and Western Blot was used to detect the protein expression levels of JAK2/STAT3 pathway genes. Result: The survival rate of macrophages was reduced by PM2.5, and the levels of TG, T-CHO and LDL-C of macrophages exposed to PM2.5 were increased. PM2.5 led to the increasing level of IL-6 and the decreasing level of IL-4, and the JAK2/STAT3 signaling pathway was inhibited by PM2.5. Colivelin TFA significantly decreased the increasing levels of TG, T-CHO and LDL-C levels, and increased the decreasing mRNA levels of IL-4, and LPL induced by PM2.5 (p

Abstract Background Shunxinzufang decoction is tutors, empirical formula and has been used in Chinese patients of HFpEF for several years. The aim of this study was to make into sustained release granules and select the best formula for the preparation of Shunxin sustained release granules and to evaluate its in vivo and in vitro drug release behavior. Methods Response surface methodology and Center composite design were applied to screen the optimal formula of Shunxin sustained release granules. HPLC was used to detect indicative ingredients—paeoniflorin, calycosin-7-glucoside and ferulic acid in Shunxin sustained release granules. The in vitro sustained release character of indicative ingredients was investigated in simulated digestive fluids. In-vivo process of active components was studied through pharmacokinetics. Results The optimal formula of Shunxin sustained release granules consisted of 35% shunxinzufang extract and 65% HPMC/starch (HPMC/starch ratio = 2:1). Three indicative components can be separated well under selected HPLC conditions. Compared with Shunxinzufang extract, the active components of Shunxin sustained release granules have obvious sustained-release character and improved bioavailability. Conclusion Shunxin sustained release granules has obvious sustained-release character and improved bioavailability.

Abstract Background Epidemiological studies have confirmed atmospheric PM2.5 could affect asthma, and dyslipidemia may be related to pathogenesis of asthma. Recent studies show Notch ligands had lipid combination domains which are responsible for regulating lipid levels. However, the effect of PM2.5 on asthmatic rats’ lipid levels and the role of Notch signaling pathway is unclear. Methods Rats were treat with ovalbumin (OVA) to establish asthma models. Notch signaling pathway inhibitor (DAPT) was injected intraperitoneally. Asthmatic and healthy rats were exposed to different concentrations of PM2.5. Lung tissues were collected and the expression of Hes1 protein was detected by Western Blot. Blood samples were collected to detect the serum lipid levels. Results Hes1 expression levels in healthy and asthma pathway inhibition groups were lower than those in control groups. Compared with control group, rats exposed to PM2.5 in middle and high dose, the levels of TG and TC were decreased. Similar results were observed after exposure to the same concentration of PM2.5 in asthmatic rats. Rats, which were exposed to PM2.5 after being established the asthma model successfully, could exhibit more significant dyslipidemia than those with direct exposure. After Notch signaling pathway inhibited, TC and LDL in asthma pathway inhibition group were lower than those in healthy group. Conclusions PM2.5 can affect the lipid levels of asthmatic rats through the Notch signaling pathway.

Abstract Novel compounds and more efficient treatment options are urgently needed for the treatment of cystic echinococcosis (CE), which is caused by Echinococcus granulosus. The decoction of Sophora moorcroftiana (Fabaceae) has been used to treat parasitosis for years in traditional Tibetan medicine. The aim of this study was to screen insecticidal water-soluble alkaloids from S. moorcroftiana seeds and evaluate the therapeutic effects against CE and the immune response induced by the alkaloidal fraction. Low polarity compounds (E2-a) were isolated from water-soluble alkaloid (E2) and matrine and sophocarpine were identified as major components. The E2-a fraction was more effective against protoscoleces than other constituents from S. moorcroftiana. After 20 weeks of secondary infection with protoscoleces, mice were orally treated with E2-a (100 mg/kg/day) for 6 weeks to evaluate therapeutic and immunoregulatory activities. Compared with the untreated group, E2-a treatment induced a significant reduction in cyst weight (mean 2.93 g) (p

Background: Mono-2-ethylhexyl phthalate (MEHP) is a major metabolite of di (2-ethylhexyl) phthalate (DEHP). Our previous researches have shown that MEHP can induce lipid accumulation in preadipocytes, while, the underlying mechanism is unclear. The present study was undertaken to clarify the effect of Notch pathway on lipid accumulation induced by MEHP. Methods: 3T3-L1 preadipocytes were exposed to MEHP (0, 10, 50, 250 µM and 0.1%DMSO) for the whole differentiation phase. Then the level of TG and cell cycle were detected. RT-PCR was used to detect the mRNA expression and Western blot was used to detect the expression of protein by Notch pathway genes and lipid metabolic related genes. Results: In this study, the level of TG in the 250 µM and 250 µM MEHP groups was significantly higher than that in the control, DMSO and 10 µM MEHP groups (P

