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Abstract The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention. Nasal organoids are more susceptible to HRV-C than airway organoids. Intriguingly, upon HRV-C infection, we observe an innate immune response that is stronger in airway organoids than in nasal organoids, which is reproduced in a Poly(I:C) stimulation assay. Treatment with α-CDHR3 and antivirals significantly reduces HRV-C viral growth in airway and nasal organoids. Additionally, an organoid-based immunofluorescence assay is established to titrate HRV-C infectious particles. Collectively, we develop an organoid-based system to reproducibly propagate the poorly cultivable HRV-C, followed by a comprehensive characterization of HRV-C infection and innate immunity in physiologically active respiratory organoids. The organoid-based HRV-C infection model can be extended for developing antiviral strategies. More importantly, our study has opened an avenue for propagating and studying other uncultivable human and animal viruses.

Abstract Background Jiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease. Methods BV‐2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid‐β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐B (NF‐κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration. Results The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL‐1β, TNF‐α, and iNOS; increased the expression level of IL‐10; and significantly decreased the phosphorylation levels of MAPK and NF‐κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL‐1β and TNF‐α in the cortex were significantly downregulated after JHP administration, whereas IL‐10 showed increased expression. Conclusions It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF‐κB signaling pathway.

High-power microwave (HPM) antenna, one of the key subsystems in the HPM system, is used for HPM radiation. Its performance is partly determined by the impulse responses of reflector materials under HPM. Therefore, it is essential to investigate the impulse response characteristics of reflector materials under HPM. Instead of the traditional waveguide cavity, this study was based on the double elliptical reflector system with an open boundary. By using this system, the impulse response of reflector materials was measured, and the response of reflector materials of multiple types under various environments with different electric field strengths and pulse widths was tested. In terms of breakdown, reflection efficiency, and pulse waveform, aluminum and carbon fiber test plates were affected by HPM and compared. Finally, the impulse response characteristics of carbon fiber test plates were summarized. The proposed method applied in this research is universal, matches the practical application environment, and can be extensively employed in the impulse response research and test of reflector materials.

Context Shenlian extract (SL) is a combination of Salvia miltiorrhiza Bge. (Labiatae) and Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts, which promote blood circulation and clear endogenous heat toxins. Myocardial ischaemia-reperfusion injury (MI/RI) is aggravated myocardial tissue damage induced by reperfusion therapy after myocardial infarction.Objectives This study explores the effect of SL on MI/RI and the underlying mechanism.Materials and methods Primary peritoneal macrophages (pMACs) were treated with LPS and SL (5, 10 or 20 μg/mL) for 24 h. The myocardial ischaemia-reperfusion (MI/R) model was established after administration of different doses of SL (90, 180 or 360 mg/kg). Myocardial tissue injury was assessed by methylthiazolyl tetrazolium (TTC) staining and levels of creatine kinase (CK), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in mice. The double immunofluorescence staining of iNOS/F4/80 and CD86/F4/80 was used to detect macrophage M1 polarization. The levels of miR-155, inflammatory factors and chemokines were detected by qRT-PCR or ELISA. CD86, iNOS, SOCS3, JAK2, p-JAK2, STAT3 and p-STAT3 proteins expressions in macrophages were analyzed by western blotting. Conditioned medium transfer systems were designed to unite M1 macrophages with H/R cardiomyocytes, and cell apoptosis was detected by TUNEL staining, western blotting or immunohistochemistry.Results SL reduced apoptosis, diminished CK and LDH levels, raised SOD concentration and decreased infarct size in the MI/R model. Meanwhile, SL decreased miR-155 level, inhibited M1 macrophage polarization and inflammation. Furthermore, SL promoted SOCS3 expression and blocked JAK2/STAT3 pathway in vitro.Conclusions SL may be a promising TCM candidate for MI/RI. The underlying mechanisms could be associated with inhibition of M1 macrophage polarization via down-regulating miR-155.

