Monocarboxylate transporter upregulation in induced regulatory T cells promotes resistance to anti-PD-1 therapy in hepatocellular carcinoma patients

BackgroundProgrammed cell death-1 (PD-1) immune checkpoint inhibitors are not effective in treating all patients with hepatocellular carcinoma (HCC), and regulatory T cells (Tregs) may determine the resistance to anti-PD-1 therapy.MethodsPatients were divided into two groups based on the clinical efficacy of anti-PD-1 therapy. Flow cytometry was used to determine the phenotype of CD4+, CD8+, and Tregs in peripheral blood mononuclear cells (PBMCs). CD4+CD45RA+T cells were sorted to analyze Treg differentiation and function.ResultsNo significant differences were found between resistant and sensitive patients in the percentage of CD4+ T cells and Tregs in PBMCs or the differentiation and function of induced Tregs (iTregs). However, iTregs from resistant patients presented higher monocarboxylate transporter (MCT) expression. Lactate induced more iTregs and improved OXPHOS levels in the resistant group. MCT1 and MCT2 were highly expressed in tumor-infiltrating Tregs, and patients with higher MCT1 expression had worse clinical outcomes. Combinatorial therapy with MCT antibody and anti-PD-1 therapy effectively inhibited tumor growth.ConclusionMCT and its downstream lactate signal in Tregs can confer anti-PD-1 resistance and may be a marker of poor prognosis in HCC

Van der Waals Heterostructure Based Field Effect Transistor Application

Van der Waals heterostructure is formed by two-dimensional materials, which applications have become hot topics and received intensive exploration for fabricating without lattice mismatch. With the sustained decrease in dimensions of field effect transistors, van der Waals heterostructure plays an important role in improving the performance of devices because of its prominent electronic and optoelectronic behavior. In this review, we discuss the process of assembling van der Waals heterostructures and thoroughly illustrate the applications based on van der Waals heterostructures. We also present recent innovation in field effect transistors and van der Waals stacks, and offer an outlook of the development in improving the performance of devices based on van der Waals heterostructures

Fatigue Performance Assessment of Composite Arch Bridge Suspenders Based on Actual Vehicle Loads

In the through arch bridges, the suspenders are the key components connecting the arch rib and the bridge deck in the middle, and their safety is an increasing focus in the field of bridge engineering. In this study, various vehicle traffic flow parameters are investigated based on the actual vehicle data acquired from the long-term structural health monitoring system of a composite arch bridge. The representative vehicle types and the probability density functions of several parameters are determined, including the gross vehicle weight, axle weight, time headway, and speed. A finite element model of the bridge structure is constructed to determine the influence line of the cable force for various suspenders. A simulated vehicle flow, generated using the Monte Carlo method, is applied on the influence lines of the target suspender to determine the stress process, and then the stress amplitude spectrum is obtained based on the statistical analysis of the stress process using the rainflow counting method. The fatigue performance levels of various suspenders are analyzed according to the Palmgren-Miner linear cumulative damage theory, which helps to manage the safety of the suspenders

Multioperation Mode Ferroelectric Channel Devices for Memory and Computation

The traditional von Neumann architecture separates memory from the central processing unit (CPU), resulting in aggravated data transfer bottlenecks between the CPU and memory during a data volume surge. Emerging technologies, such as in‐memory computing (IMC), provide a new way to overcome the limitations due to the separation of memory and computation. However, existing IMC efforts are generally limited to a single (gate‐control or drain‐control) mode of operation to achieve functionality. Herein, a 2D ferroelectric channel device that enables the feasibility of multioperation modes is proposed. In addition, rich functionalities, such as logic, nonvolatile memory, and neuromimetic plasticity modulation, by switching the operating modes are realized. A device that facilitates multimodal operations and a promising technical solution for further development of burgeoning computing architecture is provided

Permeability enhancement theory and a complete set of technology for low permeability coal seam by liquid CO2 fracturing

Liquid CO2 fracturing in low-permeability coal seams has dual gas-enhanced drainage effects of fracture reconstruction and displacement. It is a permeability enhancement technology that is easy to be used in combination with other technologies and has the potential for large-scale application. This paper proposes a theoretical system and a complete set of technical framework for fracturing and permeability enhancement of low-permeability coal seam with liquid CO2; according to the principle of stress superposition and the maximum tensile stress criterion, a model for determining the initiation pressure of liquid CO2 fracturing was established considering the change of phase state and low viscosity and strong permeability of liquid CO2 during the injection process; taking type I fracture criterion as the discriminant condition of fracture propagation, the quantitative characterizing relationship between fracturing orifice pressure and fracture propagation distance under constant fluid injection flow was established, and the influence law of fluid injection pressure, fracturing fluid viscosity and fracture occurrence on fracture propagation was clarified. On this basis, the four key parameters and their calculation methods to determine the performance of the complete set of equipment for liquid CO2 fracturing and permeability improvement in coal seam were proposed, the first complete set of equipment for underground fracturing and permeability improvement in China was developed, and the construction technology of fracturing and permeability improvement was developed, which was applied in Huainan Mining Area and Binchang Mining Area respectively

Modulating Structure Ordering via Side-Chain Engineering of Thieno[3,4-b]thiophene-Based Electron Acceptors for Efficient Organic Solar Cells with Reduced Energy Losses

