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Abstract CD73, a cell surface-bound nucleotidase, serves as a crucial metabolic and immune checkpoint. Several studies have shown that CD73 is widely expressed on immune cells and plays a critical role in immune escape, cell adhesion and migration as a costimulatory molecule for T cells and a factor in adenosine production. However, recent studies have revealed that the protumour effects of CD73 are not limited to merely inhibiting the antitumour immune response. Nicotinamide adenine dinucleotide (NAD+) is a vital bioactive molecule in organisms that plays essential regulatory roles in diverse biological processes within tumours. Accumulating evidence has demonstrated that CD73 is involved in the transport and metabolism of NAD, thereby regulating tumour biological processes to promote growth and proliferation. This review provides a holistic view of CD73-regulated NAD + metabolism as a complex network and further highlights the emerging roles of CD73 as a novel target for cancer therapies.

In this study, we designed a molecularly imprinted polymers-dispersive solid-phase extraction-high-performance liquid chromatography (MIPs-DSPE-HPLC) method, as a simple and efficient platform for the sensitive detection of two sulfonamide antibiotics (SAs) of sulfamethoxine (SMM) and sulfamethoxazole (SMZ) in environmental water samples. Using SMM and SMZ as templates, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinking agent, and azodiisobutyronitrile as the catalyst, the dual-template molecularly imprinted polymers (dt-MIPs) were successfully synthesized via surface imprinting technology and multi-template imprinting strategy. The adsorption properties of the prepared MIPs were characterized, and the adsorption capacities of MIPs towards SMZ and SMM were 27.35 mg/g and 30.92 mg/g, respectively. The detection limits of the method in three environmental water samples were in the range of 0.23–1.74 μg/L, and the recoveries were between 82.7 and 110.3%, with relative standard deviations less than 5.93%. The construction process of this MIPs-DSPE-HPLC method is straightforward, exhibits high sensitivity and selectivity, and thus provides a versatile method for the quantification of SAs in complex matrices.

The rate of urbanization is increasing, and solutions to the pollution issue are desperately needed. Urban street trees are an essential factor in improving the environmental quality of cities. Quantifying precise ecological benefits of individual trees is important for monitoring urban ecology. However, since street tree surveys are time-consuming and expensive, it is challenging to assess the ecological benefits of street trees. Besides, there is still a need for more investigation into the advantages of multi-source data for ecological benefits estimates. Effective living vegetation volume (eLVV) as an urban green space indicator is beneficial for providing the vertical structure of street trees and offering a possibility for estimating the ecological benefits. The objective of this study is to evaluate the accurate ecological benefits of street trees by calculating eLVV. We developed and validated a framework for evaluating the ecological benefits of urban vegetation using point cloud and image processing techniques. Terrestrial laser scanning and unmanned aerial vehicle data were used to predict indicators at the single tree scale and road scale. Models based on game theory were applied to score all the indicators and assess the ecological benefits. The results showed that: (1) The proposed framework demonstrated that multi-source data allowed for the exact indicators of ecological benefits. (2) The eLVV of the street trees on two roads was less on the north side than on the south side, reflecting the difference in the ecology of the street trees in terms of orientation. This paper explores the advantages of multi-source data in measuring detailed ecological benefits, which support the digital management of street trees and the sustainability of regional ecology.

Gelatin-based hydrogels with excellent mechanical properties and conductivities are desirable, but their fabrication is challenging. In this work, an innovative approach for the preparation of gelatin-based conductive hydrogels is presented that improves the mechanical and conductive properties of hydrogels by integrating Z–Gln–Gly into gelatin polymers via enzymatic crosslinking. In these hydrogels (Gel–TG–ZQG), dynamic π–π stacking interactions are created by the introduction of carbobenzoxy groups, which can increase the elasticity and toughness of the hydrogel and improve the conductivity sensitivity by forming effective electronic pathways. Moreover, the mechanical properties and conductivity of the obtained hydrogel can be controlled by tuning the molar ratio of Z–Gln–Gly to the primary amino groups in gelatin. The hydrogel with the optimal mechanical properties (Gel–TG–ZQG (0.25)) exhibits a high storage modulus, compressive strength, tensile strength, and elongation at break of 7.8 MPa at 10 °C, 0.15 MPa at 80% strain, 0.343 MPa, and 218.30%, respectively. The obtained Gel–TG–ZQG (0.25) strain sensor exhibits a short response/recovery time (260.37 ms/130.02 ms) and high sensitivity (0.138 kPa−1) in small pressure ranges (0–2.3 kPa). The Gel–TG–ZQG (0.25) hydrogel-based sensors can detect full-range human activities, such as swallowing, fist clenching, knee bending and finger pressing, with high sensitivity and stability, yielding highly reproducible and repeatable sensor responses. Additionally, the Gel–TG–ZQG hydrogels are noncytotoxic. All the results demonstrate that the Gel–TG–ZQG hydrogel has potential as a biosensor for wearable devices and health-monitoring systems.

Abstract Background Delayed-onset post stroke cognitive impairment (PSCI) results from secondary neurodegeneration induced by stroke. Whereas targeted prevention or treatment strategies are still missing due to lack of evidences. This trial aims to evaluate the preventive effects of DL-3-n-butylphthalide (NBP) on delayed-onset PSCI. Methods Effects of NBP on Delayed-onset Post Stroke Cognitive Impairment (End-PSCI) is a prospective, parallel-group, open-label, multicenter, randomized controlled trial with blinded outcome assessment. Hospital patients with acute cerebral infarction (within 2 weeks of onset) will be randomized into either standard medical therapy group or standard medical therapy combined NBP treatment group (NBP 200 mg, three times per day for 24 weeks). The primary outcome is the difference of incidence of delayed-onset PSCI between two groups. The secondary outcomes include difference of white matter degeneration, cognitive scores and prevalence of early-onset PSCI between two groups. Discussion End-PSCI trial will provide evidences for NBP preventing delayed-onset PSCI. The secondary outcomes will also provide valuable insights into the pathogenesis of delayed-onset PSCI and mechanism of NBP’s actions. Trial registration Trialsearch.who.int , ChiCTR2000032555, 2020/5/2, prospectively registered.

