Straight cylindrical stethoscopes serve as an important alternative to conventional stethoscopes, whose application in the treatment of infectious diseases might be limited by the use of protective clothing. Yet their miniaturization is challenging due to the long wavelength of low-frequency cardiac sounds. Here, we present and experimentally demonstrate an acoustic meta-stethoscope with subwavelength size, simple fabrication, and easy assembly for high-sensitivity cardiac auscultation, which simply comprises multilayered perforated round plate units and a cylindrical shell. We elucidate our proposed mechanism by analytically deducing the frequency response equation and the effective material properties of the meta-stethoscope, which proves that the equivalent acoustic propagation path is substantially increased by the metamaterial with a high refractive index, enabling downscaling the device to a subwavelength footprint. The auscultation performance of the meta-stethoscope is experimentally characterized by detecting the cardiac sound signal from the human heart through different clothing, showing an expected sensitivity enhancement exceeding 10 dB within the predicted working frequency regardless of the type of clothing. Our portable, detachable, yet effective meta-stethoscope opens a route to the metamaterial-based stethoscope research paradigm, with potential applications in diverse scenarios such as medical diagnosis and acoustic sensing.

Clouds cover two- thirds of the Earth's surface and have an important impact on the global radiation balance, global climate change, hydrological cycle, and artificial weather modification. Meanwhile,the cloud in the atmosphere remains one of the biggest uncertainties in weather and climate changes. As cloud microphysical parameters,number concentration,median volume diameter and liquid water content are important parameters to investigate cloud microphysical processes and weather prediction. In the current observation technology of cloud microphysical parameters, remote sensing method exploits the power spectrum data of satellites and radars to invert cloud microphysical parameters. However,in the progress of data inversion,properties of cloud droplets need to be assumed. Therefore, realistic droplet spectrum and cloud microphysical parameters cannot be obtained,and their measurement accuracy needs to be further verified. Airborne instrument requires strict airspace application,and its observation time,spatial continuity and sampling frequency are limited. The measurement method of existing foreign droplet spectrometer based on light scattering will destroy the original cloud droplets field distribution. In view of the above bottleneck problems,an orographic cloud observation method based on digital holographic theory is proposed. This observation method combines the active wind direction follow-up system and the nanosecond pulsed laser modulation technique based on complex programmable logic device, and utilizes global digital image fusion and local tenengrad variance algorithm. The digital holographic experimental system based on this method uses a nanosecond pulsed laser light as the light source. It can eliminate the multiple ghosting phenomenon of high-speed moving particles and obtain accurate holographic images during the recording process of holograms. In the reproduction process of holograms, global digital image fusion and local tenengrad variance algorithm can determine the focus position of particles in the measurement space to obtain more accurate three-dimensional coordinate and size of particles. For traditional fog monitor based on the light scattering theory,its sampling method is inspiratory,which causes the loss of particles during the sampling process of particles. However, the sampling method of the digital holographic experimental system is open. The active wind direction followup system can avoid particles loss to obtain the more realistic droplet spectrum. In the Liupan Mountain Orographic Cloud Field Science Experimental Base, long-term continuous observation is conducted to obtain cloud microphysical parameters. These observation data are compared and analyzed with the observation data of a light scattering-based fog monitor and forward scatter visibility instrument. In three comparative experiments, for particles of 2 similar to 4 mu m, the measurement results of the fog monitor are 61.54%,30.24% and 18.39% of the digital holographic system,respectively. For particles of 7 similar to 50 mu m, the measurement results of the fog monitor are 26.90%, 16.79% and 28.57% of digital holographic system,respectively. The above results show that the digital holographic method measures more droplets in the interval of 2 similar to 4 mu m and 7 similar to 50 mu m. In recent years,many researchers have found that FM120 has particle loss during measurement,which is consistent with the findings of this paper. This method can lay data support for improving the theoretical understanding of the physical process of cloud precipitation and the development of parametric schemes. It can also provide important technical support for research in the fields of weather,climate,artificial weather modification and atmospheric chemistry.

