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Purpose: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer. Methods: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan–Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response. Results: We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023). Conclusion: In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. Methods: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan–Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. Results: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. Conclusion: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy. [ABSTRACT FROM AUTHOR]

Intrinsically safe solenoids drive solenoid valves in coal mining equipment. The low power consumption of these solenoids limits the response time of the solenoid valves. Additionally, the low viscosity and high susceptibility to dust contamination of the emulsion fluid often lead to leakage and sticking of hydraulic valves. This study proposes a low-power-driven, large-flux, fast-response three-stage valve structure with an internal displacement feedback device to address these issues. The critical parameters of the valve were optimized using a novel multi-objective optimization algorithm. A prototype was manufactured based on the obtained parameters and subjected to simulation and experimental verification. The results demonstrate that the valve has an opening time of 21 ms, a closing time of 12 ms, and a maximum flow rate of approximately 225 L/min. The driving power of this structure is less than 1.2 W. By utilizing this valve for hydraulic cylinder control, a positioning accuracy of ± 0.15 mm was achieved. The comparative test results show that the proposed structural control error fluctuation is smaller than that of the 3/4 proportional valve. [ABSTRACT FROM AUTHOR]

Recent advancements in offline reinforcement learning (offline RL) have leveraged the Q-ensemble approach to derive optimal policies from static datasets collected in the past. By increasing the batch size, a portion of Q-ensemble instances penalizing out-of-distribution (OOD) data can be replaced, significantly reducing the Q-ensemble size while maintaining comparable performance and expediting the algorithm's training. To further enhance the Q-ensembles' ability to penalize OOD data, a technique involving large batch punishment and a binary classification network was employed. This method differentiates in-distribution (ID) data from OOD data. For ID data, positive adjustments to Q values were made (reward-based adjustment), whereas negative adjustments (penalty-based adjustment) were applied for OOD data, which replaced some OOD data punishment within large Q-ensembles, reducing their size without compromising performance. For different tasks on the D4RL benchmark datasets, we selectively use one of its methods. Experimental results demonstrated that employing reward-based adjustment improved algorithm performance. Simultaneously, utilizing penalty-based adjustment reduced Q-ensemble size without compromising performance. In comparison to LB-SAC, this approach reduced average convergence time by 38% for datasets utilizing penalty-based adjustment, thanks to the introduction of a simpler binary classification network and a reduced number of Q networks. [ABSTRACT FROM AUTHOR]

Background: The efficacy of afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after afatinib progression has yet to be determined. Method: Patients with HER2 mutated advanced lung adenocarcinoma administered afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on afatinib. Survival curves were plotted with the Kaplan–Meier method. A swimming plot was used to describe the specific treatments. Additionally, patient-derived tumor organoids (PDTOs) were established from HER2-amplified NSCLC patient samples to investigate the antitumor activity of pyrotinib in HER2-amplified tumor cells in vitro. Results: A total of 99 patients were enrolled, 13 of whom were administered pyrotinib after progression on afatinib. No statistical difference in PFS of pyrotinib was observed between patients whether be treated after afatinib progression or not (6.7 months vs. 4.4 months, P = 0.817), thus indicating that progression on afatinib did not affect the efficacy of pyrotinib. Further analysis was conducted on the former patients, which comprising eight patients administered interval chemotherapy after progression on afatinib. Two patients achieved PR after pyrotinib treatment. No independent factors were found to influence the PFS of pyrotinib. PDTOs confirmed the anti-tumor activity of pyrotinib in NSCLC tumor cells with HER2 amplification. Conclusions: Progression after prior afatinib treatment does not influence the efficacy of pyrotinib treatment. Pyrotinib may be a salvage option for patients with HER2 mutation who have experienced progression on afatinib. [ABSTRACT FROM AUTHOR]

Royal Jelly (RJ) is a natural substance produced by honeybees, serving not only as nutrition for bee brood and queens but also as a functional food due to its health-promoting properties. Despite its well-known broad-spectrum antibacterial activity, the precise molecular mechanism underlying its antibacterial action has remained elusive. In this study, we investigated the impact of RJ on the bacteria model MG1655 at its half-maximal inhibitory concentration, employing LC–MS/MS to analyze proteomic changes. The differentially expressed proteins were found to primarily contribute to the suppression of gene expression processes, specifically transcription and translation, disrupting nutrition and energy metabolism, and inducing oxidative stress. Notably, RJ treatment led to a marked inhibition of superoxide dismutase and catalase activities, resulting in heightened oxidative damage and lipid peroxidation. Furthermore, through a protein–protein interaction network analysis using the STRING database, we identified CRP and IHF as crucial host regulators responsive to RJ. These regulators were found to play a pivotal role in suppressing essential hub genes associated with energy production and antioxidant capabilities. Our findings significantly contribute to the understanding of RJ's antibacterial mechanism, highlighting its potential as a natural alternative to conventional antibiotics. The identification of CRP and IHF as central players highlights the intricate regulatory networks involved in RJ's action, offering new targets for developing innovative antimicrobial strategies. [ABSTRACT FROM AUTHOR]