Amino-functionalized silica@resorcinol–formaldehyde nanocomposites (NH2-SiO2@RF) were synthesized for the removal of Cr(VI) from aqueous solutions using the sol–gel technique with two simple preparation steps, including the one-pot synthesis of SiO2@RF using the Stöber method and (3-aminopropyl)triethoxysilane (APTES) modification. The morphology, particle size, functional group, and thermal stability of the obtained nanocomposites were systematically characterized, with the results indicating a uniform sphericity with a particle size of 200 nm and high thermal stability. The adsorption results demonstrated that the preferred pH value was 2, and the data were well fitted with the Langmuir and Temkin isotherm models and quasi-second-order kinetic equation, indicating a high adsorption capacity. The maximum Cr(VI) adsorption capacity from the nonlinear form of the Langmuir model was 272.6 mg·g−1. The intra-particle diffusion model accurately described the adsorption of Cr(VI) onto NH2-SiO2@RF. The changes in Gibb’s free energy, enthalpy, and entropy revealed that Cr(VI) adsorption onto NH2-SiO2@RF was a spontaneous and endothermic process. Furthermore, high selectivity was demonstrated in the material for the removal of Cr(VI) from commonly coexisting ions. The obtained nanocomposites had good regeneration properties and maintained a removal rate above 85% in the fifth adsorption–desorption experiments. Moreover, under the optimized adsorption conditions, the obtained nanocomposites were preliminarily applied to tannery wastewater, demonstrating an excellent removal effect, which indicates their potential application value.

Controlling NOx and CO2 emissions from heavy-duty diesel vehicles (HDDVs) is receiving increasing attention. Accurate measurement of HDDV NOx and CO2 emissions is the prerequisite for HDDV emission control. Vehicle emission regulations srecommend the measurement of NOx and CO2 emissions from vehicles using an emission analyzer, which is expensive and unsuitable to measure a large number of vehicles in a short time. The on-board diagnostics (OBD) data stream of HDDVs provides great convenience for calculating vehicle NOx and CO2 emissions by providing the engine fuel flow rate, NOx sensor output, and air mass flow. The calculated vehicle NOx and CO2 emissions based on the OBD data were validated by testing a heavy-duty truck’s emissions on the chassis dynamometer over the CHTC-HT driving cycle, showing that the calculated NOx and CO2 emissions based on the OBD data are consistent with the measured results by the emission analyzer. The calculated vehicle fuel consumptions based on the OBD data were close to the calculated results based on the carbon balance method and the measured results by the fuel flowmeter. The experimental results show that accessing vehicle NOx and CO2 emissions based on the OBD data is a convenient and applicable method.

The delivery system of antibiotics plays an important role in increasing the drug efficacy and reducing the risks of off-target toxicities and antibiotic resistance. The pathophysiology of bacterial infections is similar to that of tumor tissues, but only a few delivery systems have been able to target and release antibiotics on demand. Herein, we designed and developed a robust Chitosan-SS-Levofloxacin (CS-SS-LF) micelles for targeted antibiotic delivery, in which disulfide bond can be reduced by hydrogen sulfide (H2S), a typical product of Salmonella, and subsequently released antibiotic to eradicate Salmonella infection. CS-SS-LF micelles showed uniform size and sharp response to H2S. Compared with levofloxacin alone, these micelles possessed a better capacity in disrupting Salmonella biofilms and reducing bacterial burden in organs. The H2S-sensitive CS-SS-LF micelles might enable a new way to address bacterial infections.

The brown planthopper (BPH; Nilaparvata lugens) is an important pest in rice cultivation, and chemical pesticide over-use and ineffectiveness of existing Bt transgenic rice against piercing-sucking insects make novel control methods necessary. RNA interference (RNAi) biopesticide is a new type of product with high efficiency and specificity and are simple to use. The Notch signaling pathway has extensive and important physiological functions and plays a key role in the development of insects. In this study, two key ligand genes of the Notch signaling pathway, delta (dl) and jagged (jag), were selected and their lethal effects and functional analysis were systematically evaluated using a stable short-winged population (Brachypterous strain) and a long-winged population (Macropterous strain) of BPHs. The full-length coding sequences of Nldl and Nljag comprised 1,863 and 3,837 base pairs, encoding 620 and 1,278 amino acids, respectively. The nucleic acid sequences of Nldl and Nljag were identical between the two strains. The expression levels of Nldl and Nljag were relatively high in the head of the nymphs, followed by those in the abdomen. Through RNAi treatment, we found that injection of BPH nymphs of both strains with dsNldl (10–50 ng/nymph) or dsNljag (100 ng/nymph) produced lethal or teratogenic effects. dsRNA treatment showed excellent inhibitory effects on the expression of target genes on days 1 and 5, suggesting that RNAi rapidly exhibits effects which persist for long periods of time in BPHs. Taken together, our results confirm the potential of Nldl and Nljag as target genes of RNAi biopesticides, and we propose optimized dosages for the control of BPHs.

RNA interference (RNAi)-based biopesticides are novel biologic products, developed using RNAi principles. They are engineered to target genes of agricultural diseases, insects, and weeds, interfering with their target gene expression so as to hinder their growth and alleviate their damaging effects on crops. RNAi-based biopesticides are broadly classified into resistant plant-based plant-incorporated protectants (PIPs) and non-plant-incorporated protectants. PIP RNAi-based biopesticides are novel biopesticides that combine the advantages of RNAi and resistant transgenic crops. Such RNAi-based biopesticides are developed through nuclear or plastid transformation to breed resistant plants, i.e., dsRNA-expressing transgenic plants. The dsRNA of target genes is expressed in the plant cell, with pest and disease control being achieved through plant-target organism interactions. Here, we review the action mechanism and strategies of RNAi for pest management, the development of RNAi-based transgenic plant, and the current status and advantages of deploying these products for pest control, as well as the future research directions and problems in production and commercialization. Overall, this study aims to elucidate the current development status of RNAi-based biopesticides and provide guidelines for future research.

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p

BackgroundCoronary heart disease (CHD) is closely associated with cognitive impairment, especially in severe cases of heart failure. However, it is unclear whether cardiac systolic function plays a role in the relationship between pre-existing CHD and cognitive impairment in subjects without clinical heart failure.MethodsIn total, 208 subjects from the First Affiliated Hospital of Xi’an Jiaotong University were recruited from June 2014 to January 2015, and were divided into CHD (n = 118) and non-CHD (n = 90) groups according to the inclusion and exclusion criteria. The global cognitive function of all subjects was assessed by the Mini-Mental State Examination (MMSE) and cognitive impairment was defined as the score lower than the cutoff value. Left ventricular ejection fraction (LVEF) was measured using transthoracic echocardiograms. The relationship among pre-existing CHD, LVEF, and cognitive impairment was analyzed by multivariate logistic regression.ResultsIn total, 34 subjects met the criteria of cognitive impairment. Univariate analysis showed that the cognitive impairment prevalence in the CHD group was significantly higher than that in the non-CHD group (22.0 vs. 8.9%, p = 0.011). Multivariate logistic analysis revealed that CHD was significantly associated with a higher risk of cognitive impairment (odds ratio [OR] = 3.284 [95% CI, 1.032–10.450], p = 0.044) after adjusting for confounds except for LVEF. However, the OR of CHD decreased (OR = 2.127 [95% CI, 0.624–7.254], p = 0.228) when LVEF was further corrected as a continuous variable, and LVEF was negatively associated with the risk of cognitive impairment (OR = 0.928 [95% CI, 0.882–0.976], p = 0.004).ConclusionPre-existing CHD is associated with a higher risk of cognitive impairment, and such an association can be considerably explained by reduced LVEF. An impaired cardiac systolic function may play a key role in the relationship between CHD and cognitive impairment among patients with pre-heart failure conditions.

