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Fear generalization is a crucial mechanism underlying maladaptive behavior, but factors influencing this process are not fully understood. We investigated the effects of cue training and context on fear generalization and how cognitive rules influence responses to different conditions. We also examined the role of stimulus intensity in fear generalization to provide insight into fear generalization mechanisms. Participants (n = 104) completed a fear emotion task with two stages: acquisition and generalization testing. Subjective fear expectancy ratings were used as outcome measures. Participants who received single threat cue training exhibited stronger fear generalization responses than those who received discrimination training with threat and safe cues. Participants who received discrimination training and used linear rules had the strongest fear response to the largest stimulus. Therefore, a safe cue may mitigate fear generalization but could increase fear responses to more intense stimuli. Altering context did not change the fear generalization response because fear generalization is mainly governed by the association between the conditioned stimulus and the unconditioned fear stimulus. The present study emphasizes the multifaceted nature of fear generalization and the importance of examining multiple factors to understand this phenomenon. These findings elucidate fear learning and provide insights needed for effective interventions for maladaptive behavior.

Graphene oxide (GO) exhibits great application in rubber industry due to its unique two-dimensional nanosheet structure, significant specific surface area, good barrier property, and high reactivity. However, different rubbers, such as carboxylated nitrile butadiene rubber (XNBR), natural rubber (NR), and styrene butadiene rubber (SBR), have different interactions with GO, which has great influence on the reinforcement effect of GO to the rubber matrix. In this work, the enhancement mechanism of GO on NR, SBR, and XNBR was studied by combining experiments with molecular dynamics (MD) simulation. The results show that GO/XNBR nanocomposites had the smallest potential energy difference (ΔWa), mean square displacement (MSD), and free volume fraction (FFV), resulting in excellent solvent resistance, and dynamic and mechanical properties. This study provides a new way to explore the macroscopic properties of rubber nanocomposites through molecular-level simulation.

A new ocean-atmosphere-wave regional coupled model named Windwave version 1.0 for simulating and predicting winds and waves has been developed for the Northwest Pacific Ocean. In particular, the global-to-regional nesting technique is adopted for the ocean component to alleviate the bias due to the inconsistency in the lateral boundary. This paper is devoted to describing the coupling details of Windwave and the initialization scheme and assessing its basic performance, especially in predicting surface winds and significant wave heights (SWH) on the weather timescale. The control experiment set contains 31 experiments for August 2020, with seven typhoons passing through the Northwest Pacific. Each experiment starts at 0:00 am UTC of each day and runs for three days. Experiment results show that the new coupled model performs well in predicting surface winds, SWH, surface air temperature, and sea surface temperature on the weather timescale. In particular, the Root Mean Square Errors (RMSEs) of surface winds at 10 m height over the Northwest Pacific of the control experiment are 1.82 m s-1, 2.22 m s-1, and 2.59 m s-1, respectively, at lead times of 24 h, 48 h, and 72 h. Meanwhile, the RMSEs of SWH at lead times of 24 h, 48 h, and 72 h are 0.39 m, 0.43 m, and 0.51 m. In addition, we have explored the impacts of the different sea surface aerodynamic roughness parameterization schemes on predicting surface winds and SWH. In total, five different sea surface aerodynamic roughness parameterization schemes are adopted, corresponding to one control set and four sensitivity sets of experiments. Under normal conditions, the sea surface aerodynamic roughness parameterization scheme considering the effects of wind-wave direction tends to perform better for winds and waves, while that depending on wave age and SWH tends to perform worse. Under extreme wind and wave conditions, the schemes considering the effects of wind-wave direction and that considering wave age and peak wave length have better performance. These findings can provide new insights for developing a more advanced sea surface aerodynamic roughness parameterization scheme.

Dual-atom catalysts possess a significant potential for promoting CO2 photoreduction to lucrative solar fuels. However, the precise construction of the diatomic sites that simultaneously foster light absorption and catalytic activity is a formidable challenge, as both processes follow distinct pathways in the photocatalyst. Herein, a facile electrostatic-driven self-assembling approach is employed to realize a bifunctional architecture of a diatomic LaNi-Phen (Phenanthroline)/covalent organic framework (COF-5) photocatalyst. The La site acts as an optically active center for the photoinduced generation of carriers, while the Ni site serves as the catalytically active center for highly selective CO2-to-CO reduction enabled by directional charge transfer via COF-5. Density functional theory (DFT) calculations and in-situ characterization reveal the efficient synergistic effect of the La-Ni double-atomic sites, leading to decreased reaction energy barriers of *COOH intermediate and enhanced CO2-to-CO conversion. As a result, in the absence of any additional photosensitizers, a 15.2 times enhancement of the CO2 reduction rate (605.8 µmol·g− 1·h− 1) over that of pristine COF-5 colloid (39.9 µmol·g− 1·h− 1) and an improvement in CO selectivity to 98.2% are achieved. This work presents a novel strategy for integrating optically and catalytically active centers, which results in a diatomic synergy effect enabling high-performance photocatalytic CO2 reduction.