In response to the low soil breakage rate and poor flatness of current combined soil preparation equipment for growing potatoes under the clay loam conditions of Northeast China, this paper presents the design of an arc-shaped tooth press device for such equipment, describing its overall structure and working principle. By conducting force analysis on the press roller and shear stress analysis with MATLAB, we obtained the structural parameters and the corresponding value ranges impacting the operational effectiveness of the press device. A three-factor, five-level quadratic regression orthogonal rotational combination test was carried out using EDEM discrete element simulation software, taking the soil breakage rate and flatness as the test indicators. The forward speed, roller tooth arc length, and angle between the roller tooth and the vertical direction (ABRTVD) were the test factors. Design-Expert 8.0.6 software was used for data processing and analysis, and the results showed that the optimal parameter combination consisted of a forward speed of 0.72~1.15 m·s−1, a roller tooth arc length of 58.7 mm, and an ABRTVD of 37.74°, at which point the soil breakage rate was 93.58% and the flatness value was 21.36 mm. The optimal combination of parameters was selected for the field test, resulting in a soil breakage rate of 95.6% and a flatness value of 20.6 mm. The results of the simulation test were found to be consistent with the field test results, thus validating the efficacy of the device design. The findings of this study can provide a reference for enhancing the operational performance of combined soil preparation equipment for growing potatoes under clay loam conditions.

The respiratory epithelium, particularly the airway epithelium, is the primary infection site for respiratory pathogens. The apical surface of epithelial cells is constantly exposed to external stimuli including invading pathogens. Efforts have been made to establish organoid cultures to recapitulate the human respiratory tract. However, a robust and simple model with an easily accessible apical surface would benefit respiratory research. Here, we report the generation and characterization of apical-out airway organoids from the long-term expandable lung organoids that we previously established. The apical-out airway organoids morphologically and functionally recapitulated the human airway epithelium at a comparable level to the apical-in airway organoids. Moreover, apical-out airway organoids sustained productive and multicycle replication of SARS-CoV-2, and accurately recapitulated the higher infectivity and replicative fitness of the Omicron variants BA.5 and B.1.1.529 and an ancestral virus. In conclusion, we established a physiologically relevant and convenient apical-out airway organoid model for studying respiratory biology and diseases.

The Wuji pill, also called Wuji Wan (WJW), is an effective traditional medicine for the clinical treatment of irritable bowel syndrome (IBS). It is principally composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, and Radix Paeoniae Alba. There have been no reports on the pharmacokinetics of WJW on IBS. Because it is more meaningful to study pharmacokinetics in relation to specific pathological conditions, our study investigated the pharmacokinetic differences of five representative components (berberine, palmatine, evodiamine, rutaecarpine, and paeoniflorin) in normal rats and chronic visceral hypersensitivity IBS (CVH-IBS) model rats after single dose and multiple doses of WJW using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy, immunohistochemistry, and immunofluorescence were used to explore mechanisms behind the pharmacokinetic differences in terms of tight junction proteins (Occludin and ZO-1), myosin light chain kinase (MLCK), and transporters including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and multidrug resistance associated protein 2 (MRP2) in rat colons. After a single dose, for all components except rutaecarpine, significant differences were observed between normal and model groups. Compared with normal group, T1/2 and AUC0-t of berberine and palmatine in model group increased significantly (562.5 ± 237.2 vs. 1,384.9 ± 712.4 min, 733.8 ± 67.4 vs. 1,532.4 ± 612.7 min; 5,443.0 ± 1,405.8 vs. 9,930.8 ± 2,304.5 min·ng/ml, 2,365.5 ± 410.6 vs. 3,527.0 ± 717.8 min·ng/ml), while Cl/F decreased (840.7 ± 250.8 vs. 397.3 ± 142.7 L/h/kg, 427.7 ± 89.4 vs. 288.9 ± 114.4 L/h/kg). Cmax and AUC0-t of evodiamine in model group increased significantly (1.4 ± 0.6 vs. 2.4 ± 0.7 ng/ml; 573 ± 45.3 vs. 733.9 ± 160.2 min·ng/ml), while T1/2, Tmax, Cl/F, and Vd/F had no significant difference. Tmax and AUC0-t of paeoniflorin in model group increased significantly (21.0 ± 8.2 vs. 80.0 ± 45.8 min; 15,428.9 ± 5,063.6 vs. 33,140.6 ± 5,613.9 min·ng/ml), while Cl/F decreased (110.5 ± 48.1 vs. 43.3 ± 9.5 L/h/kg). However, after multiple doses, all five components showed significant differences between normal and model groups. Moreover, these differences were related to tight junction damage and the differential expression of transporters in the colon, suggesting that dose adjustment might be required during administration of WJW in the clinical treatment of IBS.