Remote sensing detection of vehicle emissions is an effective supplement to the statutory periodic inspection of in-use vehicle emissions and it is a convenient technical method for real-time screening of high-emission vehicles. The principle of remote sensing detection is to inversely calculate the absolute concentrations of gaseous pollutants in vehicle exhaust according to the relative volume concentration ratio of each exhaust component to carbon dioxide (CO2) in the vehicle exhaust plume. Because the combustion mechanisms of gasoline engines and diesel engines are different, different inversion calculation methods of remote sensing data must be applied. The absolute concentrations of gasoline vehicle gaseous emissions measured by remote sensing can be calculated by the inversion calculation method based on the theoretical air–fuel ratio combustion mechanism. However, the absolute concentrations of diesel vehicle nitrogen oxide (NOx) measured by remote sensing must be calculated by the inversion calculation method based on the correction of the excess air coefficient. For the integrated remote sensing test system of gasoline and diesel vehicles, it is necessary to determine the vehicle category according to the vehicle type and license plate and adopt different inversion calculation methods to obtain the correct remote sensing results of vehicle emissions. The big data statistical analysis method for vehicle emission remote sensing results can quickly screen high-emission vehicles and dynamically determine the remote sensing emission screening threshold of high-emission vehicles as the composition of in-use vehicles changes and the overall emission of vehicles declines, so as to achieve dynamic and accurate screening of high-emission vehicles.

Abuse and residues of antibiotics cause great harm to organisms and the environment. Appropriate sample pretreatment is usually required for sensitive determination, because of the low content presence of a variety of antibiotics in complicated matrices. Molecular-imprinting-based solid-phase extraction (MISPE) has been widely used for sample pretreatment of antibiotics, using molecularly imprinted polymers (MIPs) as adsorbents. Herein, we comprehensively review the recent advances of MISPE of antibiotics, followed by chromatographic analysis. Various solid-phase extraction (SPE) modes based on MIPs are briefly introduced, such as conventional SPE, dispersive SPE, magnetic SPE, matrix solid-phase dispersion, and pipette-tip SPE. Then, several emerging preparation techniques for antibiotics MIPs are summarized including surface imprinting, nanoimprinting, living/controlled radical polymerization, multitemplate imprinting, multifunctional monomer imprinting, and dummy template imprinting. Subsequently, applications of MISPE to analysis of a variety of antibiotics residues since 2018 are overviewed, including sulfonamides, quinolones, tetracycline, and others. Finally, the preparation and application of antibiotics MIPs are prospected.

Abstract Leather making is the process of converting raw hides into leather. Amounts of solid waste containing hazardous and high value components are generated during this process. Therefore, the elimination of the potential pollution and resource utilization of leather solid waste are the primary research hotspots. Herein, we comprehensively review the recent advances in the resource utilization of leather solid waste generated from chrome tanning including the utilization of tannery hair waste, untanned solid waste, chrome-containing leather solid waste, tannery sludge and finished leather waste, emphasizing on the general and novel utilization approaches. Finally, the remaining challenges and perspectives were summarized, in order to accelerate the development of resource utilization of leather solid waste. Graphical abstract

Mechanically enhanced gelatin-based composite hydrogels were developed in the presence of functionalized cellulose nanocrystals (CNCs) employing microbial transglutaminase (mTG) as a binding agent. In this work, the surfaces of CNCs were grafted with (3-Aminopropyl) trimethoxysilane with a NH2 functional group, and the success of CNCs’ modification was verified by FTIR spectroscopy and XPS. The higher degree of modification in CNCs resulted in more covalent cross-linking and dispersibility within the gelatin matrix; thus, the as-prepared hydrogels showed significantly improved mechanical properties and thermo-stability, as revealed by dynamic rheological analysis, uniaxial compression tests and SEM. The biocompatibility of the obtained hydrogels was evaluated by the MTT method, and it was found that the grafted CNCs had no obvious inhibitory effect on cell proliferation. Hence, the mechanically enhanced gelatin-based hydrogels might have great potential in biomedical applications.

In this study, one-dimensional (1D) zinc oxide was loaded on the surface of cobalt oxide microspheres, which were assembled by single-crystalline porous nanosheets, via a simple heteroepitaxial growth process. This elaborate structure possessed an excellent transducer function from the single-crystalline feature of Co3O4 nanosheets and the receptor function from the zinc oxide nanorods. The structure of the as-prepared hybrid was confirmed via a Scanning Electron Microscope (SEM), X-ray diffraction (XRD), and a Transmission Electron Microscope (TEM). Gas-sensing tests showed that the gas-sensing properties of the as-designed hybrid were largely improved. The response was about 161 (Ra/Rg) to 100 ppm ethanol, which is 110 and 10 times higher than that of Co3O4 (Rg/Ra = 1.47) and ZnO (Ra/Rg = 15), respectively. And the as-designed ZnO/Co3O4 hybrid also showed a high selectivity to ethanol. The superior gas-sensing properties were mainly attributed to the as-designed nanostructures that contained a super transducer function and a super receptor function. The design strategy for gas-sensing materials in this work shed a new light on the exploration of high-performance gas sensors.

In this work, hole transport layer (HTL) free bulk heterojunction organic solar cells (BHJ-OSCs) based on PTB7:PCBM as active layer have been fabricated by employing various ITO anodes with different work function. The power conversion efficiency of the BHJ-OSCs is significantly improved from 3.76 to 8.47% with increasing the work function of the ITO anode. By combining Mott–Schottky curves, external quantum efficiency and reflectance spectra of the BHJ-OSCs, we identify that the improved optoelectronic conversion due to the enhanced built-in electric field within the active layer which is induced by the high work function ITO anodes. The hole transport layer free device structure can be considered for the fabrication of cost-effective BHJ-OSCs due to their simple structure and high efficiency.