In this paper, aiming at the phenomenon that the dead zone and hysteresis of three-way proportional pressure reducing valve (TPPRV) will seriously affect the control accuracy of construction machinery, a polynomial excitation current compensation controller (PECC) is designed, which is novel and easy to realize in engineering. Firstly, the mathematical model of TPPRV is established, and the dead zone and hysteresis of TPPRV are quantitatively analyzed by using the performance test platform of proportional pressure reducing valve. Secondly, the design principle of PECC is expounded, and the controller model is deduced theoretically. The proposed PECC has two main advantages. One is that the method does not need to establish the nonlinear model of dead zone and hysteresis, and the other is that the method can compensate the dead zone and hysteresis simultaneously. Finally, the compensation control performance of PECC is verified by using the performance test platform of proportional pressure reducing valve. The experimental results show that PECC can greatly reduce the adverse effects of dead zone and hysteresis on TPPRV, and has great applicability under different working conditions. Relevant research results can significantly improve the proportional control accuracy of TPPRV, which has a certain engineering value. [ABSTRACT FROM AUTHOR]

Background: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear. Method: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan–Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions. Results: A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1 months vs. 2.5 months, P < 0.001; iPFS: 8.1 months vs. 2.5 months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1 months vs. 1.9 months, P = 0.001; iPFS: 8.1 months vs. 1.9 months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4 months vs. 2.1 months, P < 0.001; iPFS: 9.2 months vs. 2.1 months, P = 0.002). No new or severe adverse events were observed with combination therapy. Conclusion: The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs. [ABSTRACT FROM AUTHOR]

In-situ chemical oxidation (ISCO) has been widely utilized for the remediation of organic contaminated soil, while the long-term remediation efficiency and mechanism have been rarely explored, which is of great importance to the field implementation due to the potential for secondary pollution in later stages after remediation. The geotechnical centrifuge has proven to be a reliable tool for simulating long-term geoenvironmental issues. Nevertheless, its application in oxidative remediation has been hindered by the lack of suitable apparatus and scaling principles. For this purpose, a series of centrifuge model tests are comprehensively designed and performed in this study. A comprehensive analysis was carried out to evaluate the long-term effectiveness of the site remediation. The investigation focused on analyzing the transport mechanisms of contaminants and secondary contaminants at various time scales (7 and 10 years) and spatial scales. The results of the modeling of model tests indicate that simulating chemical oxidation processes in the centrifuge is feasible with a Damoner number above 100. The model effectively represents the target contaminant (diesel) removal rate and the remaining diesel concentration at 10 years was significantly lower and more uniform than that at 7 years, with a removal rate of approximately 64%. The variation in the secondary pollutants (SO42−) was more complicated, as its generation and migration are influenced by multiple processes and pH values. The diesel concentrations meet permitted values at 7 and 10 years while further remediation is needed for residual SO42−. The remediation process lowers soil pH by 2, shifting it from neutral to acidic. The centrifuge model offers substantial data support for the evaluation of long-term remediation effectiveness at contaminated sites. [ABSTRACT FROM AUTHOR]