Nonfullerene-based organic solar cells (OSCs) have made a huge breakthrough in the recent years. Introducing a proper side chain on the pi-conjugated backbone plays a vital role for further improving the power conversion efficiency (PCE) of OSCs due to easy tuning of the physical properties of the molecule such as absorption, energetic level, solid-state stacking, and charge transportation. More importantly, the side chain significantly affected the blend film's morphology and thus determined the PCEs of the devices. In this work, two low-band-gap nonfullerene acceptors, ATT-4 and ATT-5, with an alkyl or branched alkyl substitute on indacenodithiophene (IDT) and thieno[3,4-b]thiophene (TbT) backbone were synthesized for investigating the effect of the substituent on the performance of the nonfullerene acceptors (NFAs). In comparison to ATT-1 with p-hexylphenyl-substituted IDT and n-octyl-substituted TbT moieties, ATT-4 and ATT-5 exhibit better crystallinity with shorter interchain distance and ordered molecular structure in neat and the corresponding blend films. The tailored ATT-5 exhibits a high PCE of 12.36% with a V-oc of 0.93 V, J(sc) of 18.86 mA cm(-2), and fill factor (FF) of 0.71, blending with a wide-band-gap polymer donor PBDB-T. Remarkably, although ATT-4 and ATT-5 exhibit broader light absorption, the devices obtained higher V-oc than that of ATT-1 mainly due to the reduced nonradiative recombination in the blend films. These results implied that side-chain engineering is an efficient approach to regulate the electronic structure and molecular packing of NFAs, which can well match with polymer donor, and obtain high PCEs of the OSCs with improved V-oc, J(sc), and FF, simultaneously

Conjugation-Curtailing of Benzodithionopyran-Cored Molecular Acceptor Enables Efficient Air-Processed Small Molecule Solar Cells

Small molecule solar cells (SMSCs) lag a long way behind polymer solar cells. A key limit is the less controllable morphology of small molecule materials, which can be aggravated when incorporating anisotropic nonfullerene acceptors. To fine-tune the blending morphology within SMSCs, a pi-conjunction curtailing design is applied, which produces a efficient benzodithionopyran-cored molecular acceptor for nonfullerene SMSCs (NF-SMSCs). When blended with a molecular donor BDT3TR-SF to fabricate NF-SMSCs, the pi-conjunction curtailed molecular acceptor NBDTP-M obtains an optimal power conversion efficiency (PCE) of up to 10.23%, which is much higher than that of NBDTTP-M of longer pi-conjunction. It retains 93% of the PCE of devices fabricated in a glove box when all spin-coating and post-treating procedures are conducted in ambient air with relative humidity of 25%, which suggests the good air-processing capability of pi-conjunction curtailed molecules. Detailed X-ray scattering investigations indicate that the BDT3TR-SF:NBDTP-M blend exhibits a blend morphology featuring fine interpenetrating networks with smaller domains and higher phase purity, which results in more efficient charge generation, more balanced charge transport, and less recombination compared to the low-performance BDT3TR-SF:NBDTTP-M blend. This work provides a guideline for molecular acceptors' design toward efficient, low-cost, air-processed NF-SMSCs

Cathode interfacial layer-free all small-molecule solar cells with efficiency over 12%

While nonfullerene small-molecule solar cells (NF-SMSCs) have relatively inferior performance compared with nonfullerene polymer solar cells, their performance is improving. In this work, a weak crystalline molecular donor BSFTR, was designed and synthesized to achieve efficient NF-SMSCs. By blending with a strong crystalline acceptor NBDTP-F-out, BSFTR achieves a well-intermixed blending morphology, which favors the formation of efficient charge percolation pathways with suppressed recombination. The BSFTR:NBDTP-F-out device obtains a power-conversion efficiency (PCE) of approximately 11.97% by achieving an efficient cathode interfacial layer (CIL)-free device that delivers an even higher PCE of 12.3%, which ranks among the top values for the reported NF-SMSCs. This work provides a simple solution for achieving high-performance NF-SMSCs by identifying the key factors for designing efficient, cost-saving, mass production-favorable CIL-free organic photovoltaic devices

Monolithically integrated triaxial high-performance micro accelerometers with position-independent pure axial stressed piezoresistive beams

Abstract With the increasing demand for multidirectional vibration measurements, traditional triaxial accelerometers cannot achieve vibration measurements with high sensitivity, high natural frequency, and low cross-sensitivity simultaneously. Moreover, for piezoresistive accelerometers, achieving pure axial deformation of the piezoresistive beam can greatly improve performance, but it requires the piezoresistive beam to be located in a specific position, which inevitably makes the design more complex and limits the performance improvement. Here, a monolithically integrated triaxial high-performance accelerometer with pure axial stress piezoresistive beams was designed, fabricated, and tested. By controlling synchronous displacements at both piezoresistive beam ends, the pure axial stress states of the piezoresistive beams could be easily achieved with position independence without tedious calculations. The measurement unit for the z-axis acceleration was innovatively designed as an interlocking proof mass structure to ensure a full Wheatstone bridge for sensitivity improvement. The pure axial stress state of the piezoresistive beams and low cross-sensitivity of all three units were verified by the finite element method (FEM). The triaxial accelerometer was fabricated and tested. Results showing extremely high sensitivities (x axis: 2.43 mV/g/5 V; y axis: 2.44 mv/g/5 V; z axis: 2.41 mV/g/5 V (without amplification by signal conditioning circuit)) and high natural frequencies (x/y axes: 11.4 kHz; z-axis: 13.2 kHz) were obtained. The approach of this paper makes it simple to design and obtain high-performance piezoresistive accelerometers