Background Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) may be able to have TACE through stent implantation into the portal vein with thrombosis to recover portal blood flow. Purpose The goal of this study was to compare clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular brachytherapy in HCC patients with MPVTT. Methods This study was a retrospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. Results A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times. Conclusion Endovascular implantation of brachytherapy combined with TACE is safe and effective in HCC patients with MPVTT. This combination therapy may be helpful for survival benefits to patients with stage BCLC-C HCC.

Polyethyleneimine (PEI)/silica adsorbents have been considered as a promising candidate for post-combustion CO2 capture, but the limited process study has been performed on a pilot-scale unit. Herein we report the 150 h continuous test results using a 100 kg sample of silica-PEI on a fluidized bed continuous unit. The CO2 removal efficiency and dynamic sorption capacity were evaluated continuously by changing a number of variables. For the sorption reactor, the changing variables were inlet H2O concentrations of 0-8.3 vol%, inlet CO2 concentrations of 12.0-21.5 vol%, bed temperatures of 50-70 degrees C and the bed differential pressures of 176-370 mmH(2)O. For the desorption reactor operated at the bed temperature of 129-130 degrees C, inlet H 2 O concentrations of 8.0-13.5 vol%, inlet CO2 concentrations of 14.6-81.2 vol% and bed differential pressures of 430-580 mmH(2)O were used. During continuous operation, CO2 removal efficiencies of over 90% were achieved with dynamic sorption capacities of 7.5 wt%. Solid sample collected during continuous operation were analyzed by TGA and C-13 NMR to identity the decrease of CO2 adsorption capacity and the extent of thermo-oxidative side reactions. Slow oxidative degradation of the silica-PEI occurred because the transporting adsorbent was exposure to the non-humidified air in the solid transport system.

Detecting the orders of an orbital angular momentum (OAM)-carrying beam is of fundamental interest and practical importance in wave physics. Yet accurate and fast demultiplexing of free-space OAM beams within physical space comparable to wavelength still remains challenging. Here, a passive monolayered metadecoder with compactness, high efficiency and flexibility is designed systematically and demonstrated experimentally for real-time demultiplexing of multiple OAM modes in free space. A simple yet effective mechanism of simultaneously untwisting and reshaping the synthesized vortex beams is presented to remarkably downsize the device and arbitrarily modulate the propagation path of output beam with amplified intensity and intact information, whose detection needs no sensor array or postprocessing. Consequently, the resulting device features the ultra-compact size, enhanced signal-to-noise ratio, high spectral and spatial selectivity, controllable detection locations, and furthermore, the compatibility to existing multiplexing methods. The effectiveness of proposed mechanism is demonstrated numerically and experimentally via parallel and real-time demultiplexing of a synthesized acoustic vortex using a planar metadecoder much more compact than existing devices in all three dimensions. The realization of metadecoder offers the possibility of high-capacity and miniaturized passive devices harnessing OAM and may promise important applications, including advances in high-speed underwater communication and optical on-chip signal process.

In recent years, chimeric antigen receptor T (CAR T)-cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with 89 Zr and used PET imaging in the CD19-positive and the CD19-negative K562-luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy-number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour-specific uptake was higher in the CD19-positive model than in the CD19-negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T-cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T-cell design and evaluation of solid tumour therapy.

In linear, lossless, time-invariant, and nonbiased acoustic systems, mode transitions are time reversible, consistent with Lorentz reciprocity and implying a strict symmetry in space-time for sound manipulation. Here, we overcome this fundamental limitation by implementing spatiotemporally modulated acoustic metamaterials that support nonreciprocal sound steering. Our mechanism relies on the coupling between an ultrathin membrane and external biasing electromagnetic fields, realizing programmable dynamic control of the acoustic impedance over a motionless and noiseless platform. The fast and flexible impedance modulation of our metamaterial imparts an effective unidirectional momentum in space-time to realize nonreciprocal transitions in k-ω space between different diffraction modes. On the basis of these principles, we demonstrate efficient nonreciprocal sound steering, showcasing unidirectional evanescent wave conversion and nonreciprocal upconversion focusing. More generally, our metamaterial platform offers opportunities for generation of nonreciprocal Bloch waves and extension to other domains, such as non-Hermitian topological and parity-time symmetric acoustics.