Direct solar-to-hydrogen conversion from pure water using all-organic heterogeneous catalysts remains elusive. The challenges are twofold: (i) full-band low-frequent photons in the solar spectrum cannot be harnessed into a unified S1 excited state for water-splitting based on the common Kasha-allowed S0 → S1 excitation; (ii) the H+ → H2 evolution suffers the high overpotential on pristine organic surfaces. Here, we report an organic molecular crystal nanobelt through the self-assembly of spin-one open-shell perylene diimide diradical anions (:PDI2-) and their tautomeric spin-zero closed-shell quinoid isomers (PDI2-). The self-assembled :PDI2-/PDI2- crystal nanobelt alters the spin-dependent excitation evolution, leading to spin-allowed S0S1 → 1(TT) → T1 + T1 singlet fission under visible-light (420 nm~700 nm) and a spin-forbidden S0 → T1 transition under near-infrared (700 nm~1100 nm) within spin-hybrid chromophores. With a triplet-triplet annihilation upconversion, a newly formed S1 excited state on the diradical-quinoid hybrid induces the H+ reduction through a favorable hydrophilic diradical-mediated electron transfer, which enables simultaneous H2 and O2 production from pure water with an average apparent quantum yield over 1.5% under the visible to near-infrared solar spectrum. Achieving direct solar-to-hydrogen conversion from pure water using solely organic heterogeneous catalysts is still challenging. Here the authors report an all-organic semiconductor catalyst system for overall water splitting under visible to near-infrared light via triplet-triplet annihilation up conversion based on spin coupling. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) materials that combine ferromagnetic, semiconductor, and piezoelectric properties hold significant potential for both fundamental research and spin electronic devices. However, the majority of reported 2D ferromagnetic-semiconductor-piezoelectric materials rely on d-electron systems, which limits their practical applications due to a Curie temperature lower than room temperature (RT). Here, we report a high-crystallinity carbon nitride (CCN) material based on sp-electrons using a chemical vapor deposition strategy. CCN exhibits a band gap of 1.8 eV and has been confirmed to possess substantial in-plane and out-of-plane piezoelectricity. Moreover, we acquired clear evidences of ferromagnetic behavior at room temperature. Extensive structural characterizations combined with theoretical calculations reveal that incorporating structural oxygen into the highly ordered heptazine structure causes partial substitution of nitrogen sites, which is primarily responsible for generating room-temperature ferromagnetism and piezoelectricity. As a result, the strain in wrinkles can effectively modulate the domain behavior and piezoelectric potential at room temperature. The addition of RT ferromagnetic-semiconductor-piezoelectric material based on sp-electrons to the family of two-dimensional materials opens up numerous possibilities for novel applications in fundamental research and spin electronic devices. [ABSTRACT FROM AUTHOR]

Spiking neural network (SNN) is a biologically-plausible model and exhibits advantages of high computational capability and low power consumption. While the training of deep SNN is still an open problem, which limits the real-world applications of deep SNN. Here we propose a deep SNN architecture named Spiking SiamFC++ for object tracking with end-to-end direct training. Specifically, the AlexNet network is extended in the time domain to extract the feature, and the surrogate gradient function is adopted to realize direct supervised training of the deep SNN. To examine the performance of the Spiking SiamFC++, several tracking benchmarks including OTB2013, OTB2015, VOT2015, VOT2016, and UAV123 are considered. It is found that, the precision loss is small compared with the original SiamFC++. Compared with the existing SNN-based target tracker, e.g., the SiamSNN, the precision (success) of the proposed Spiking SiamFC++ reaches 0.861 (0.644), which is much higher than that of 0.528 (0.443) achieved by the SiamSNN. To our best knowledge, the performance of the Spiking SiamFC++ outperforms the existing state-of-the-art approaches in SNN-based object tracking, which provides a novel path for SNN application in the field of target tracking. This work may further promote the development of SNN algorithms and neuromorphic chips. [ABSTRACT FROM AUTHOR]

Urapidil is an important drug for the treatment of essential hypertension and intravenously in hypertensive emergencies. Herein, an improved route to Urapidil was introduced. The new designed synthetic route starts with the addition reaction of 1-(2-methoxyphenyl)piperazine and oxetane catalyzed by Yb(OTf)3 in acetonitrile to form the key intermediate 3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-1-ol. Additionally, 3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-1-ol was purified by recrystallization from the optimized solvents, which was beneficial to large scale production. Intermediate 3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl-4-methylbenzenesulfonate was cast directly for the subsequent reaction without further purification. The overall yield of this route is about 45%. The structure of the final product was well confirmed by 1H-NMR, 13C-NMR and HRMS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). Methods: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. Results: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. Conclusion: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331). [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) – in which the current flows perpendicularly to the substrate surface direction – are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.2D vertical transport transistors (VTFETs) may promote the downscaling of electronic devices, but their performance is usually restricted by the thermionic limit. Here, the authors report the realization of short-channel steep-slope VTFETs based on MoS2/MoTe2 heterojunctions integrated with resistance threshold switching cells. [ABSTRACT FROM AUTHOR]

To systematically investigate the effect of GaN interlayers (IL) on electron transport properties of GaN-based heterostructures, three groups of heterostructures, AlInN/AlN/GaN/InGaN/GaN, AlInN/GaN/AlN/InGaN/GaN and AlInN/AlGaN/GaN/InGaN/GaN were compared in this study, noted as AlN-IL first, GaN-IL first and AlGaN-IL first, respectively. The conduction band diagram and electron density were simulated with a numerical method, and the mobility was calculated analytically with seven scattering mechanisms. Compared with the heterostructure without GaN-IL, an increased thickness of GaN-IL leads to a greater dispersion of electrons into the upper GaN channel. Consequently, the density and mobility of the two-dimensional electron gas (2DEG) result from combined contributions from both the upper GaN and lower InGaN channels. After analyzing the scattering mechanism and electron distribution probability in each channel, the study explores variations in GaN-IL thickness, temperature, and alloy composition in AlGaN IL. The results show that almost all mobilities are enhanced with the incorporation of GaN-IL even at an elevated temperature of 1000 K, especially for AlN-IL first and AlGaN-IL first structure. The mobility of all heterostructures in the GaN channel is primarily reduced by alloy composition fluctuation scattering and polar optical phonon scattering. Conversely, alloy disorder scattering and polar optical phonon scattering should be minimized in the InGaN channel. [ABSTRACT FROM AUTHOR]