The VG161 represents the first recombinant oncolytic herpes simplex virus type 1 carrying multiple synergistic antitumor immuno-modulating factors. Here, we report its antitumor mechanisms and thus provide firm theoretical foundation for the upcoming clinical application in pancreatic cancer. Generally, the VG161-mediated antitumor outcomes were analyzed by a collaboration of techniques, namely the single-cell sequencing, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADSI-MSI) and nanostring techniques. In vitro, the efficacy of VG161 together with immune checkpoint inhibitors (ICIs) has been successfully shown to grant a long-term antitumor effect by altering tumor immunity and remodeling tumor microenvironment (TME) metabolisms. Cellular functional pathways and cell subtypes detected from patient samples before and after the treatment had undergone distinctive changes including upregulated CD8+ T and natural killer cells. More importantly, significant antitumor signals have emerged since the administration of VG161 injection. In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong antitumor potential. The more robusting antitumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials.

Oncolytic virus therapy has shown benefits for multiple cancers, while limitations remain for traditional treatment. However, few studies have concentrated on comparing whether oncolytic virus combined with traditional treatment is better than traditional treatment alone in patients with cancer. We conducted a meta-analysis of the curative effect and safety of oncolytic virus combination therapy. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases comprehensively for articles comparing oncolytic virus combined with traditional treatment to traditional treatment alone in patients with cancer. A meta-analysis and trial sequential analysis were performed. A total of 12 studies involving 1494 patients (combination therapy group, 820 patients; traditional treatment group, 674 patients) were included in the study. Compared with traditional treatment alone, combination therapy was significantly associated with high objective response rate [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01–1.82, p = 0.04]. There were no significant differences for other outcomes such as 1- and 2-year survival rate, and 4- and 12-month progression-free survival rate. Combination therapy was significantly associated with high incidence of grade ≥ 3 adverse effects (OR 1.47, 95% CI 1.06–2.05, p = 0.02) and high incidence of grade ≥ 3 neutropenia (OR 1.65, 95% CI 1.13–2.43, p = 0.01). There were no significant differences for other grade ≥ 3 adverse effects, e.g., gastrointestinal adverse effects, influenza-like illness, fatigue, anemia, and thrombocytopenia. Despite partially increased toxicity, the combination therapy improves the effectiveness of cancer treatment. However, high-quality, large-scale studies are needed to evaluate its effectiveness and safety.

Perovskite solar cells (PSCs) have developed rapidly in the past 10 years. However, they are faced with a huge challenge for stability improvement because of the volatile organic components in the ...

With the rapid development of perovskite solar cells (PSCs), it is critical to explore efficient and low-cost inorganic hole transport materials (HTMs) to solve the instability issue of the traditional organic HTM spiro-OMeTAD. Herein, Cu12Sb4S13 quantum dots (QDs) are applied as inorganic HTMs in n–i–p planar PSCs, the bandgap aligned the QDs is achieved by the modulation of the QD size to accelerate hole transport from the perovskite layer to QDs, and a power conversion efficiency (PCE) of 14.13% is achieved for 5.7 nm sized QDs. IPCE and UV-vis spectra indicate that the light absorption intensity of Cu12Sb4S13 QD based PSCs is slightly higher than that of the spiro-OMeTAD based one, which enables the enhancement of JSC (21.85 mA cm−2) for PSCs. The excellent hole transport behavior of Cu12Sb4S13 QDs proves that Cu12Sb4S13 QDs may be considered as an efficient and potential candidate of HTMs in PSCs. Moreover, the stability of the Cu12Sb4S13 QD based PSCs is significantly improved compared with that of the spiro-OMeTAD based one due to the high stability of Cu12Sb4S13 QDs and 91% of the initial PCE is retained after 30 days in ambient air.