Despite the great progress achieved in nanomedicine, liquid metal (LM) nanodroplets have been mostly implemented as photo-agents for tumor phototherapy. However, in the rational design and construction of LM-based nanoplatforms for chemotherapy, limitations such as low drug-loading efficiency (LE), poor water stability, sterile and sensitive surface chemistry against ligand modification, and difficult morphology control remain to be addressed. Here, a local injectable LM-doxorubicin (LM-DOX) nanoflake-imbedded hydrogel with pH-triggered drug release is developed to achieve an enhanced therapeutic efficacy for the prevention of postoperative tumor relapse. With hyperbranched poly(amido amine) (HPAA) as the ligand, the obtained LM nanodroplets presented excellent aqueous stability and a unique flaky nanomorphology, and chemotherapeutics can be facilely conjugated via Schiff-base reaction as well. Compared to LM-based nanospheres or nanorods (LMNSs or LMNRs), LM nanoflakes (LMNFs) exhibited much higher DOX loading capacity of 63.5%. Further encapsulation of LMNFDOX within Pluronic F-127 (LMNF-DOX@Gel) was used to diminish burst drug release, achieve long-term antitumor effect, and minimize systemic toxicity. Finally, this nano-formulation was injected into the tumor resection cavity for local chemotherapy to remove the residual tumor, achieving enhanced therapeutic efficacy and biosafety than free drugs. Overall, LMNF-based hydrogel drug delivery system represents a promising candidate for postsurgical cancer treatment.

Ethnopharmacological relevance: Radix Bupleuri (RB), traditionally used to treat inflammatory disorders and infectious diseases, represents one of the most successful and widely used herbal drugs in Asia over the past 2000 years. Being realized the role in regulating metabolism and controlling Yin/Yang, RB is not only chosen specifically for treating liver meridian and the corresponding organs, but also believed to have liver meridian guiding property and help potentiate the therapeutic effects of liver. However, the ingredients in RB with liver meridian guiding property and the underly mechanism have not been comprehensively investigated. Aim of study: Considering the important role of CYP3A4 in first-pass metabolism and the liver exposure of drugs, the present study aimed to determine whether saikosaponins (SSs) and the corresponding saikogenins (SGs) have a role in inhibiting the catalytic activity of CYP3A4 in human liver microsomes and HepG2 hepatoma cells and whether they could suppress CYP3A4 expression by PXR-mediated pathways in HepG2 hepatoma cells. Materials and methods: The effect of SSs and SGs on CYP3A4-mediated midazolam1 '-hydroxylation activities in pooled human liver microsomes (HLMs) was first studied. Dose-dependent experiments were performed to obtain the half inhibit concentration (IC50) values. HepG2 cells were used to assay catalytic activity of CYP3A4, reporter function, mRNA levels, and protein expression. The inhibitory effects of SSa and SSd on CYP3A4 activity are negligible, while the corresponding SGs (SGF and SGG) have obvious inhibitory effects on CYP3A4 activity, with IC50 values of 0.45 and 1.30 mu M. The similar results were obtained from testing CYP3A4 catalytic activity in HepG2 cells, which correlated well with the suppression of the mRNA and protein levels of CYP3A4. Timedependent testing of CYP3A4 mRNA and protein levels, as well as co-transfection experiments using the CYP3A4 promoter luciferase plasmid, further confirmed that SSs and SGs could inhibit the expression of CYP3A4 at the transcription level. Furthermore, PXR protein expression decreased in a concentration- and timedependent manner after cells were exposed to SSs and SGs. PXR overexpression and RNA interference experiments further showed that SSs and SGs down-regulate the catalytic activity and expression of CYP3A4 in HepG2 may be mainly through PXR-dependent manner. Conclusion: SSs and SGs inhibit the catalytic activity and expression of CYP3A4 in a PXR-dependent manner, which may be highly related to the liver meridian guiding property of RB.

Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used 68 Ga, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by 68 Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of 89 Zr and 68 Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of 68 Ga-labeled CAR T cells is only one twenty-fourth of 89 Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of 68 Ga instead of 89 Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.

Saikosaponins (SSs) are the main active components extracted from Bupleuri Radix (BR) which has been used as an important herbal drug in Asian countries for thousands of years. It has been reported that the intestinal bacteria plays an important role in the in vivo disposal of oral SSs. Although the deglycosylated derivatives (saikogenins, SGs) of SSs metabolized by the intestinal bacteria are speculated to be the main components absorbed into the blood after oral administration of SSs, no studies have been reported on the characteristics of SGs for their intestinal absorption, and those for SSs are also limited. Therefore, a rapid UHPLC-MS/MS method was developed to investigate and compare the apparent permeability of three common SSs (SSa, SSd, SSb2) and their corresponding SGs (SGF, SGG, SGD) through a bidirectional transport experiment on Caco-2 cell monolayer model. The method was validated according to the latest FDA guidelines and applied to quantify the six analytes in transport medium samples extracted via liquid-liquid extraction (LLE). The apparent permeability coefficient (Papp) determined in this study indicated that the permeability of SGs improved to the moderate class compared to the corresponding parent compounds, predicting a higher in vivo absorption. Moreover, the efflux ratio (ER) value demonstrated an active uptake of SSd and the three SGs, while a passive diffusion of SSa and SSb2.

Abstract BackgroundThe goal of this study was to compare the clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular stent implantation with an iodine-125 seed strand in hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT).MethodsThis study was a prospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were randomly divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. The time to disease progression and survival rate were compared between the two groups.ResultsA total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p = 0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p = 0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times.ConclusionEndovascular implantation of a stent with an iodine-125 seed strand combined with TACE is safe and effective in HCC patients with MPVTT. Compared to C-TACE, D-TACE achieves more benefits regarding PFS and OS.Trial registrationThis study was a cohort study, no health-related interventions to evaluate the effects on health outcomes. This study wasn’t a clinical trial.

Radix Bupleuri (RB, Chaihu in Chinese) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Saikosaponin a (SSa), the most abundant saikosaponin in RB, exhibits various pharmacological activities, including anti-inflammatory, antitumor, antiviral, immunoregulatory, neuromodulatory, and hepatoprotective activities. A comprehensive study of the pharmacokinetic characteristics of SSa is needed to gain a detailed understanding of its pharmacodynamic mechanism. Here, we determined the effects of rat strain (Sprague Dawley and Wistar), oral dose, and cotreatment with saikosaponin b2 (SSb2) on the pharmacokinetics of SSa by measuring SSa in plasma via LC–MS/MS. The results showed that the absorption of SSa in Wistar rats was statistically superior to its absorption in Sprague Dawley rats based on pharmacokinetic parameters such as the area under the concentration–time curve (AUC0–t) and the peak concentration (Cmax). Pharmacokinetic studies of different doses of SSa in Wistar rats revealed that the systemic exposure of SSa, based on AUC values, increased disproportionately with dose, indicating that SSa exhibits non-dose-proportional pharmacokinetics. In addition, our studies showed that SSb2, a characteristic component of vinegar-baked Radix Bupleuri (VBRB), inhibits the absorption of SSa in rats. The pharmacokinetic data for SSa obtained in this study will play an important role in attempts to better understand the fate of SSa in rats and to explore how these saikosaponins are likely to exert their pharmacological effects in vivo. In addition, further research is needed to elucidate the interactions of saikosaponins with metabolic enzymes and transporters in order to account for the phenomena observed in this study.