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of the P23-45 RNAPs with other RNAPs suggest that, despite the extensive functional differences, the two P23-45 RNAPs originate from an ancient gene duplication in an ancestral phage. Our findings demonstrate striking adaptability of RNAPs that can be attained within a single virus species. The authors describe the structure and function of two evolutionarily diverged RNA polymerases of a thermophilic phage. One of the polymerases is fused to the phage tape measure protein, a virion component dictating the length of the phage tail. [ABSTRACT FROM AUTHOR]

Network-assisted full-duplex (NAFD) cell-free distributed massive multiple-input multiple-output (MIMO) systems enable uplink (UL) and downlink (DL) communications within the same time-frequency resources, which potentially reduce latency by avoiding the overhead of switching UL/DL modes. However, how to choose UL/DL modes remains an important factor affecting system performance. With the dramatic increase in the number of users and access points (APs), massive access brings significant overhead in the mode selection. Additionally, the different quality of service (QoS) among users also makes the effective utilization of resources difficult. As one of the most promising technologies in sixth-generation (6G), network slicing enables the adaptive configuration of limited UL/DL resources through the resource isolation assisted NAFD technique. Therefore, we propose a slicing capacity-centered scheme. Under this scheme, APs are motivated by slicing requirements and associated slices to form different subsystems. Collaborative mode selection and resource allocation are performed within each subsystem to reduce overhead and improve resource utilization. To implement this scheme efficiently, a double-layer deep reinforcement learning (DRL) mechanism is used to realize the joint optimization of mode selection and resource allocation. Simulation results show that the slicing capacity-centered scheme can effectively improve resource utilization and reduce overhead. [ABSTRACT FROM AUTHOR]

Purpose: Drug resistance inevitably occurs despite the encouraging results of immunotherapy. This study attempted to investigate immunotherapy rechallenge treatment regimens and factors associated with outcomes in patients with non-small cell lung cancer (NSCLC) according to resistance status. Methods: A retrospective study was conducted on patients with advanced NSCLC who received immune checkpoint inhibitor (ICI) monotherapy and immune rechallenge between March 2016 and December 2022. Primary resistance (RR) was defined by an absence of response after treatment administered for less than 6 months before progression. Acquired resistance (AR) was defined as a response to immunotherapy treatment administered for more than 6 months before progression. Disease progression in as many as three lesions was defined as systemic progression, whereas disease progression in fewer than three lesions was defined as oligo-progression. Results: Of 40 patients, 18 (45%) had primary resistance, and 22 (55%) developed AR. Overall survival (OS) was not reached. A significant difference in progression-free survival (PFS) was observed in individuals rechallenged with ICIs after AR and RR (7.0 months vs. 2.1 months, P = 0.003). Patients receiving interval treatment before rechallenge achieved longer PFS than those who did not (6.2 months vs. 4.0 months, P = 0.027). Multivariate analysis demonstrated that systemic progression was a risk factor significantly associated with PFS after ICI rechallenge (P = 0.006). After AR, ICI rechallenge prolonged the duration of PFS if patients developed oligo-progression (5.4 months vs. 1.1 months, P < 0.001). Conclusion: ICI rechallenge is likely to be an option for patients with oligo-progression during rechallenge, particularly after AR. [ABSTRACT FROM AUTHOR]

Hydraulically fractured well productivity greatly depends on fracture conductivity, which itself is dictated by proppant transport and placement. To guide engineering design and evaluate performance of proppant placement, a full understanding of the underlying physics and robust numerical models are needed. This paper introduces a continuum approach for simulating the transport of multiple fluids and proppant particles within hydraulic fractures. To achieve computational efficiency, this proppant model is developed based on the assumption of multi-component single phase flow and captures proppant settling, hindering effects, proppant-bed erosion and transport. Inter-particle stresses and collisions are not numerically calculated but represented through empirical correlations to include the effects of particle clustering and hindered settling. This model couples the fluid phase and particle phase through the slip velocity, which is governed by particle settling, particle–particle interaction and fluid-particle drag forces. The presented proppant model is validated by comparing numerical results with experimental data. With the calibrated simulation, the modeling capabilities on fracturing treatment design are demonstrated through sensitivity analysis and field-scale applications. Moreover, based on proppant placement and deformation, a generic model is applied to forecast fracture conductivity in different scenarios. As illustrated in this study, this coupled three-dimensional model is capable of simulating proppant placement and fracture conductivity under various operational conditions. This model can be broadly applied to improve fracturing design in various formations, including tight sandstone, shale, coal bed methane and carbonate reservoirs. Highlights: To achieve computational efficiency, we introduce a continuum approach for simulating the transport of multiple fluids and proppant particles. In this new model, several underlying mechanisms are considered to highlight the coupling between proppant transport and fluid flow. The modelling predictions on proppant transport and distribution show a good agreement with the reported experimental data. Using the model calibrated to lab tests, the modeling capability is demonstrated and controlling parameters on proppant transport are identified. This model works for field-scale hydraulic fracturing simulations to model proppant transport and fracture conductivity evolution. [ABSTRACT FROM AUTHOR]