The triple helix structure of collagen can be degraded by collagenase. In this study, we explored how the intrinsic fluorescence of type I collagen was influenced by collagenase I. We found that tyrosine was the main factor that could successfully excite the collagen fluorescence. Initially, self-assembly behavior of collagen resulted in a large amount of tyrosine wrapped with collagen, which decreased the fluorescence intensity of type I collagen. After collagenase cleavage, some wrapped-tyrosine could be exposed and thereby the intrinsic fluorescence intensity of collagen increased. By observation and analysis, the influence of collagenase to intrinsic fluorescence of collagen was investigated and elaborated. Furthermore, collagenase cleavage to the special triple helix structure of collagen would result in a slight improvement of collagen thermostability, which was explained by the increasing amount of terminal peptides. These results are helpful and effective for reaction mechanism research related to collagen, which can be observed by fluorescent technology. Meantime, the reaction behaviors of both collagenase and collagenolytic proteases can also be analyzed by fluorescent technology. In conclusion, this research provides a foundation for the further investigation of collagen reactions in different areas, such as medicine, nutrition, food and agriculture.

A porcine reproductive and respiratory syndrome virus (PRRSV) QY1 was serially passed on Marc-145 cells. Virulence of different intermediate derivatives of QY1 (P5, P60, P80, and P100) were determined. The study found that QY1 had been gradually attenuated during the in vitro process. Pathogenicity study showed that pigs inoculated with QY1 P100 and P80 did not develop any significant PRRS clinic symptoms. However, mild-to-moderate clinical signs and acute HP-PRRSV symptoms of infection were observed in pigs inoculated with QY1 P60 and P5, respectively. Furthermore, we determined the whole genome sequences of these four intermediate viruses. The results showed that after 100 passages, compared to QY1 P5, a total of 32 amino acid mutations were found. Moreover, there were one nucleotide deletion and a unique 34-amino acid deletion found at 5′UTR and in nsp2 gene during the attenuation process, respectively. Such deletions were genetically stable in vivo. Following PRRSV experimental challenge, pigs inoculated with a single dose of QY1 P100 developed no significant clinic symptoms and well tolerated lethal challenge, while QY1 P80 group still developed mild fever in the clinic trial after challenge. Thus, we concluded that QY1 P100 was a promising and highly attenuated PRRSV vaccine candidate.

Homogenous advanced oxidation processes (AOPs) based on transition metal catalysts toward the activation of H2O2 to hydroxyl radical (•OH) have been widely applied to organic pollutants removal, such as Fenton and Fenton-like processes. These transition metal catalysts mostly flocculate as the pH increases. It's worth noting that the formed transition metal flocs are complex heterogeneous aggregations with active substances, providing diverse reaction spaces and interfaces. However, it is a challenge to distinguish the roles of transition metal flocs in the organic pollutants removal from homogeneous catalytic reactions. Herein, we unveiled a pathway for the long-lasting removal of organic pollutants via Cr flocs adsorbed with •OH (HO•-Cr flocs) using a stepwise method. First, adsorbed •OH (•OHads) within the HO•-Cr flocs was proved to be the active site forming hydrogen bond (H-bond) and van der Waals force with organic pollutants. Then, the presence of switchable electron transfer between Cr and OH groups within the HO•-Cr flocs was revealed, contributing to the persistent existence of •OHads and consequently ensuring the long-lasting organics removal. Further, this removal pathway of organic pollutants was confirmed during the leather wastewater treatment. These findings will complement a different pathway for organic pollutants removal via transition metal flocs and extend the lifetime of homogeneous AOPs based on transition metal catalysts, providing significant implications for their design and optimization. [ABSTRACT FROM AUTHOR]

ObjectiveTaste is one of the vital indicators for the quality evaluation of Coptis rhizome (CR), but the traditional taste evaluation lacks objectivity. By establishing the correlation between CR’s tastes and alkaloids, an objective basis for the taste evaluation was established.MethodsUltra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) and electronic tongue technique were performed to determine ten alkaloid contents and eight tastes from Coptis chinensis rhizome, Coptis deltoidea rhizome, Coptis teeta rhizome, and Coptis japonica rhizome, respectively. Combined with multivariate statistical analysis, we established models to discriminate the alkaloid contents and tastes of CR, screened the differential alkaloids and tastes, and performed Pearson’s correlation analysis on the results of alkaloids and tastes.Results1) According to the previous UHPLC-QQQ-MS/MS method established by our research group, the contents of ten alkaloids of the four species of CR were quantified, of which jatrorrhizine, columbamine, and magnoflorine were the differential alkaloids of the four species. 2) The electronic tongue technique realized the objectification of CR’s tastes and distinguished the species of CR based on the tastes of aftertaste-A, sourness, bitterness, and richness. 3) Pearson’s correlation analysis shows the bitterness of CR was mainly manifested as aftertaste-B, indicating the higher the aftertaste-B value, the higher the berberrubine content. Astringency and aftertaste-A could be suggested as quality evaluation indexes of CR, due to the positively correlated or significantly positively correlated with coptisine, epiberberine, berberine, and palmatine, respectively.ConclusionElectronic tongue technique has successfully achieved the objectification of the tastes of CR, and combined with UHPLC-QQQ-MS/MS technique for alkaloid quantification and correlation research, it provides a new idea for the quality evaluation of CR.

Introduction: Ischemic stroke is the second most common chronic disease worldwide and is associated with high morbidity and mortality. Thromboembolism and platelet aggregation are the most characteristic features of stroke. Other than aspirin, no standard, accepted, or effective treatment for acute ischemic stroke has been established. Consequently, it is essential to identify novel therapeutic compounds for this condition.Methods: In this study, novel ozagrel/paeonol-containing codrugs were synthesized and characterized using 1H-NMR, 13C-NMR, and mass spectroscopy. Their antiplatelet aggregation activity was evaluated, with compound PNC3 found to exhibit the best effect. Subsequently, studies were conducted to assess its neuroprotective effect, pharmacokinetic properties and model its binding mode to P2Y12 and TXA2, two proteins critical for platelet aggregation.Results: The results indicated that PNC3 has good bioavailability and exerts protective effects against oxygen-glucose deprivation injury in PC12 cells. Molecular docking analysis further demonstrated that the compound interacts with residues located in the active binding sites of the target proteins.Conclusion: The codrugs synthesized in this study display promising pharmacological activities and have the potential for development as an oral formulation.