In this study, a lab.-scale twin bubbling fluidized-bed system (TBS) has been used continuously to test the performance for CO2 adsorption of silica-PEI (S.PEI) adsorbents, containing 40 wt% of PEI, which were supplied by the University of Nottingham (UNOTT). The TBS comprises bubbling-bed adsorption and desorption reactors, a riser for pneumatic conveying of solids from the adsorption to the desorption reactor, and a cyclone for solid-gas separation. The adsorbent prepared using PEI with a molecular mass of 800 (S.PEI-0.8K) was a preliminarily tested for almost 24 h at the given operating conditions by varying the inlet sorbent/CO2 mass ratio at the adsorber to analyse the CO2 removal efficiency in the adsorption reactor and the dynamic sorption capacity of the adsorbent. A 180-h continuous test was then carried out by changing various experimental conditions such as the H2O concentration, reaction temperature, solid layer height, reaction gas flow rate, and inlet sorbent/CO2 mass ratio at the adsorber using PEI with a molecular mass of 5000 (S.PEI-5K) adsorbent. In this test, a CO2 removal efficiency of above 80% and a dynamic sorption capacity greater than 6.0 wt% were achieved.

The mesoporous silicate molecular sieve, MCM-41, has been synthesized from pulverized coal fly ash (PFA), where the silicate filtrate used is a by-product from hydrothermal zeolite production. Rice husk ash was also used for comparison but fusion with sodium hydroxide was used to prepare the silicate filtrate, along similar lines to earlier reports of using PFA as a precursor for MCM-41 synthesis. The MCM-41 samples are chemically and mineralogically similar to a commercially available sample, but with higher pore volumes dominated by mesopores (0.92-1.13 cf. 0.88 cm(3) g(-1)). After polyethyleneimine (PEI) impregnation for CO2 capture, the ash derived MCM-41 samples displayed higher uptakes than the commercial sample with the maximum achievable PEI loading of 60 Wt.% PEI (dry basis) before particle agglomeration occurs, approximately 13 compared to 11 Wt.%, respectively, the latter being comparable to earlier reports in the literature. The PFA sample that displays the fastest kinetics to achieve 90% of the equilibrium uptake had the largest mesopore volume of 1.13 cm(3) g(-1). Given the PFA-derived MCM-41 uses a waste silicate solution for hydrothermal preparation and no prior preparation is needed, production costs are estimated to be considerable lower where silicate solutions need to be prepared by base treatment, even if ash is used, as for the RHA derived MCM-41 used here.

Novel hierarchically structured microporous biocarbons with exceptionally high capacities for CO2 capture have been synthesized from the abundant agricultural waste of rice husk (RH), using a facile methodology that effectively integrated carbonization, activation, and potassium intercalation into a one-step process. Textural characterization demonstrates that the synthesized biocarbons exhibit exceedingly high ultra-microporosity accounting for up to 95% of total porosity mainly as a result of the naturally occurring silicon compounds within the RH molecular framework structures. With a modest surface area of up to 1035 m2/g and a total pore volume of 0.43 cm3/g, the best performing RH carbon has shown exceptionally high and fully reversible CO2 uptake capacity of 2.0 mmol/g at 25 °C and a CO2 partial pressure of 0.15 bar, which represents one of the highest uptakes ever reported for both carbon and MOF materials usually prepared from using cost-prohibitive precursor materials with cumbersome methodologies. It has been found that up to 50% of the total CO2 uptake is attributable to the unique surface chemistry of the RH carbons, which appears to be dominated by the enhanced formation of extra-framework potassium cations owing to the exceedingly high levels of ultra-microporosity and the presence of zeolitic structures incorporated within the carbon matrices. Characterizations by EDX element mapping, XPS, and heat of adsorption measurements confirm the existence of a range of zeolitic structures, which essentially transforms the RH carbons into a kind of zeolite-carbon nanocomposite material with strong surface affinity for CO2.