Computational thinking (CT) skills of pre-service teachers have been explored extensively, but the effectiveness of CT training has yielded mixed results in previous studies. Thus, it is necessary to identify patterns in the relationships between predictors of CT and CT skills to further support CT development. This study developed an online CT training environment as well as compared and contrasted the predictive capacity of four supervised machine learning algorithms in classifying the CT skills of pre-service teachers using log data and survey data. First, the results show that Decision Tree outperformed K-Nearest Neighbors, Logistic Regression, and Naive Bayes in predicting pre-service teachers' CT skills. Second, the participants' time spent on CT training, prior CT skills, and perceptions of difficulty regarding the learning content were the top three important predictors in this model. [ABSTRACT FROM AUTHOR]

Conclusions: We have proposed and theoretically analyzed an electro-tunable extreme Huygens’ BIC metasurface consisting of LiNbO3 elliptical cylinders. After optimizing the geometry parameter of the structure, we have realized over 2π phase retardation of transmitted light while maintaining over 96% transmission amplitude. The metasurface can be continuously tuned based on the EO property of the LiNbO3 without a drastic change in the transmission. The proposed LiNbO3 metasurface will be a good candidate for developing reconfigurable optical components in optical wavefront shaping, displaying, and other applications. [ABSTRACT FROM AUTHOR]

Conclusion: A MoS2 channel FeFET with a P–Si gate was developed for use as a photosensor with a memory function. A current ratio of 104 was achieved at an irradiation power of 20 nW. The reliability of the device was evaluated by means of endurance tests, and a retention time of more than 1000 s was observed. Furthermore, in-sensor digital computing was verified by applying an optoelectronic hybrid logic AND gate. This novel optical sensing principle enables the development of new approaches for optoelectronic hybrid integration. [ABSTRACT FROM AUTHOR]

Highlights: Convincing candidates of flexible (stretchable/compressible) electromagnetic interference shielding nanocomposites are discussed in detail from the views of fabrication, mechanical elasticity and shielding performance. Detailed summary of the relationship between deformation of materials and electromagnetic shielding performance. The future directions and challenges in developing flexible (particularly elastic) shielding nanocomposites are highlighted. With the extensive use of electronic communication technology in integrated circuit systems and wearable devices, electromagnetic interference (EMI) has increased dramatically. The shortcomings of conventional rigid EMI shielding materials include high brittleness, poor comfort, and unsuitability for conforming and deformable applications. Hitherto, flexible (particularly elastic) nanocomposites have attracted enormous interest due to their excellent deformability. However, the current flexible shielding nanocomposites present low mechanical stability and resilience, relatively poor EMI shielding performance, and limited multifunctionality. Herein, the advances in low-dimensional EMI shielding nanomaterials-based elastomers are outlined and a selection of the most remarkable examples is discussed. And the corresponding modification strategies and deformability performance are summarized. Finally, expectations for this quickly increasing sector are discussed, as well as future challenges. [ABSTRACT FROM AUTHOR]

Invasive mucinous adenocarcinoma (IMA) is a rare variant of adenocarcinoma with unique clinical, radiological, and pathological features, among which KRAS mutation is the most common. However, the differences in the efficacy of immunotherapy between KRAS-positive IMA and invasive non-mucinous adenocarcinoma (INMA) patients remain unclear. Patients with KRAS mutated adenocarcinomas receiving immunotherapy between June 2016 and December 2022 were enrolled. Based on mucin-producing status, the patients were placed into two subgroups: the IMA group and INMA group. Patients with IMA were further classified into two subtypes according to the presence of mucin patterns: pure IMA (≥ 90%) and mixed mucinous/nonmucinous adenocarcinoma (≥ 10% of each histological component). Kaplan–Meier Curves and log-rank tests were used to analyze survival. Cox regression analysis of PFS were used to analyze the independent factors associated with efficacy. Sixty-five advanced adenocarcinoma patients with KRAS mutations received immunotherapy, including 24 patients with IMA and 41 with INMA. The median progression-free survival (PFS) was 7.7 months, whereas the median overall survival (OS) was 24.0 months. Significant difference in PFS could be observed in IMA and INMA (3.5 months vs. 8.9 months; P = 0.047). Patients with pure IMA tended toward prolonger survival in contrast to mixed mucinous/nonmucinous adenocarcinoma in PFS (8.4 months vs. 2.3 months; P = 0.349). The multivariable analysis demonstrated that IMA was an independent risk factor for PFS. In KRAS mutated patients, IMA was associated with poorer PFS after immunotherapy compared with INMA. [ABSTRACT FROM AUTHOR]