Abstract Background This research sought to determine the impact of explicit program-based development of skills associated with research and Evidence Based Practice (EBP) on the attitudes and sustained behaviours of graduates subsequently employed in clinics. Systematic reviews have shown that university teaching of EBP and research skills rarely result in transfer of commensurate attitudes and sustained behaviours of students to their subsequent studies or to employment. Studies have therefore called for detailed exploration of what may enable this transfer of knowledge and skills to attitudes and behaviours. In keeping with these calls, this paper presents a fine-grained qualitative study of graduates’ research skills and EBP in clinics with particular reference to pertinent attitudes, values and behaviours sustained, or further developed, one year after program completion. Methods The study revolved around employed graduates of a Bachelor of Oral Health (BOH) program, which used the Research Skill Development (RSD) framework to structure the explicit, coherent and cyclic development of the skills associated with research in multiple semesters of the degree. One year after their completion of the BOH program, semi-structured interviews were conducted with nine employed graduates, three from each of three consecutive cohorts, to gain their professional perspectives on their research skills and EBP developed at university and then used in clinics. While the pre-determined interview questions focused on employed graduates’ knowledge and skills, the attitudes and values around research skills and EBP emerged spontaneously. Results Graduates that were interviewed relayed in detail their attitudes and values associated with research skills and EBP when asked about their work in clinics, even though the affective elements were not specifically elicited. In the employment context, the positive affective aspects of the skills associated with research and EBP that graduates discussed were pronounced, and this contrasted with working graduates retrospective view of university research skills and EBP. Conclusions The richness of affective interaction with patients was a factor that enabled the interviewed graduates to transfer university knowledge and skills into attitudes and behaviours associated with EBP. We recommend similar fine-grained qualitative research to further develop constructs that enable quantification of the interplay of cognitive and affective facets in researching and EBP.

Metastasis is a multistep process that depends on the interactions between tumor cells and their microenvironment. Macrophages in the tumor microenvironment show high polarization plasticity and have a paradoxical role in cancer progression. Hijacked by tumor-promoting signals, the polarization status of macrophages was pathologically disturbed and believed to be the decisive mechanism forcing the progression of metastasis. In this study, we explored the immunological activity of Chamaejasmin B (ICJ), a previously proved inhibitor for metastasis, in macrophages from metastatic microenvironment. When intravenously injected of 4T1 cells in mice, ICJ significantly inhibited its metastatic outgrowth. Taking tumor cell and macrophage as a functional integrity, an adoptive transfer model was established in vitro to exclude the direct effect of ICJ on tumor. The findings suggest a dual influence of ICJ on both tumors and macrophages, as indicated by the rebalance of macrophage polarization and suppression of clonogenic potential in tumor cells. Mechanistically, ICJ redirected M2-dominant polarization of tumor-associated macrophage in an IL-4-mTOR-dependent manner. Collectively, our study revealed that ICJ rebalanced macrophage polarization in malignant microenvironment and showed promising effect in suppressing metastatic outgrowth in breast cancer model.