Abstract Background The Veterans Affairs (VA) Healthcare System Community Hospital Transitions Program (CHTP) was implemented as a nurse-led intervention to reduce barriers that patients experience when transitioning from community hospitals to VA primary care settings. A previous analysis indicated that veterans who enrolled in CHTP received timely follow-up care and communications that improved care coordination, but did not examine cost implications for the VA. Methods A budget impact analysis used the VA (payer) perspective. CHTP implementation team members and study records identified key resources required to initially implement and run the CHTP. Statistical analysis of program participants and matched controls at two study sites was used to estimate incremental VA primary care costs per veteran. Using combined program implementation, operations, and healthcare cost estimates to guide key model assumptions, overall CHTP costs were estimated for a 5-year time horizon, including a discount rate of 3%, annual inflation of 2.5%, and a sensitivity analysis that considered two options for staffing the program at VA Medical Center (VAMC) sites. Results Implementation at two VAMCs required 3 months, including central program support and site-level onboarding, with costs of $34,094 (range: $25,355–$51,602), which included direct and indirect resource costs of personnel time, materials, space, and equipment. Subsequent annual costs to run the program at each site depended heavily on the staffing mix and caseload of veterans, with a baseline estimate of $193,802 to $264,868. Patients enrolled in CHTP had post-hospitalization VA primary care costs that were higher than matched controls. Over 5 years, CHTP sites staffed to serve 25–30 veterans per full-time equivalent transition team member per month had an estimated budget impact of $625 per veteran served if the transitional team included a medical social worker to support veterans with more social behavioral needs and less complex medical cases or $815 per veteran if nurses served all cases. Conclusions Evidence-based care coordination programs that support patients’ return to VA primary care after a community hospital stay are feasible to implement and run. Further, flexibility in staffing this type of program is increasingly relevant as the VA and other healthcare systems consider methods to reduce provider burnout, optimize staffing, reduce costs, and address other staffing challenges while improving patient care.

Abstract Background Early studies claimed that early congenital syphilitic (CS) nephropathy was rare, and systematic studies about this disease are absent, which may lead to poor awareness of early CS nephropathy in clinicians and result in misdiagnosis and poor patient prognosis. The present study systematically and comprehensively analyzes the clinical characteristics of infants with early CS nephropathy hospitalized in Beijing Ditan Hospital, an infectious disease hospital in China in order to improve the understanding and management of this disorder. Methods Data of the children with early CS from July 1, 2008, to December 31, 2021, were collected from the electronic medical record system of the hospital. Each patient’s demographic characteristics, clinical history, mother’s history of syphilitic infection, and laboratory values were extracted. The patients were enrolled to either the nephropathy group or the non-nephropathy group depending on diagnosis. Descriptive statistics was used to report basic demographics, clinical and laboratory test values, and variables were compared between the two groups by nonparametric tests, t test or χ 2 tests. Results Of the 122 children with early CS enrolled, 24(19.7%) were diagnosed with early CS nephropathy. All of the children with CS nephropathy were young infants

Fatal traffic crashes involving commercial vehicles exhibit distinct characteristics and mechanisms compared to general traffic crashes, influenced by numerous factors that impact the resulting fatalities. This study presents a comprehensive analysis of significant commercial vehicle crashes in China over a nine-year period (2014–2022), exploring an extensive range of factors including driver behavior, road conditions, vehicle characteristics, and environmental aspects. Utilizing a hierarchical Bayesian ordered probit model that incorporates both categorical and random effects, the research offers nuanced insights into the probabilistic outcomes of fatal traffic crashes. The model’s hierarchical structure enables the exploration of unobserved heterogeneities at individual and group levels. Key findings indicate that driver’s behaviors like speeding and overloading significantly escalate the likelihood of fatal traffic crashes, particularly those resulting in 10 or more fatalities. The study also highlights the role of road class in fatal crashes, with primary and secondary roads being associated with higher risks of more severe fatal crashes. The analysis extends to the impact of vehicle type, noting a distinct increase in the probabilities of fatal crashes with passenger vehicles, while freight vehicles exhibit a more complex relationship with fatal crashes severity. The insights from this study underscore the urgent need for enhanced enforcement of speed limit and vehicle weight regulations, particularly through the deployment of advanced monitoring technologies on highways frequented by commercial vehicles, and targeted infrastructure improvements on primary and secondary roads. This approach offers a novel analytical framework for evaluating commercial traffic crashes, assisting policymakers in devising targeted safety interventions to reduce the incidence of commercial vehicle crashes.

Lung cancer is a major public health challenge and, despite therapeutic improvements, is the first leading cause of cancer worldwide. The current cure rate from advanced cancer treatment is excessively low. Therefore, it is of great importance to identify novel, potent and less toxic anticancer agents for the treatment of lung cancer. The aim of our research is to synthesize a new biscoumarin 3,3'-((3,4,5-trifluorop -phenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) (C35) as an anticancer agent. C35 was simply prepared by 4-hydroxycoumarin and 3,4,5-trifluorobenzaldehyde under ethanol and its structure was analyzed by spectroscopic analyses. The anti-proliferation effect of C35 was detected using CCK-8 assay. Migration abilities were measured by Transwell assay. The expression of correlated proteins was determined by Western blot. The results showed that C35 displayed strong cytostatic effects on lung cancer cell proliferation. In addition, C35 possessed a significant inhibition of migration by reducing the expression of matrix metalloproteinases-2 (MMP-2) and MMP-9 in lung cancer cells. Furthermore, C35 treatment suppressed the phosphorylation of p38 in lung cancer cells. Moreover, in vivo experiments were carried out, in which we treated Lewis tumor-bearing C57 mice via intraperitoneal injection of C35. Results showed that C35 inhibited tumor growth in vivo. In conclusion, our study demonstrated the anticancer activity of C35 via suppression of lung cancer cell proliferation and migration, which is possibly involved with the inhibition of the p38 pathway.

Abstract Alternative computing such as stochastic computing and bio-inspired computing holds promise for overcoming the limitations of von Neumann computers. However, one difficulty in the implementation of such alternative computing is the need for a large number of random bits at the same time. To address this issue, we propose a scalable true-random-number generating scheme that we refer to as XORing shift registers (XSR). XSR generates multiple uncorrelated true random bitstreams using only two true random number generators as entropy sources and can thus be implemented by a variety of logic devices. Toward superconducting alternative computing, we implement XSR using an energy-efficient superconductor logic family, adiabatic quantum-flux-parametron (AQFP) logic. Furthermore, to demonstrate its performance, we design and observe an AQFP-based XSR circuit that generates four random bitstreams in parallel. The results of the experiment confirm that the bitstreams generated by the XSR circuit exhibit no autocorrelation and that there is no correlation between the bitstreams.

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.