The underwater robot (UR) is an embodiment of interdisciplinary technologies, integrating underwater communication, machinery, marine science, computer science, and robotics. Although URs enable a highly engaging and exploratory construction that can foster children's engineering education and ocean literacy, little work has explored UR design and education for children. In this paper, we present a study using URs to engage children in exploring engineering, robotics, environmental science, and marine sustainability. We introduce ModBot, a modular UR-making toolkit for children that uses hardware blocks and software applications for UR creation. We describe a study with 31 children (ages 5–8; 16 girls and 15 boys) and report how they learned UR concepts such as buoyancy and balance through playing with the ModBot kit and creating their own URs. This study is intended to investigate how URs can be used to spark children's interest in water environments and make a connection to robotics by the creation of their own URs. [ABSTRACT FROM AUTHOR]

Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABAARs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABAARs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABAARs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1α/Neurexin surface delivery. Together, MADD-4B and NRX-1α recruit postsynaptic NLG-1/Neuroligin and stabilize GABAARs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABAARs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1α, which act as anterograde signals to recruit postsynaptic GABAARs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity. The pre-and postsynaptic communication is critical for faithful synaptic transmission and induction of synaptic plasticity. Here, the authors found that CaMKII functions at GABAergic neurons to recruit GABAARs by triggering anterograde signals. [ABSTRACT FROM AUTHOR]

Synthesized β-Ga2O3 nanobelts have excellent electrical and optical properties. However, their widths are mostly limited to only a few microns or even tens of nanometers by far, which presents the big challenge for the fabrication of nanodevices and nanosensors. In this work, the β-Ga2O3 single crystal nanobelts synthesized by carbothermal reduction have the ultra-large widths which can reach up to 145 μm. Schottky barrier diode based on the nanobelt shows the impressive UV-induced rectifying characteristics due to ultra-low dark current of 100–200 fA at forward bias. At 5 V and 15 V, its ratios of current under 254 nm UV condition and that under dark condition are as high as 5 × 105 and 1.4 × 106, respectively. Meanwhile, the diode also has the high breakdown voltage of 240 V. [ABSTRACT FROM AUTHOR]

Background: Thymic carcinoma (TC) is a rare type of a malignant tumor. The optimal treatment for Masaoka–Koga stage IVB TC patients is controversial due to the rarity of the disease. Chemotherapy is still the preferred option, but the outcomes are unsatisfactory. Whether radiotherapy combined with chemotherapy could improve prognosis remains unclear. Methods: Untreated stage IVB TC patients who have received first-line chemotherapy were included in the present study. The patients who have undergone surgery were excluded. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). Results: Sixty-seven patients were included in the study. A total of 31 patients received chemoradiotherapy (ChemoRT cohort), and the remaining 36 patients only received chemotherapy (Chemo cohort). The median follow-up period was 40.3 months. The ORR for the ChemoRT and Chemo cohorts was 61.3 and 27.8%, respectively (P = 0.006). Furthermore, PFS (P = 0.003) and OS (P = 0.046) were significantly superior in the ChemoRT cohort. Radiotherapy maintained a significant favorable effect on PFS in multivariate analysis (P = 0.014), but the effect on OS was insignificant (P = 0.249). There was no advantage in PFS (P = 0.302) in the ChemoRT cohort in patients who received < 4 cycles of chemotherapy. In contrast, radiotherapy significantly improved PFS (P = 0.005) in patients who received ≥ 4 cycles of chemotherapy. Conclusions: Chemoradiotherapy used as the first-line treatment improved ORR and PFS in Masaoka–Koga stage IVB TC patients. Patients receiving more cycles of chemotherapy may have a better chance to benefit from chemoradiotherapy. [ABSTRACT FROM AUTHOR]