Human tongue squamous carcinoma cell lines transfected with HPV16E6E7 gene were established to provide a model for further study of HPV16 E6E7-related human tongue squamous carcinoma cell lines .Plasmid pEGFR/HPV16 of E6E7 and plasmid pEGFR/HPV16 of No E6E7 were constructed.Human tongue squamous carcinoma cell lines including SCC9 and SCC15 were infected by liposome transfection and would be highly selected by antibiotic .Fluorescence imaging, RT-PCR and Westernblot were used to detect the expression of HPV16 E6E7 in cells.The biological characteristics of human tongue squamous carcinoma cell lines infected with HPV16 E6E7 were detected by CCK-8 and wound healing assay. The human tongue squamous carcinoma cell lines transfected with HPV16 E6E7 gene were successfully established and identified, and the proliferation and migration ability of the human tongue squamous carcinoma cell lines infected with HPV16 E6E7 gene was significantly stronger than that of the blank group.Human tongue squamous carcinoma cell lines infected with HPV16 E6E7 were more malignant, and their proliferation and migration ability were higher than those not infected with HPV16 E6E7.

Social anxiety disorder (SAD) is one of the most common lifelong anxiety disorders. Although cognitive behavioural therapy (CBT) has proven to be effective in treating people with SAD, it may not be available for a considerable proportion of patients. Internet-based CBT (ICBT) is more accessible than face-to-face treatment. This meta-analysis evaluated the efficacy of ICBT in patients with SAD. We searched five databases, PubMed, Cochrane Central Register of Controlled Trials, Health Management Information Consortium, Ovid MEDLINE and EMBASE, and identified 20 eligible randomized controlled trials published from inception to 25 July 2020, with the outcome data from 1,743 participants. The results indicated that ICBT had a significant positive effect on patients with SAD compared with the control groups (g = -0.55). A subgroup analysis revealed that ICBT and CBT had an equal effect on treating patients with SAD (g = -0.18). There was also no difference between ICBT and ICBT plus other therapies in the treatment of patients with SAD (g = -0.07). The effect size of ICBT on patients with SAD was maintained at the 6-month follow-up (g = -0.08) and at the 12-month follow-up (g = -0.17). The findings of this review demonstrated that ICBT can significantly reduce SAD symptoms and that ICBT and face-to-face CBT produce equivalent effects. The results of this meta-analysis contributed to the literature on ICBT for the treatment of patients with SAD, although numerous aspects of ICBT were identified for future investigations.

Renal dysplasia, the major cause of childhood renal failure, is characterized by defective branching morphogenesis and nephrogenesis. Beta-catenin, a transcription factor and cell adhesion molecule, is markedly increased in the nucleus of kidney cells in human renal dysplasia and contributes to its pathogenesis by altering target genes that are essential for kidney development. Quercetin, a naturally occurring flavonoid, reduces nuclear beta-catenin levels and reduces beta-catenin transcriptional activity. In this study, we utilized wild type and dysplastic mouse kidney organ explants to determine if quercetin reduces beta-catenin activity during kidney development and whether it improves the severity of renal dysplasia. In wild type kidney explants, quercetin treatment resulted in abnormal branching morphogenesis and nephrogenesis in a dose dependent manner. In wild type embryonic kidneys, quercetin reduced nuclear beta-catenin expression and decreased expression of beta-catenin target genes Pax2, Six2, and Gdnf, which are essential for kidney development. Our RDB mouse model of renal dysplasia recapitulates the overexpression of beta-catenin and histopathological changes observed in human renal dysplasia. RDB kidneys treated with quercetin resulted in improvements in the overall histopathology, tissue organization, ureteric branching morphogenesis, and nephrogenesis. Quercetin treatment also resulted in reduced nuclear beta-catenin and reduced Pax2 expression. These improvements were associated with the proper organization of vimentin, NCAM, and E-cadherin, and a 45% increase in the number of developing and maturing nephrons. Further, our results show that in human renal dysplasia, beta-catenin, vimentin, and e-cadherin also have abnormal expression patterns. Taken together, these data demonstrate that quercetin treatment reduces nuclear beta-catenin and this is associated with improved epithelial organization of developing nephrons, resulting in increased developing nephrons and a partial rescue of renal dysplasia.