Abstract. Background:. So far, there is a paucity of real-world data on the syphilis serological responses to the first-line treatment during pregnancy, and there is no relevant study on the necessity of anti-syphilis treatment during pregnancy for those patients who have been treated for syphilis before pregnancy for the prevention of mother-to-child transmission, which might provide valuable insight into treatment effectiveness and optimal management of pregnant women with syphilis. Methods:. A retrospective study on 10 years of real-world data was performed for accumulative 410 Chinese pregnant women with syphilis. The descriptive statistics were conducted in the study, and toluidine red unheated serum test (TRUST) titer responses to penicillin treatment in syphilis-infected pregnant women, and the associations with congenital syphilis were investigated. We divided the patients into two groups according to the history of anti-syphilis treatment before pregnancy (patients diagnosed with syphilis who had received anti-syphilis treatment before pregnancy, and patients screened and diagnosed with syphilis during pregnancy who had no previous history of anti-syphilis treatment). Results:. The rate of congenital syphilis in this study was 6.2% (25/406). There was no significant difference in the rate of congenital syphilis between patients who received anti-syphilis treatment before pregnancy and those who did not. Secondary syphilis and high baseline serum TRUST titer (≥1:8) in pregnant women were independent risk factors for congenital syphilis. Conclusions:. For the prevention of congenital syphilis, anti-syphilis treatment during pregnancy for syphilis seropositive pregnant women is needed, regardless of whether the patient has received anti-syphilis treatment before pregnancy, especially for those patients with secondary syphilis or high baseline serum TRUST titer, thus, timely surveillance, early diagnosis to timely treatment, and close syphilis reexamination during posttreatment follow-up, may help to reduce the above-mentioned risk factors for congenital syphilis.

Adaptive therapy is a new type of cancer treatment in which time and dose are dynamically changed according to different individuals, which is very different from conventional cancer treatment strategies that use the maximum dose to kill the tumor cells. However, how to determine the time and dose of drug treatment is a challenging problem. In this paper, a competition model between drug-sensitive cells and drug-resistant cells was established, in which pulse intervention was introduced. In addition, based on the theory of pulse optimal control, three pulse optimal control strategies are proposed in the process of cancer treatment by controlling the pulse interval and dose, minimizing the number of tumor cells at the end of the day at minimal cost. Finally, three optimization strategies were compared, using numerical simulation, in terms of tumor burden and the effect on drug-resistant cells. The results show that the hybrid control strategy has the best effect. This work would provide some new ideas for the treatment of cancer.

As a new tumor therapeutic strategy, adaptive therapy involves utilizing the competition between cancer cells to suppress the growth of drug-resistant cells, maintaining a certain tumor burden. However, it is difficult to determine the appropriate time and drug dose. In this paper, we consider the competition model between drug-sensitive cells and drug-resistant cells, propose the problem of drug concentration, and provide two state constraints: the upper limit of the maximum allowable drug concentration and the tumor burden. Using relevant theories, we propose the best treatment strategy. Through a numerical simulation and quantitative analysis, the effects of drug concentrations and different tumor burdens on treatments are studied, and the effects of cell-to-cell competitive advantage on cell changes are taken into account. The clinical dose titration method is further simulated; the results show that our therapeutic regimen can better suppress the growth of drug-resistant cells, control the tumor burden, limit drug toxicity, and extend the effective treatment time.

In this article, we mainly consider the dynamic analysis of a stochastic infectious disease model with negative feedback, a symmetric and compatible distribution family. Based on the sir epidemic model taking into account the isolation (y) and the death (v), we consider adding a new variable (w) to control the information of non-drug interventions, which measures transformations in isolation performance that determine the epidemic, and establish a new model. We have demonstrated various properties of the model solution using Lyapunov functions for this model. To begin with, we demonstrate the existence and uniqueness of the global positive solution. After that, we obtained the conditions that need to be met for the extinction of the disease and verified the correctness of the conclusion by simulating numerical values. Afterwards, we prove the stochastic boundedness and stationary distribution of the model solution.

As an important thermosetting material, flame-retardant epoxy resin has various applications in the aerospace, chemical, and electronics industry, and other fields. However, the flame retardancy of epoxy resins is often improved at the expense of mechanical performance. The contradiction between flame retardancy and mechanical properties seriously impedes the practical applications of epoxy resin (EP). Herein, iron-loaded polydopamine functionalized montmorillonite (D-Mt-Fe3+), which was prepared by dopamine, iron chloride and montmorillonite in an aqueous solution, was introduced to prepare iron-loaded polydopamine functionalized montmorillonite/epoxy resin composites (D-Mt-Fe3+/EP). As expected, D-Mt-Fe3+/EP-10 with 10 phr of D-Mt-Fe3+ passed the UL-94 V-0 rating, achieved a limiting oxygen index (LOI) value of 31.0% and reduced the smoke production rate (SPR) and total smoke production (TSP), indicating that the introduction of D-Mt-Fe3+ could endow EP with satisfactory flame retardancy through the radical scavenging function of dopamine in the gas phase and the catalytic charring effect of iron ions, respectively. Encouragingly, the mechanical property was also enhanced with the flexural strength increased by 25.5%. This work provided an attractive strategy for improving both the mechanical properties and fire resistance of EP, which greatly broadened their applications in the chemical industry and electronics field, etc.

Abstract Background An outbreak of pneumonia, COVID-19 associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and then rapidly spread to other cities. Wenzhou is located approximately 900 km from Wuhan, which was experiencing an outbreak that was severe at the time but is considered modest as the epidemic became a pandemic. We described the epidemiological characteristics of SARS-CoV-2 outside of the epicenter to help understand the transmission pattern in a mid-sized Chinese city. Methods To investigate the epidemiological and clinical characteristics of the COVID-19, we described case series of 473 patients with confirmed COVID-19 in Wenzhou, China from January 27 to March 16, 2020. We described the public health interventions of COVID-19 and evaluated the effect of interventions by the effective reproduction number (Rt). Results The median age of all patients was 47.6 years, 48.4% of whom were female. 33.8% of the patients had a history of residence in Wuhan. Fever (71.7%) and cough (43.1%) were the most common symptoms. In addition, three kinds of unconventional cases were observed, namely 4.9% asymptomatic patients, 7.6% confirmed patients who had no link to Wuhan city but contact with individuals from Wuhan without any symptoms at the time of contact, and 12.9% confirmed patients who had an unknown source of transmission. We estimated that the basic reproductive number (R0) was 2.75 (95% CI: 2.37–3.23). The Rt fluctuated within the range of 2.50 to 3.74 from January 11 to January 16 while gradually reached a peak of 3.74 on January 16. Rt gradually decreased after January 16 and decreased to 1.00 on January 30. Rt continually decreased and reached the lowest point (0.03) on February 21, 2020. Conclusion Our study presented the possibility of asymptomatic carriers affected with SARS-CoV-2, and transmission by these three kinds of unconventional patients in Wenzhou may be an important characteristic of SARS-CoV-2 transmission. The evaluation showed that a series of multifaceted interventions proved effective in controlling the epidemic of COVID-19. These findings might provide valuable examples of control policies for countries or areas in combatting the global pandemic of COVID-19.