The emission uniformity of an annular knife-edged cathode in a coaxial diode with a focusing electrode and operating in a low macro electric field has been investigated. It was found that the emission uniformity deteriorated as the cathode width increased from 0.5 mm to 2.0 mm. To improve the emission uniformity, a grooved graphite cathode was prepared by a laser micro-etching treatment. Experimental results demonstrated that the emission threshold for the grooved cathode may be reduced and thus the delay in explosive emission can be decreased. Visual inspection of photographs of the cathode plasmas operating under different guiding magnetic fields (GMFs) was used to confirm improvements in emission uniformity. Even under a low GMF of 0.21 T, good emission uniformity was realized.

In the case of characterizing waveguide mode converter, the widely applied back-to-back method can only extract two mode converters' joint S-parameters, the accuracy of the far-field radiation pattern method is limited. This paper experimentally demonstrates a method for accurately characterizing single circular TM01-TE11 mode converter, which consists of extracting the asymmetric two-port TM01 and TE11 mode generator test fixtures' S-parameters and de-embedding them from the “TM01 mode generator + TM01-TE11 mode Converter + TE11 mode generator” cascade measurement results. The peak problem occurring in measuring overmoded circular waveguide devices with VNA is analyzed and settled with an offset waveguide based peak-shifting tactic plus the Loess smoothing method. Fairly good agreement between the simulated and finally extracted complex S-parameter matrix of a TM01-TE11 mode converter throughout the device's working frequency span validates the proposed method's merits over traditional methods.

Conservation tillage technology can reduce wind erosion and soil erosion, improve soil fertility, avoid straw burning and relieve ecological pressure. It is an important measure to achieve sustainable agricultural development. In northeast China, there is a large amount of straw covering the ground after the corn machine harvest, which can easily lead to the blockage of the soil-touching parts during no-tillage seeding, affecting sowing quality and crop yield. In order to solve the above problems, the clearing and covering of a minimum-tillage planter for corn stubble was developed. The machine can complete multiple processes, such as seedbed preparation, seeding, fertilization, covering and suppression, straw covering, etc., in a single entity. This paper focuses on the design of the straw cleaning device and uses discrete element method software (EDEM 2018, Altair Engineering, Troy, MI, USA) to establish the straw cleaning device–straw–soil discrete element simulation model. The quadratic-regression orthogonal center-of-rotation combination test method is used to optimize the parameter combination of the machine, using the operating speed, the speed of the knife roller and the penetration depth of the knife as the test factors and using the rate of cleaning straw and the equivalent power consumption as the evaluation index. The results show that each factor has a significant influence on the performance evaluation indices, and the order of influence of each factor on the rate of cleaning straw is operation speed > penetration depth of knife > speed of knife roller, and the order of influence of each factor on the equivalent power consumption is penetration depth of knife > speed of knife roller > operation speed. The optimal combination of parameters is a 5.5–6.2 km/h operation speed, a 500 rpm speed of the knife roller, a 40 mm penetration depth of the knife, a straw-cleaning rate of more than 90% and an equivalent power consumption of less than 8 kW. This study provides technical and equipment support for the promotion of conservation tillage technology in Northeast China.

Background/Aim: Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques.Methods: The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE−/− mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining.Results: Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE−/− mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL.Conclusion: Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability.

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI.Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors.Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition.Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.