All-inorganic CsPbI3 quantum dots perovskite solar cells (QDPSCs) have wide potential application due to their excellent photoelectric properties with high environmental stability. However, the poor interface contact between the light absorption layer and hole transport layer (HTL) results in the serious carrier recombination and the large open-circuit voltage (VOC) loss. Herein, we introduce the insulating PMMA (poly(methyl methacrylate)) buffer layer into CsPbI3 quantum dots (QDs)/Cu12Sb4S13 QDs HTL interface in all-inorganic QDPSCs with the structure of FTO/c-TiO2/m-TiO2/CsPbI3 QDs/Cu12Sb4S13 QDs/Au. The interface carrier recombination is obviously suppressed and the significant VOC improvement from 1.04 V to 1.14 V is obtained with the incorporated PMMA buffer layer. The devices with PMMA buffer layer show the enhanced power conversion efficiency (PCE) of 10.99%, and the improvement of 9.71% is achieved compared to that of the control devices (10.02%). The stability is significantly enhanced due to the intrinsic hydrophobic characteristic of PMMA, and the devices retain 62.69% of their initial PCE after stored in air condition for 15 days, which is greatly improved compared with the control device without PMMA.

This study examines the formation of circulation patterns favorable to wintertime extreme precipitation events over South China between 1979 and 2013. During these extreme precipitation events, a barotropic wave train having seven centers of action was observed to extend from the Arabian Sea to the west coast of the North American continent with a maximum amplitude at 300 hPa. A center of action located over South China, comprised of cyclonic anomalies, favored powerful updrafts and large-scale moisture convergence over South China. About 77% of wintertime extreme precipitation events in South China were preceded by European blocking events. The formation mechanism for the 141 precipitation events with pre-existing European blocking highs is presented. Rossby wave energy propagation associated with the positive phase of circumglobal teleconnection enabled the European blocking event with a lead time of $$\sim$$ 10 days to generate cyclonic anomalies over South China. Moreover, significant warm anomalies were present over South China before the onset of these blocking-related extreme precipitation events. Increases in atmospheric moisture holding capacity associated with these warm anomalies enabled a buildup of precipitable water via moisture fluxes into South China through the western and southern boundaries. Onset of the extreme precipitation events was then triggered by the intrusion of cold temperature anomalies from the north, which lifted warm moist air upward from the surface and lowered the moisture holding capacity, producing large amounts of precipitation.

Laser soldering has been widely used in the connection of the electronic components and printed circuit boards. Normally, the temperature and thermal stress of solder joints significantly influence the soldering performance and the reliability of solder joints. However, it is difficult to be accurately measured by the experiment during laser soldering process. In order to reveal the effect of laser process parameters on the temperature and thermal stress of SnAgCu solder joints, a novel 3D transient thermo-mechanical coupling numerical model is proposed using finite element method. The numerical simulation results reveal that the temperature and the thermal stress as well as the deformation of the as-soldered samples are proportional to laser output power and output time. These results demonstrate that the fine and uniform microstructure is obtained for SnAgCu solder and the micro Vickers hardness reaches to the maximum value of 38.3 N at the condition of laser output power of 16 W and laser output time of 0.8 s. The good consistency between the experimental and simulation results proves that the finite element model may effectively predict the temperature distribution and stress distribution, which provides a new pathway for the optimization of the laser soldering parameters in the application of electronic components and PCB.

Circulation patterns associated with cold events over East Asia during the winter months of 1948–2014 are classified into four regimes by applying a k-means clustering method based on the area-weighted pattern correlation. The earliest precursor signals for two regimes are anticyclonic anomalies, which evolve into Ural and central Siberian blocking-like circulation patterns. The earliest precursor signals for the other two regimes are cyclonic anomalies, both of which evolve to amplify the East Asian trough (EAT). Both the blocking-like circulation patterns and amplified EAT favor the initialization of cold events. On average, the blocking-related regimes tend to last longer. The lead time of the earliest precursor signal for the central Siberian blocking-related regime is only 4 days, while those for the other regimes range from 16 to 18 days. The North Atlantic Oscillation plays essential roles both in triggering the precursor for the Ural blocking-related regime and in amplifying the precursors for all regimes. All regimes preferentially occur during the positive phase of the Eurasian teleconnection pattern and the negative phase of the El Nino–Southern Oscillation. For three regimes, surface cooling is primarily due to reduced downward infrared radiation and enhanced cold advection. For the remaining regime, which is associated with the southernmost cooling center, sensible and latent heat release and horizontal cold advection dominate the East Asian cooling.