Background and AimsThe clinical efficacy of fecal microbiota transplantation (FMT) in patients with non-alcoholic fatty liver disease (NAFLD) and the variant effects of FMT on lean and obese NAFLD patients remain elusive. Our study aimed to determine the clinical efficacy and safety of FMT for patients with NAFLD, elucidating its different influences on lean and obese patients with NAFLD.MethodsWe performed a randomized and controlled clinical trial. Patients in the non-FMT group were administered oral probiotics. In the FMT group, patients were randomized to receive FMT with donor stool (heterologous) via colonoscopy, followed by three enemas over 3 days. Both groups were also required to maintain a healthy diet and keep regular exercise for more than 40 min every day. They returned to the hospital for reexamination 1 month after treatment.ResultsFMT can decrease the fat accumulation in the liver by improving the gut microbiota dysbiosis, thus attenuating fatty liver disease. Significant differences in the clinical features and gut microbiota between lean and obese NAFLD patients were unveiled. Moreover, FMT had better effects on gut microbiota reconstruction in lean NAFLD than in obese NAFLD patients.ConclusionsFMT could successfully improve the therapeutic effects on patients with NAFLD, and its clinical efficacy was higher in lean NAFLD than in obese NAFLD patients.

In this paper, we establish a random epidemic model with double vaccination and spontaneous variation of the virus. Firstly, we prove the global existence and uniqueness of positive solutions for a stochastic epidemic model. Secondly, we prove the threshold R0* can be used to control the stochastic dynamics of the model. If R0*<0, the disease will be extinct with probability 1; whereas if R0*>0, the disease can almost certainly continue to exist, and there is a unique stable distribution. Finally, we give some numerical examples to verify our theoretical results. Most of the existing studies prove the stochastic dynamics of the model by constructing Lyapunov functions. However, the construction of a Lyapunov function of higher-order models is extremely complex, so this method is not applicable to all models. In this paper, we use the definition method suitable for more models to prove the stationary distribution. Most of the stochastic infectious disease models studied now are second-order or third-order, and cannot accurately describe infectious diseases. In order to solve this kind of problem, this paper adopts a higher price five-order model.

Quantum processors have the potential to accelerate specific computing tasks but are difficult to scale up due to engineering limitations, such as the number of available cables and cooling power for dilution refrigerators for quantum bits (qubits). Hence, it is very important to develop scalable, energy-efficient interface circuits that can control many qubits via a few control lines inside a dilution refrigerator. One of the most important interface circuits is the flux controller (FC), which generates arbitrary dc flux bias to adjust the characteristics of component devices such as qubits. In this paper, we propose and demonstrate FCs using an energy-efficient superconductor logic family, adiabatic quantum-flux-parametron (AQFP) logic. We develop two types of FCs: the AQFP FC and the AQFP/single-flux-quantum (AQFP/SFQ) FC. Both FCs require only a few control lines and have extremely small power dissipation, thus exhibiting high scalability. Furthermore, the AQFP/SFQ FC can control flux bias using ballistic SFQ transmission, which is crucial for integration with qubits. As a proof of concept, we demonstrate AQFP and AQFP/SFQ FCs at 4.2 K, fabricated by the AIST high-speed standard process. Our results indicate that AQFP logic is highly suitable for use as qubit interface circuits for very large-scale quantum processors, especially from the viewpoint of the control line count, power dissipation, and amount of supply currents.

Leaf–device interaction can effectively be modeled with a finite element model when proper finite element model parameters are applied. In order to investigate the contact mechanism of picking up sugarcane leaf during the operation of a sugarcane leaf cutting and returning machine, a geometric solid model of sugarcane leaf picking was established. A finite element numerical model to analyze the large deformation problem of flexible bodies was developed in LS-DYNA to simulate the picking process of the returning machine. A dynamic simulation of the sugarcane leaf-picking process was carried out to obtain the change of stress field and the motion posture of the sugarcane leaf and the elastic teeth. The picking process of the picking mechanism, the change in posture of the sugarcane leaves, the change in stress on the sugarcane leaf, the change in the bending angle of the sugarcane leaf and the change in stress on the elastic teeth were analyzed in detail. The results showed that the picking process can be divided into four stages: picking, lifting, pushing and retrieving. The posture changes of sugarcane leaf are “C”, logarithmic curve, wavy shape and “V”, in turn. During the picking process, the sugarcane blade showed some breakage, the sugarcane vein remained intact, and the elastic teeth did not fail. During the whole picking cycle, the maximum Von Mises stress of the blade, vein and elastic teeth were 22.8 MPa, 17.5 MPa and 900 MPa, respectively. An evaluation criterion of bending angle was creatively put forward to measure the bending deformation of leaves. The trend in the sugarcane leaf bending angle shows that it is largely variable, gradually decreasing, fluctuating and increasing with interval fluctuations. The working process of the picking mechanism was observed through a quick camera experiment. Comparing the experiment with the simulation, the changing trend of the simulation data and experimental data was generally similar. The experimental and simulation values of the average sugarcane leaf bending angle were 27° and 19°, respectively. The relative error of the average bending angle was 29.6%. It was concluded that the developed finite element model is substantial and could be applied to optimize and improve the picking mechanism. In addition, some references were provided for the contact mechanism between the picking mechanism and the sugarcane leaf.

In this paper, we study a class of predation–prey biological models with random perturbation. Firstly, the existence and uniqueness of systematic solutions can be proven according to Lipschitz conditions, and then we prove that the systematic solution exists globally. Moreover, the article discusses the long-term dynamical behavior of the model, which studies the stationary distribution and gradual properties of the system. Next, we use two different methods to give the conditions of population extinction. From what has been discussed above, we can safely draw the conclusion that our results are reasonable by using numerical simulation.