Besides pathogen evading, Acute Lung Injury (ALI), featuring the systematic inflammation and severe epithelial damages, is widely believed to be the central non-infectious factor controlling the progression of infectious diseases. ALI is partly caused by host immune responses. Under the inspiration of unsuccessful treatment in COVID-19, recent insights into pathogen–host interactions are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. The interaction unit consisting of macrophages and the alveolar epithelial cells has recently revealed as the therapeutic basis targeting ALI. Lian Hua Qing Wen capsule is the most effective and commonly-used clinical formula in treating respiratory infection for thousands of years in China. However, little is known about its relevance with ALI, especially its protective role against ALI-induced alveolar tissue damages. Aiming to evaluate its contribution in antibiotics-integrating therapies, this study pharmacologically verified whether LHQW could alleviate lipopolysaccharide (LPS)-induced ALI and explore its potential mechanisms in maintaining the physiology of macrophage-epithelial unit. In ALI mouse model, the pathological parameters, including the anal temperature, inflammation condition, lung edema, histopathological structures, have all been systematically analyzed. Results consistently supported the effectiveness of the combined strategy for LHQW and low-dose antibiotics. Furthermore, we established the macrophages-alveolar epithelial cells co-culture model and firstly proved that LHQW inhibited LPS-induced ER stress and TRAIL secretion in macrophages, thereby efficiently protected epithelial cells against TRAIL-induced apoptosis. Mechanistically, results showed that LHQW significantly deactivated NF-κB and reversed the SOCS3 expression in inflammatory macrophages. Furthermore, we proved that the therapeutic effects of LHQW were highly dependent on JNK-AP1 regulation. In conclusion, our data proved that LHQW is an epithelial protector in ALI, implying its promising potential in antibiotic alternative therapy.

This paper investigates the dependence of the properties of the spatial harmonics on the overmoded ratio of the corrugated waveguide operating in TM01 at 30 GHz with the consideration of the effects of the ripple shape. It is found that as the overmoded ratio grows, the electric fields concentrate towards the ripple surface, which weakens the enhancement of the power handling capacity caused by augmentation of the overmoded ratio. As the overmoded ratio grows, the ratio between the field amplitudes of the -1st spatial harmonic and the fundamental harmonic increases monotonically. Therefore, the total electric fields composed of the spatial harmonics become the spatial beating-wave with the single frequency, whose amplitudes vary along z-axis with the spatial period determined mainly by the -1st spatial harmonic and the fundamental harmonic. Researches on coupling impedances show that with the same overmoded ratio, the corrugated waveguide consisting of the improved rectangular ripples provides better synchronous coupling for the wave-beam interaction than that of the sinusoidal ripples does. Moreover, it is better to choose the fundamental harmonic close to the light line as the synchronous wave for the wave-beam interaction in the low magnetic field. In that case, even if the electron beam keeps far away from the ripple surface, the synchronous wave still provides strong enough coupling for the electron beam.

Abstract Background MicroRNAs(miRNAs)are involved in the initiation and progression of hepatocellular carcinoma. ESC, an extract of Stellerachamaejasme L, had been confirmed as a potential anti-tumor extract of Traditional Chinese Medicine. In light of the important role of miRNAs in hepatocellular carcinoma, we questioned whether the inhibitory effects of ESC on hepatocellular carcinoma (HCC) were associated with miRNAs. Methods The proliferation inhibition of ESC on HCC cells was measured with MTT assay. The migration inhibition of ESC on HCC cells was measured with transwell assay. The influences of ESC on growth and metastasis inhibition were evaluated with xenograft tumor model of HCC. Protein expressions were measured with western blot and immunofluorescence methods and miRNA profiles were detected with miRNA array. Differential miRNA and target mRNAs were verified with real-time PCR. Results The results showed that ESC could inhibit proliferation and epithelial mesenchymal transition (EMT) in HCC cells in vitro and tumor growth and metastasis in xenograft models in vivo. miRNA array results showed that 69 differential miRNAs in total of 429 ones were obtained in MHCC97H cells treated by ESC. hsa-miR-107, hsa-miR-638, hsa-miR-106b-5p were selected to be validated with real-time PCR method in HepG2 and MHCC97H cells. Expressions of hsa-miR-107 and hsa-miR-638 increased obviously in HCC cells treated by ESC. Target genes of three miRNAs were also validated with real-time PCR. Interestingly, only target genes of hsa-miR-107 changed greatly. ESC downregulated the MCL1, SALL4 and BCL2 gene expressions significantly but did not influence the expression of CACNA2D1. Conclusion The findings suggested ESC regressed growth and metastasis of human hepatocellular carcinoma via regulating microRNAs expression and their corresponding target genes.