This study theoretically demonstrated the oxygen vacancy (VO2+)-based modulation of a tunneling junction memristor (TJM) with a high and tunable tunneling electroresistance (TER) ratio. The tunneling barrier height and width are modulated by the VO2+-related dipoles, and the ON and OFF-state of the device are achieved by the accumulation of VO2+ and negative charges near the semiconductor electrode, respectively. Furthemore, the TER ratio of TJMs can be tuned by varying the density of the ion dipoles (Ndipole), thicknesses of ferroelectric-like film (TFE) and SiO2 (Tox), doping concentration (Nd) of the semiconductor electrode, and the workfunction of the top electrode (TE). An optimized TER ratio can be achieved with high oxygen vacancy density, relatively thick TFE, thin Tox, small Nd, and moderate TE workfunction. [ABSTRACT FROM AUTHOR]

A study of 1.7 kV normally-off p-GaN gate high-electron-mobility transistors (HEMTs) on SiC substrates is presented. The fabricated p-GaN HEMT with a gate-drain spacing LGD = 5 µm exhibited a threshold voltage of 1.10 V, a maximum drain current of 235 mA/mm, an ON/OFF ratio of 108, and a breakdown voltage of 440 V. Benefiting from the semi-insulating and high-critical-electric-field substrate, the p-GaN HEMT with LGD = 23 µm achieved the remarkably high breakdown voltage of 1740 V with substrate grounded. This breakdown voltage is very high compared with the reported values for p-GaN HEMTs on silicon substrates with substrate grounded. The vertical breakdown voltage for the p-GaN-on-SiC material exceeded 3 kV with substrate grounded. In addition, the maximum drain current at 500 K was 48% of that at 300 K with a negligible threshold voltage shift. These results indicate the substantial potential of p-GaN gate HEMTs on SiC substrates for high-voltage power applications. [ABSTRACT FROM AUTHOR]

In this study, the negative shift of the threshold voltage (VTH) and degradation of the leakage current triggered by the ultraviolet (UV) light (375 nm) have been investigated when a large reverse gate-to-drain voltage was applied to a Si3N4/AlGaN/GaN metal-insulator-semiconductor high electron mobility transistor. However, an increase in leakage was not observed under the blue light or in the dark. The holes generated in the channel by UV illumination were attracted by the gate electrode owing to the reverse voltage. During the movement, holes were captured by border traps at very deep levels in the Si3N4 near AlGaN, leading to a negative shift of VTH that was difficult to recover. According to the simulation based on Silvaco Atlas TCAD, the trapped holes significantly increased the electric field strength in Si3N4. Therefore, as the injection barrier for electrons from the gate became thinner, it was easier for electrons to tunnel through the Si3N4. Finally, for the degraded devices under the UV light stress, Fowler-Nordheim tunneling was the dominant leakage conduction mechanism, as exhibited by the current density versus electric field strength curve fitting. In addition, the holes with high energies collided with Si3N4 and generated new defects at the edge of the gate near the drain side. [ABSTRACT FROM AUTHOR]

EGFR-tyrosine kinase inhibitors (TKIs) show efficacy against lung cancer, and afatinib has been used as a standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR rare mutations such as S768I, G719X, and L861Q. However, the efficacy of EGFR-TKIs against NSCLC with EGFR rare mutations of exon 18 E709X has been less studied. The present study aimed to analyze the efficacy and safety of EGFR-TKIs in NSCLC patients with rare mutations. Our study enrolled 15 NSCLC patients with exon 18 E709X mutation who were admitted to Zhejiang Cancer Hospital. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were analyzed. The ORR of the entire cohort of patients was 33.3%. The PFS of all patients with exon 18 E709X mutations was 10.9 months. The OS was not reached. The PFS of patients with exon 18 E709-T710delinsD and E709A/G/K mutations showed no significant difference (5.3 vs. 13.5 months, P = 0.238). A significant difference in OS was observed between patients with exon 18 E709-T710delinsD mutation and those with E709A/G/K mutation (12.2 months vs. not reached, P = 0.029). No significant difference in efficacy was observed between second- and third-generation TKIs for NSCLC patients with exon 18 E709X mutations (PFS: 13.5 vs. 10.9 months, P = 0.774; OS: 17.1 months vs. not reached, P = 0.072). New treatment-related adverse events were not observed. NSCLC patients with exon 18 E709X mutations may benefit from treatment with second- or third-generation EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Basic leucine zipper (bZIP) is a diverse transcription factor in plants that is involved in many stress responses, especially salt stress. However, the roles of bZIP genes in the common bean have not been elucidated. 84 proteins in common bean were identified here. Through phylogenetic analysis, the PvbZIPs were classified into five subfamilies, and these clusters were supported by several group-specific features, including gene structure, motifs, and cis-regulatory elements. Collinearity analysis revealed the connection between PvbZIPs and bZIPs from two other dicotyledonous species, namely Arabidopsis and Soybean (Glycine max). Expression patterns of the PvbZIPs genes indicated that they exhibit a tissue-specific manner at the sprouting stage. RNA-seq and qRT-PCR analyses indicated that PvbZIPs exhibit different expression patterns under salt stress in salt tolerance and salt-sensitive varieties. According to KEGG analysis of PvbZIPs-enriched pathways, PvbZIPs appear to target the abscisic acid (ABA) signaling pathway which might result in enhanced salt tolerance. Our findings elucidate on functional characterization of PvbZIP in Phaseolus vulgaris and its role in salt stress regulation through ABA. [ABSTRACT FROM AUTHOR]

