In patients with resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant therapy increased the curative resection rate, disease-free survival, and overall survival for patients with ...resectable ESCC. However, the efficacy of neoadjuvant therapy varies among different patients. We aim to compare the differences in the characteristics of peripheral blood T lymphocyte subsets before and after neoadjuvant therapy in patients with different curative efficacy.
This study enrolled 266 ESCC patients who received neoadjuvant therapy and esophagectomy from August 2018 to August 2022. The postoperative pathological results divided patients into the major pathological response (MPR) and non-MPR groups. Compare the differences in peripheral blood T lymphocyte subsets and analyze the trend of changes in T lymphocyte subsets at different phases of treatment. Propensity score matching was used to reduce the influence of potential confounding factors.
Prior to the neoadjuvant therapy, particularly before the second cycle, the MPR group exhibited significantly higher ratios of CD4/CD8 (
=0.009) and helper T cells (TH ratio,
=0.030) compared to the non-MPR group. In contrast, the suppressor T cell ratio (TS ratio) was lower (
=0.016) in the MPR group. The difference in peripheral blood lymphocyte subsets between the two groups of patients who underwent neoadjuvant chemoradiotherapy is significant.
In peripheral blood, T lymphocyte subsets varied significantly based on the effectiveness of neoadjuvant treatment. Prior to the second cycle of neoadjuvant therapy, a higher CD4/CD8 and TH ratio, coupled with a decreased TS ratio, might suggest enhanced treatment outcomes.
The challenging task of analyzing on-chip power (ground) distribution networks with multimillion node complexity and beyond is key to today's large chip designs. For the first time, we show how to ...exploit recent massively parallel single-instruction multiple-thread (SIMT)-based graphics processing unit (GPU) platforms to tackle large-scale power grid analysis with promising performance. Several key enablers including GPU-speciflc algorithm design, circuit topology transformation, workload partitioning, performance tuning are embodied in our GPU-accelerated hybrid multigrid (HMD) algorithm (GpuHMD) and its implementation. We also demonstrate that using the HMD solver as a preconditioner, the conjugate gradient solver can converge much faster to the true solution with good robustness. Extensive experiments on industrial and synthetic benchmarks have shown that for DC power grid analysis using one GPU, the proposed simulation engine achieves up to 100× runtime speedup over a state-of-the-art direct solver and more than 50× speedup over the CPU based multigrid implementation, while utilizing a four-core-four-GPU system, a grid with eight million nodes can be solved within about 1 s. It is observed that the proposed approach scales favorably with the circuit complexity, at a rate about 1 s per two million nodes on a single GPU card.
Nitrative stress is a characteristic feature of the pathology of human pulmonary arterial hypertension. However, the role of nitrative stress in the pathogenesis of obliterative vascular remodelling ...and severe pulmonary arterial hypertension remains largely unclear.
Our recently identified novel mouse model (
encoding prolyl hydroxylase 2 (PHD2)) has obliterative vascular remodelling and right heart failure, making it an excellent model to use in this study to examine the role of nitrative stress in obliterative vascular remodelling.
Nitrative stress was markedly elevated whereas endothelial caveolin-1 (Cav1) expression was suppressed in the lungs of
mice. Treatment with a superoxide dismutase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride or endothelial
knockdown using endothelial cell-targeted nanoparticle delivery of CRISPR-Cas9/guide RNA plasmid DNA inhibited obliterative pulmonary vascular remodelling and attenuated severe pulmonary hypertension in
mice. Genetic restoration of Cav1 expression in
mice normalised nitrative stress, reduced pulmonary hypertension and improved right heart function.
These data suggest that suppression of Cav1 expression secondary to PHD2 deficiency augments nitrative stress through endothelial nitric oxide synthase activation, which contributes to obliterative vascular remodelling and severe pulmonary hypertension. Thus, a reactive oxygen/nitrogen species scavenger might have therapeutic potential for the inhibition of obliterative vascular remodelling and severe pulmonary arterial hypertension.