The length of a spliced pile is 2 m assembled from an original spiral pile using a connector. The whole pile is the structure of the upper straight pipe and the lower spiral. The pile–soil model is established with FEM-SPH by LS-DYNA to simulate and analyze the characteristics of the spliced piles. When the helical pile is subjected to a horizontal load, the pile rotates around the point of rotation, and the contact force position of the soil in the model is as expected. During the process of pile driving, the soil forms an inverted cone stress-area, and the maximum particle stress area near the pile tip and the ground surface is 400 Kpa, which is highly concentrated. When loaded laterally, the area of the interaction stress of the soil particles is divided into three regions: the stress effect region; the transition region; and the critical region. Then, 7° is defined as the ultimate horizontal bearing-capacity of the spliced pile, and the numerical simulation of the horizontal bearing-capacity fundamentally matches the test results. The simulation model realizes the transition from the pile installation to the lateral loading, predicts the ultimate horizontal bearing-capacity, and analyzes the stress distribution of the soil particles and the time-development of the soil displacement.

The installation of screw piles can cause damage to the soil, which is a dynamic and large deformation problem. In this paper, a FEM-SPH numerical model for the analysis of this large deformation problem was developed in LS-DYNA to simulate the installation process of screw piles. In addition, field installation tests of screw piles were carried out. By comparing the FEM-SPH simulation results with the experimental results and traditional FEM simulation results, it was found that the FEM-SPH coupling method has higher efficiency and accuracy in dealing with the large deformation problems caused by the installation of screw piles. Then, numerical simulations of screw piles with various parameters were conducted to analyze the differences in the installation process. The results show that the spiral pitch and pile diameter have a significant effect on the installation torque, soil stress and soil pressure during the installation process. During the installation process, the interaction between the screw pile and the soil is transferable. The installation of the screw pile will lead to the movement of soil particles in the radial and axial directions, resulting in heave damage to the shallow soil and cylindrical shear damage to the middle and deep soil. The influence range on the soil by the heave failure mechanism (HFM) and the cylindrical shear failure mechanism (CSFM) caused by the installation of screw piles is affected by pile parameters. The change in pile diameter will act on both HFM and CSFM, whereas the variation in spiral pitch will only have an influence on CSFM.

Background: Propolis and its preparations are components of TCM and functional food sources for antihyperlipidemia therapy. However, due to the metabolic properties of propolis, its individual components remain ambiguous, especially those that are therapeutically active. Purpose: The study presented here identified the primary target (PXR/CYP3A4) of propolis activity against hyperlipidemia and evaluated individual compounds of propolis to select a quality control marker based on this activity. Methods: Mice fed a high-fat diet were used to study the efficacy of propolis, followed by identification of substantially influenced glycolipid regulatory target(s) by propolis. Since propolis had the strongest effect on PXR expression, we took advantage of its downstream target CYP3A4, the drug metabolism activity of such enzyme is affected by alterations in PXR expression. Thus, we used the production of 1’-hydroxy-midazolam as an indicator. Compounds found by UHPLC-TOF-MS were added to a HepG2 cell solution (transfected by PXR mRNA and the CYP3A4 plasmid to simulate drug metabolism in the body) in the form of a monomer, followed by the addition of midazolam. Changes in the amount of “indicator” were used to investigate each compound's qualitative (promote or suppress) and quantitative activity. Compounds with obvious effects were quantified in propolis extract, as confirmed via Western Blot analysis regarding their PXR regulatory activity, and subjected to pharmacokinetic analysis to biter understand their metabolism in the body. Finally, components passing these screens could be regarded as quality control markers capable of indicating the efficacy of antihyperlipidemic activity via PXR/CYP3A4 regulation. Results: The use of propolis was effective in lowering TG and TC levels in mice, as well as in repairing their injured livers; its activity was comparable to the chemical and TCM positive controls. Propolis mainly suppressed PXR expression compared with other regulatory targets that were tested. Most of the individual compounds from propolis (13 out of 15) showed obvious regulatory activity of PXR/CYP3A4; however, content quantification and pharmacokinetic analyses narrowed the selection to 2 compounds, kaempferol and chrysin, as the main active components responsible for the antihyperlipidemic effect of propolis. In other words, this study suggested that propolis mainly acts on the PXR/CYP3A4 pathway to regulate glycolipid metabolism, and the 2 compounds mentioned above can be used as quality control markers (QM) to evaluate the efficacy of this activity. Conclusion: Propolis's antihyperlipidemic effect relies on its regulation of PXR/CYP3A4 expression. Kaempferol and chrysin can be regarded as QMs. In addition, the metabolite-based method for evaluating regulatory activity is much faster, more effective, and more reliable than the conventional screening method, paving the way for its future applications.

With the increasing number of automated vehicles (AVs) being tested and operating on roads, external Human–Machine Interfaces (eHMIs) are proposed to facilitate interactions between AVs and other road users. Considering the need to protect vulnerable road users, this paper addresses the issue by providing research evidence on various designs of eHMIs. Ninety participants took part in this experiment. Six sets of eHMI prototypes—Text, Arrowed (Dynamic), Text and Symbol, Symbol only, Tick and Cross and Traffic Lights, including two sub-designs (Cross and Do Not Cross)—were designed. The results showed that 65.1% of participants agreed that external communication would have a positive effect on pedestrians’ crossing decisions. Among all the prototypes, Text, and Text and Symbol, eHMIs were the most widely accepted. In particular, for elderly people and those unfamiliar with traffic rules, Text, and Text and Symbol, eHMIs would lead to faster comprehension. The results confirmed that 68.5% of participants would feel safer crossing if the eHMI had the following features: ‘Green’, ‘Text’, ‘Symbol’, or ‘Dynamic’. These features are suggested in the design of future systems. This research concluded that eHMIs have a positive effect on V2X communication and that textual eHMIs were clear to pedestrians.

Polymer-inorganic hybrid solar cells with pure vertically aligned TiO2 nanorod arrays (TiO2-NRA) normally suffer from a rather low (<0.4 V) open-circuit voltage (Voc). Recently, it has been demonstrated that the Voc in polymer/TiO2-NRA solar cells can be improved to 0.7 V by formation of homostructured core-shell structures with single-crystalline TiO2 nanorod as core and the polycrystalline TiO2 quantum dots aggregation layer as shell. However, the Voc was not achieved high enough, and effects of different crystallinity of shell on device performance have not been investigated. In this paper, we obtained three types of homostructured TiO2 core-shell nanoarrays with different crystallinity of TiO2 shell (amorphous, amorphous&crystalline, and polycrystalline) through controlling shell reaction time. The changes of device performance (in particular, the Voc) in solar cells with these arrays are studied. Results show that the device Voc gradually decreases when crystallinity of shell changes from amorphous to crystalline. Moreover, the reason for a larger Voc by amorphous shell is analyzed. More dipoles could be produced at α-TiOx shell/polymer interface than crystalline TiO2 shell/polymer interface, which results in a further up-shifting conduction band edge in TiO2 nanorod core toward the local vacuum level of the polymer, along with a further enhanced Voc. [ABSTRACT FROM AUTHOR]