Xueshuantong capsule (XST) is a patented traditional Chinese medicine used for the prevention and treatment of thrombosis. The molecular mechanism of anti-thrombotic effect of XST was investigated through the cross-talk among the platelets/leukocytes, endothelial cells (ECs), and flow shear stress. The Bioflux 1000 system was used to generate two levels of shear stress conditions: 0.1 and 0.9 Pa. Bioflux Metamorph microscopic imaging system was used to analyze the adhesion cell numbers. Protein expressions were detected by western blotting and flow cytometry. The flow-cytometry results showed that under 0.1 Pa flow, XST decreased ADP induced platelets CD62p surface expression in a concentration-dependent manner. Under 0.9 Pa flow, XST at a concentration of 0.15 g⋅L-1 reduced the platelets activation by 29.5%, and aspirin (ASA) showed no inhibitory effects. XST showed similar efficiency on monocytes adhesion both under 0.1 and 0.9 Pa flow conditions, and the inhibition rate was 30.2 and 28.3%, respectively. Under 0.9 Pa flow, the anti-adhesive effects of XST might be associated with the suppression of VE-cadherin and Cx43 in HUVECs. Blood flow not only acts as a drug transporter, but also exerts its effects to influence the pharmacodynamics of XST. Effects of XST on inhibiting platelets activation and suppressing platelets/leukocytes adhesion to injured ECs are not only concentration-dependent, but also shear stress-dependent. The mechanic forces combined with traditional Chinese medicine may be used as a precise treatment for cardiovascular diseases.

The neovascularization functions essentially for malignant upgrading and predicts poor prognosis in multiple cancers, which make it the highly effective strategy for clinical treatment. Unfortunately, the known anti-angiogenic therapies show low effectiveness against breast cancer. Recently, rebalancing the pro-angiogenic property in microenvironment shows great advantages and attracts increasing attention for breast cancer treatment. Herein, we for the first time reported that Chamaejasmine B (ICJ), extracted from Stellera chamaejasme L., possessed potent anti-angiogenic effect in breast cancer. By Transwell, tube formation and aortic-ring assays, ICJ efficiently suppressed the neovascularization potential in tumor-HUVEC co-culture model. In Matrigel plug assay, the efficacy of ICJ was further identified in vivo. Mechanistically, with little influence on HUVEC apoptosis, ICJ obviously induced autophagy as proved by the elevated LC3I/II ratio, dotted distribution of LC3 and upregulated Beclin-1. Moreover, by associating with LC3 and in turn, inhibiting the level of VEGFR2, the anti-angiogenesis efficacy was closely dependent on the initiation of autophagy. Above results proved that, by attenuating the pro-angiogenic communication through VEGFR2, ICJ is a novel angiogenic inhibitor and will be a promising supplement for anti-angiogenic chemotherapy for breast cancer.

Emerging evidence suggests that gut microbiota contribute to the treatment of post-inflammatory irritable bowel syndrome (PI-IBS). Our previous studies have demonstrated that a Chinese formula, Wuji Wan, has the ability to mitigate abdominal pain and diarrhea in PI-IBS rats. However, little is known about the underlying mechanism and whether the gut microbiota mediate the effect of Wuji Wan on PI-IBS. Thus, the aim of this study was to determine whether Wuji Wan mitigated PI-IBS by modifying the gut microbiota. PI-IBS was induced in Sprague-Dawley rats by enema using 4% acetic acid and restraint stress. Rats were fed water, Wuji Wan extract (630 mg/kg) or pinaverium bromide (13.5 mg/kg). Our data showed that Wuji Wan effectively ameliorated abdominal pain, colonic motility abnormality and visceral hypersensitivity. Analysis of the fecal microbiota showed that Wuji Wan could reverse the reduction in richness of the gut microbiota and significantly increase the relative abundances of Akkermansia, Bacteroides, and Parasutterella; however, Lactobacillus and Prevotella were markedly decreased in the PI-IBS rats. Moreover, Wuji Wan promoted goblet cell proliferation in the colonic mucosa by increasing the release of mucin, up-regulating the distribution of tight junction proteins Occludin and ZO-1 and down-regulating the expression of MLCK in colonic epithelial cells. These findings suggest that Wuji Wan may remit IBS by modulating the gut microbiota and stabilizing the gut mucosal barrier, indicating that the use of a classical formula of Traditional Chinese Medicine (TCM) that exhibits a prebiotic effect may be a promising strategy for PI-IBS treatment.