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Gating modifier toxins (GMTs) from animal venom have shown great potential in controlling blood glucose levels in type II diabetes (T2D), but their high acute toxicity and quick ...clearance in the body hamper their potential therapeutic use. Inspired by their highly positive charge, we have developed a nanocomplex system based on polyelectrolytes, in which strong interactions form between positively charged GMTs and negatively charged dextran sulfate (DS). Using melittin as a model GMT and adapting flash nanocomplexation (FNC) technology for complex preparation, uniform nanocomplexes (polydispersity index: ~0.1) with high melittin encapsulation efficiency (~100%), high payload capacity (~30%), and tunable release profiles were formulated. In contrast to the high acute liver toxicity and low survival rate (60% after 8 days) observed after a single intraperitoneal (i.p.) injection of 3 mg/kg free melittin, melittin-loaded nanocomplexes displayed improved safety (100% survival after 8 days) due to prolonged melittin release. In a mouse model of T2D, a single i.p. injection of nanocomplexes decreased the blood glucose level to 12 mmol/L within 12 h and maintained it within the therapeutic range (<15 mmol/L) for 48 h. In addition, body weight decreased following treatment. This GMT/DS binary system shows great promise due to its simple components, facile preparation method, and enhanced potential druggability, including a decreased dosing frequency, decreased acute toxicity, and improved pathological indicators.
Abstract
With the increasing penetration of distributed photovoltaic (PV) in distribution network (DN), and the randomness of PV power output, so the DN with PV is prone to voltage fluctuation or ...even overvoltage. In this paper, a double-layer distributed PV voltage control strategy is proposed. This strategy takes full advantage of reactive power of PV inverter connected to DN and aims at reducing the loss of uploading power of PV, so as to achieve collaborative control of buses voltage. It adopts the double-layer control strategy of PV system in DN, as well as the three modes switching of maximum power point tracking (MPPT), reactive power regulating and power factor regulating of PV. On the premise of realizing the effective control of buses voltage, it can reduce the loss of uploading power of PV to the greatest extent. Finally, the proposed distributed PV voltage control strategy is verified through a typical DN case based on the real time digital simulation (RTDS).
Bolted sphere joint assembly has been increasingly used in long-span spatial structures, and it is challenging to maintain good structural damage resistance of screw threaded parts subjected to ...stress concentration. In this paper, an experiment-based finite element modeling and fracture mechanical theory are applied to analyze the critical stress and stress intensity factor (SIF) for the joint assembly with crack propagation in screw threads. Accordingly, an in-plane quasi-static loading test was conducted to replicate the failure of the high-strength bolt in a bolted spherical joint. A typical fracture due to screw threads and its related fracture surface morphology is observed, and a comparison of cross-sectional strain responses is discussed. The developed finite element model is validated against experimental results in terms of moment–rotation response and the maximum stress at the root of the first internal thread of the high-strength bolt outside the junction with the screw thread. The comparison of the screw thread-related parameters for the simulation illustrates that the SIF is not sensitive to the thread root radius. Rather, the increased thread flank angle and the increased pitch are recommended for the joint assembly to achieve good fracture resistance.
At Peking University (PKU), a miniaturized 2.45 GHz antenna permanent magnet electron cyclotron resonance (PMECR) ion source, capable of generating a several-mA H+ beam, was produced and tested. The ...dimensions of the plasma chamber were ∅30 mm ×40 mm, and the entire size of the ion source (including the extraction system) supply was ∅150 mm ×160 mm. A 4.5 mA CW H+ beam was extracted at 35 kV with 200 W of microwave power supplied by a compact microwave generator with a coaxial cable. For a better understanding and optimization of the miniaturized ion source, plasma simulations were conducted to research the electromagnetic coupling of the antennas and the generation of ECR plasmas. The experimental and simulation results of the H+, H2+, and H3+ fractions of cylindrical-type and “T”-type antenna microwave ion sources were presented and compared. Based on a series of comparisons between the experimental and simulation results, the impedance of the miniaturized antenna ECR ion source plasma and the real pressure in the plasma chamber were accurately calculated. An optimized microwave coupling system was designed for the new miniaturized antenna ECR ion source. From the plasma simulation results, the transmission efficiency of microwaves increased from 32% to 89% (coupled to plasma), 15 mA H+ @ 150 W can be expected in the future.