Autologous or allogeneic bone grafts are common methods to treat bone defects. Bone tissue engineering combining carrier material with the active factor can induce a generation of new bone at the bone defect site. However, its clinical application is restricted by the limited donors, the high morbidity at the donor site, the low activity in vivo, and dose-independent adverse effect. To overcome the limitations of traditional therapies, it is urgent to find and develop a repair material that can replace natural bones. Hence, we designed and prepared suitable MPEG-PCL microspheres loaded bone morphogenetic protein-2 (BMP-2/MPEG-PCL-MS) to effectively solve the problem mentioned above, prolong its reaction time at the targeted site, and avoid the pain of patients caused by frequent administration. The physicochemical properties and in vitro release behaviors were good. The microspheres showed high biocompatibility and strongly induced osteogenesis in vivo. BMP-2/MPEG-PCL-MS has been proven to exert sustained-release in vivo and maintain the inherent BMP-2 activity. They can be directly injected into the bone defect site, or implanted to a large bone defect site together with stent material to exert therapeutic effects. Hence, this smart drug delivery system has promising potential for clinical applications and provides a well-controlled design for combination of tissue engineering and pharmaceutics for further exploration.

Hot stamping components with tailored mechanical properties have excellent safety-related performance in the field of lightweight manufacturing. In this paper, the constitutive relation and damage evolution of bainite, martensite, and mixed bainite/martensite (B/M) phase were studied. Two-dimensional representative volume element (RVE) models were constructed according to microstructure characteristics. The constitutive relations of individual phases were defined based on the dislocation strengthening theory. Results showed that the damage initiation and evolution of martensite and bainite phases can well described by the Lou-Huh damage criterion (DF2015) determined by the hybrid experimental–numerical method. The calibrated damage parameters of each phase were applied to the numerical simulation, followed by the 2D RVE simulations of B/M phase under different stress states. To study the influence of martensite volume fraction (Vm) and distribution of damage evolution, the void nucleation and growth were evaluated by RVEs and verified by scanning electron microscope (SEM). Three types of void nucleation modes under different stress states were experimentally and numerically studied. The results showed that with the increase of Vm and varying martensite distribution, the nucleation location of voids move from bainite to martensite.

Bone defects are a major threat to human health, and heterotopic bone provides advantages that other materials do not provide in the treatment of bone defects. MPEG-PCL microspheres loaded with bone morphogenetic protein-2 (BMP-2/MPEG-PCL-MS) are an emerging means of culturing heterotopic bone. However, the effect of such microspheres on the quality of heterotopic bone osteogenesis has rarely been studied. The performance of heterotopic bone as a bone repair material has also rarely been reported. To explore the effect of microspheres on heterotopic bone osteogenesis and to explore the performance of heterotopic bone in bone repair, we designed compression tests, nanoindentation tests, and a finite element (FE) simulation. The effects of microspheres on the quality of heterotopic bone osteogenesis and performance of heterotopic bone as a bone repair material were evaluated from the mechanical properties, material properties, and FE simulation. The results demonstrate that eight-week heterotopic bone using microspheres has suitable mechanical and material properties, performs well in bone repair FE simulation, and can meet the material requirements of bone repair. Hence, this heterotopic bone as bone repair material has promising potential for clinical applications, and provides a good strategy for combination between tissue engineering and pharmaceutical science.

The CNT-PDMS composite has been widely adopted in flexible devices due to its high elasticity, piezoresistivity, and biocompatibility. In a wide range of applications, CNT-PDMS composite sensors were used for resistive strain measurement. Accordingly, the percolation threshold 2%~4% of the CNT weight ratio in the CNT-PDMS composite was commonly selected, which is expected to achieve the optimized piezoresistive sensitivity. However, the linear range around the percolation threshold weight ratio (2%~4%) limits its application in a stable output of large strain (>20%). Therefore, comprehensive understanding of the electromechanical, mechanical, and electrical properties for the CNT-PDMS composite with different CNT weight ratios was expected. In this paper, a systematic study was conducted on the piezoresistivity, Young’s modulus, conductivity, impedance, and the cross-section morphology of different CNT weight ratios (1 to 10 wt%) of the CNT-PDMS composite material. It was experimentally observed that the piezo-resistive sensitivity of CNT-PDMS negatively correlated with the increase in the CNT weight ratio. However, the electrical conductivity, Young’s modulus, tensile strength, and the linear range of piezoresistive response of the CNT-PDMS composite positively correlated with the increase in CNT weight ratio. Furthermore, the mechanism of these phenomena was analyzed through the cross-section morphology of the CNT-PDMS composite material by using SEM imaging. From this analysis, a guideline was proposed for large strain (40%) measurement applications (e.g., motion monitoring of the human body of the finger, arm, foot, etc.), the CNT weight ratio 8 wt% was suggested to achieve the best piezoresistive sensitivity in the linear range.