To examine the combined effects of the different spatial patterns of the Arctic Oscillation (AO) related sea level pressure (SLP) anomalies and the El Nino/Southern Oscillation (ENSO) related sea surface temperature (SST) anomalies on the wintertime surface temperature anomalies over East Asia, a nonlinear method based on self-organizing maps is employed. Investigation of identified regimes reveals that the AO can affect East Asian temperature anomalies when there are significant SLP anomalies over the Arctic Ocean and northern parts of Eurasian continent. Analogously, ENSO is found to affect East Asian temperature anomalies when significant SST anomalies are present over the tropical central Pacific. The regimes with the warmest and coldest temperature anomalies over East Asia are both associated with the negative phase of the AO. The ENSO-activated, Pacific-East Asian teleconnection pattern could affect the higher latitude continental regions when the impact of the AO is âĂŸswitched offâĂŹ. When the spatial patterns of the AO and ENSO have significant, but opposite, impacts on the coastal winds, no obvious temperature anomalies can be observed over South China. Further, the circulation state with nearly the same AO and Nino3 indices may drive rather different responses in surface temperature over East Asia. The well-known continuous weakening (recovery) of the East Asian winter monsoon that occurred around 1988 (2009) can be attributed to the transitions of the spatial patterns of the SLP anomalies over the Arctic Ocean and Eurasian continent, through their modulation on the occurrences of the Ural and central Siberian blocking events.

The co-occurrence of wintertime temperature anomalies over eastern Asia and eastern North America is examined. The winter days during 1948–2014 are assigned to nine regimes by applying the Self-Organizing Map clustering method to the area-averaged land surface temperature anomalies over these two regions. About half of the winter days are associated with concurrent temperature anomalies. The occurrence of the concurrent/non-concurrent regimes is closely related to the large-scale circulation conditions. The Eurasian teleconnection pattern and the Pacific-North American teleconnection pattern are two dominant large-scale circulation modes associated with the co-occurrence of the temperature anomalies, through their impacts on the intensities of the corresponding troughs. The precursor analysis reveals that the lead time of the early signals for the concurrent cold anomalies is about four days longer than that for the concurrent warm anomalies. In addition, the average lead time of the precursor signals for the wintertime temperature anomalies over eastern Asia is longer than that is over eastern North America.

Nine potential vorticity (PV) regimes over East Asia are identified by applying a Self-Organizing Map and Hierarchical Ascendant Classification regime analysis to the daily PV reanalysis fields on the 300K isentropic surface for December-March 1948–2014. According to the surface temperature anomalies over East Asia, these nine regimes are further classified into three classes, i.e., cold class (three regimes), warm class (four regimes), and neutral class (two regimes). The PV-based East Asian winter monsoon index (EAWMI) is used to study the relationship between PV distributions and the temperature anomalies. The magnitude of cold (warm) anomalies over the land areas of East Asia increases (decreases) quasi-linearly with the EAWMI. Regression analysis reveals that cold temperature anomalies preferentially occur when the EAWMI exceeds a threshold at ∼0.2PVU (where 1PVU≡10−6 m2 Kkg−1 s−1). PV inversion uncovers the mechanisms behind the relationships between the PV regimes and surface temperature anomalies, and reveals that cold (warm) PV regimes are associated with significant warming (cooling) in the upper troposphere and lower stratosphere. On average, cold regimes have longer durations than warm regimes. Interclass transition probabilities are much higher for paths from warm/neutral regimes to cold regimes than for paths from cold regimes to warm/neutral regimes. Besides, intraclass transitions are rare within the warm or neutral regimes. The PV regime analysis provides insight into the causes of severe cold spells over East Asia, with blocking circulation patterns identified as the primary factor in initiating and maintaining these cold spells.

Car following models usually assume that individual drivers tend to keep a minimum safe distance from the vehicle in front of themselves, or tend to drive at a desired velocity. Through the analysis of NGSIM data, it is found that the distance between leader car and follower car is often not the minimum safe distance when the driver maintains similar velocity with the leading vehicle. Moreover, due to miss perception of leading vehicle's velocity, the following vehicle's desired velocity is not equal to the leading vehicle's, especially when the leading vehicle's velocity changes greatly. In this paper, the comfortable driving distance is proposed to replace the minimum safe distance in the traditional car-following model, and the calculation method of the desired velocity is given. Logistic function was used to improve the linear function in the spring-damper car-following model, which fit the changing of driving velocity of follower vehicles better. Simulation results are provided to validity the model developed in this paper.