The semisolid billets of Mg-10Gd-3Y-1Zn-0.4Zr (wt%) alloy were prepared by the strain-induced melt activation (SIMA) route, and the effects of isothermal heating parameters on the morphology and ...coarsening kinetics of primary solid grains were studied. It was found that the average grain size increased with the increase of isothermal time while the grain size showed different changing laws with the temperature at different isothermal times. The growth behavior of the primary solid grains was predominantly governed by the Ostwald ripening mechanism, although there is coalescence mechanism in some cases. As the isothermal temperature increased from 550 °C to 590 °C, the coarsening rate constant increased continuously and then declined when the temperature was further increased to 610 °C. Compared with other SIMA processed magnesium alloys, the present alloy showed a significantly lower grain coarsening rate constant due to the inhibiting effect of rare earth (RE) elements on coarsening. This research has provided an insight into the microstructural evolution of Mg-RE alloy under different heating conditions, and will provide valuable information for potential industrial applications.
•Semisolid billets of Mg-Gd-Y-Zn-Zr alloy were prepared by SIMA process.•Microstructure evolution and coarsening kinetics of primary grains were analyzed.•Coarsening rate constant of the alloy is much lower than that of other Mg alloys.•Enrichment of RE elements in liquid phase and solidification front was found.
Stem cell migration and interaction with pathology are critical to understand the complexity and status of disease recovery progress. However, the dynamic visualization still remains a great ...challenge due to imaging technical limitation, cell labeling difficulty, or blood–brain barrier (BBB). Herein, fast photoacoustic tomography (PAT) with optical molecular probes is applied to noninvasively monitor traumatic brain injury (TBI) and its rehabilitation. The vascular distribution and TBI hemorrhage are clearly imaged, longitudinally monitored, and quantified. Bone mesenchymal stem cells (BMSCs) labeled with modified Prussian blue particles (PBPs), excellent near‐infrared dyes and photoacoustic contrasts, are intravenously injected to the mice for improved observation and efficient therapy. BMSCs are demonstrated to be capable of overcoming BBB with enhanced delivery of PBPs to the brain parenchyma. Notably, the versatile BMSCs are observed by PAT to home to the damage region and repair the ruptured vasculature. Moreover, the wound treated by BMSCs exhibits much faster recovery speed than that without treatment. These findings can potentially provide a new noninvasive and high‐resolution approach to image TBI, monitor recovery process, and especially trace BMSCs. This study will stimulate extensive researches on brain diseases and provide promising strategies of dye labeled BMSCs in regenerative medicine.
Photoacoustic tomography (PAT) with optical molecular probes is applied to noninvasively monitor on‐the‐spot traumatic brain injury (TBI) and its recovery process with bone mesenchymal stem cell (BMSC) therapy. TBI hemorrhage is clearly imaged and BMSCs labeled with modified Prussian blue particles are successfully visualized in vivo by PAT. Significantly, stem cell therapy contributes to the rehabilitation of brain injury.
A triple-coil pulsed magnet aiming at 100 T (Tesla) was designed and tested at the Wuhan National High Magnetic Field Center. The magnet was powered by a 100 MJ pulse generator, a battery bank, and ...25 kV capacitor banks in combination. The magnet failed at 83 T, while the whole structure remained intact. The failure process was analyzed by using the recorded waveforms of the voltage and the current, as well as disassembling and dismantling the failed magnet. It shows that the inner coil broke down first, and then the electrical breakdown occurred between the middle and outer coils. The possible reasons were also discussed. The buckling analysis results show that the inner and middle coils would buckle at 71 T and 83 T, respectively, which were consistent with the experimental results. The cross-ply reinforcement method is proposed to enhance the structural stability of high field magnets.
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