We propose and demonstrate a novel method to produce few-femtosecond electron beam with relatively low timing jitter. In this method a relativistic electron beam is compressed from about 150 fs (rms) to about 7 fs (rms, upper limit) with the wakefield at THz frequency produced by a leading drive beam in a dielectric tube. By imprinting the energy chirp in a passive way, we demonstrate through laser-driven THz streaking technique that no additional timing jitter with respect to an external laser is introduced in this bunch compression process, a prominent advantage over the conventional method using radio-frequency bunchers. We expect that this passive bunching technique may enable new opportunities in many ultrashort-beam based advanced applications such as ultrafast electron diffraction and plasma wakefield acceleration with externally injected beam.

Streaking of photoelectrons with optical lasers has been widely used for temporal characterization of attosecond extreme ultraviolet pulses. Recently, this technique has been adapted to characterize femtosecond x-ray pulses in free-electron lasers with the streaking imprinted by far-infrared and terahertz (THz) pulses. Here, we report successful implementation of THz streaking for time stamping of an ultrashort relativistic electron beam, whose energy is several orders of magnitude higher than photoelectrons. Such an ability is especially important for MeV ultrafast electron diffraction (UED) applications, where electron beams with a few femtosecond pulse width may be obtained with longitudinal compression, while the arrival time may fluctuate at a much larger timescale. Using this laser-driven THz streaking technique, the arrival time of an ultrashort electron beam with a 6-fs (rms) pulse width has been determined with 1.5-fs (rms) accuracy. Furthermore, we have proposed and demonstrated a noninvasive method for correction of the timing jitter with femtosecond accuracy through measurement of the compressed beam energy, which may allow one to advance UED towards a sub-10-fs frontier, far beyond the approximate 100-fs (rms) jitter.

A simple and accurate HPLC-UV method was developed for the simultaneous quantitative analysis of main stilbenes and flavones in different parts (fronds, rhizomes, and frond bases) of M. struthiopteris. The chromatographic separation was performed on a Kromasil C18 column (4.6 mm × 250 mm, 5 μm) with the mobile phase of MeOH-H2O (including 0.1% phosphoric acid) using a gradient elution at the flow rate of 1.0 mL min−1 and UV detection at 295 nm. The method was validated by specificity, linearity, accuracy (recovery), and precision tests (repeatability, intra- and interday). For all the six compounds, the linear regression coefficients ranged from 0.9958 to 0.9998 within the test ranges; intra- and interday precisions were

An adequate provision of medical supplies is critical in the battle against pandemics, such as the ongoing one against COVID-19. First, this paper proposes a generalized analysis based on the fluctuation period of emergency material demand. Second, the nonlinear problem in the low-dimensional space is transformed into a linear problem in the high-dimensional feature space by using the support vector machine method, constructing a combined forecasting model of time series and support vector machines. Lastly, the daily demand of specific protective masks donated by the Wuhan COVID-19 Epidemic Prevention and Control Headquarters in the period from February 1 to March 16, 2020 is predicted through the use of data from the Wuhan Red Cross. Compared with traditional linear time series forecasting models, the proposed forecasting model sees its accuracy increased by 37.55%, with the relative errors of mean square error, average absolute error, and average absolute error percentage being respectively reduced by 37.57%, 60.88%, and 37.86%. It transpires that the ARIMA–SVM combined model is able to make full use of the potential information implied in the original data. The decision-making process provides a reference point for the forecast of the demand of medical emergency materials in future major public health emergencies. [ABSTRACT FROM AUTHOR]