High-entropy metal spinel oxide (HEO) is proved to be a promising oxygen evolution reaction (OER) catalyst with high catalytic performance and stability. A short routine synthesis process based on solution combustion synthesis was proposed to prepare (Co0.25Ni0.25Mn0.25Zn0.25)Fe2O4 spinel HEO in this work. During the process, the products were rapidly synthesized and melted due to the high-temperature reaction, and then quickly crystallized on the surface of nickel foam to form a nano-structure coating. With the aid of nano-scale spinel structure, the overpotential of non-activation HEO electrode reaches 276 mV at the current density of 10 mA·cm−2, and after 100 h i-t test, it can be further reduced to 230 mV, which proves the high activity of OER catalysis. The promotion of OER catalytic performance can be attributed to the surface reconstruction caused by the selective element leaching and the boost of oxygen vacancy, leading to the formation of nano-scale flocculation around spinel core after the long-term OER process. This work indicates a special casting process for functional materials and explores the application of rapid crystallization. [ABSTRACT FROM AUTHOR]

The etching process of high-performance recessed-gate InAlN/GaN high-electron mobility transistors (HEMTs) has been actively researched. This paper proposes a post-etching self-limited surface restoration method that effectively suppresses the etching damage, enhancing the transport properties of recessed-gate InAlN/GaN HEMTs. We fabricated planar-gate devices, inductively coupled plasma (ICP)-etched devices, and post-etching-treated (PET) devices. The damage caused by the ICP etching process severely deteriorated the transport properties of the devices. However, the post-etching process effectively inhibited the etching damage and improved the device transport properties. Through temperature-dependent tests and a simulation, the change in the peak transconductance was compared among different devices. The temperature-dependent optical phonon scattering and impurity-dependent remote charge scattering mechanisms were analyzed. The results confirmed that the etching damage significantly affected the channel electron scattering mechanism. The field-effect mobility showed a linear relationship with temperature, and the optical phonon scattering model illustrated that the field-effect mobility decreased with increasing temperature. The etching damage caused a decrease in the field-effect mobility from 1075.5 to 699.1 cm2/V·s, which increased the fitting error between this empirical line and the optical phonon scattering fitting curve from 0.086 to 0.948, similar to the remote charge scattering fitting curve. The combined error range is from 0.896 to 0.054. [ABSTRACT FROM AUTHOR]

Conclusion: This study proposed and fabricated a β-Ga2O3 SBD-based rectifier with embedded microchannels in a ceramic substrate for active cooling for the first time. Experimental results demonstrate that this technique can increase the output power from 3.2 to 21.3 W, consuming only 0.9 mW of pump power. The achievements in this work indicate that embedded cooling offers a powerful technique to suppress the thermal effects on Ga2O3 devices and circuits, thereby improving their electrical performance. [ABSTRACT FROM AUTHOR]

Conclusion: The direct current and radio frequency of DCGC-HEMT and DCTB-HEMT were systematically investigated. Owing to the utilization of a graded-AlGaN bottom barrier to provide more carriers and shield traps in the buffer, DCGC-HEMT exhibited greater saturated drain current and suppression in drain lag, enabling it to show greater output performance than DCTB-HEMT. The improvement in the former’s superior large-signal characteristic indicates its potential for high-performance RF PA applications. [ABSTRACT FROM AUTHOR]

In this study, we investigate heavy ion irradiation effects on commercial 650 V p-GaN normally-off HEMTs. Ge and Cl ions are used to irradiate the GaN devices in the experiments. Ge and Cl ion beam irradiation have little impact on the output characteristics of GaN devices. After heavy ion irradiation, the leakage currents between source and drain electrodes increase significantly under off-state, decreasing the breakdown voltage (BVDS) sharply. Additionally, Ge and Cl ion irradiation have little effect on the trap states under the gate electrode; thus, the gate leakage currents increase slightly. Many line-shaped crystal defects extending from the surface to the GaN buffer layer can be captured using a transmission electron microscope after Ge/Cl ion irradiation. The buffer layers of the irradiated devices were damaged, and the leakage path was generated in the buffer layer. Defect percolation process in buffer layer is the dominant factor of irradiated high-voltage GaN device failure. [ABSTRACT FROM AUTHOR]