Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Publisher Correction: The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.

In the version of this article initially published, the institution name for affiliation 3 (Maryland Anderson Cancer Center) was incorrect. The correct institution is MD Anderson Cancer Center. The error has been corrected in the HTML and PDF versions of the article.

Corrigendum: The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.

This corrects the article DOI: 10.1038/ni.3748.

The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.

An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under Treg cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced Treg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of Treg cells and TH17 cells.

NPSV-deep: a deep learning method for genotyping structural variants in short read genome sequencing data.

MOTIVATION: Structural variants (SVs) play a causal role in numerous diseases but can be difficult to detect and accurately genotype (determine zygosity) with short-read genome sequencing data (SRS). Improving SV genotyping accuracy in SRS data, particularly for the many SVs first detected with long-read sequencing, will improve our understanding of genetic variation. RESULTS: NPSV-deep is a deep learning-based approach for genotyping previously reported insertion and deletion SVs that recasts this task as an image similarity problem. NPSV-deep predicts the SV genotype based on the similarity between pileup images generated from the actual SRS data and matching SRS simulations. We show that NPSV-deep consistently matches or improves upon the state-of-the-art for SV genotyping accuracy across different SV call sets, samples and variant types, including a 25% reduction in genotyping errors for the Genome-in-a-Bottle (GIAB) high-confidence SVs. NPSV-deep is not limited to the SVs as described; it improves deletion genotyping concordance a further 1.5 percentage points for GIAB SVs (92%) by automatically correcting imprecise/incorrectly described SVs. AVAILABILITY AND IMPLEMENTATION: Python/C++ source code and pre-trained models freely available at https://github.com/mlinderm/npsv2.

Palladium-Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO-1233zd (E).

3-Indole-3-one is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for synthesizing trifluoromethylated 3-indoleketones by Pd(0)-catalyzed carbonylation was introduced. In the absence of additives, 1-chloro-3,3,3-trifluoropropyl (an inexpensive and environmentally friendly synthetic block of trifluoromethyl) reacts with indole and carbon monoxide to generate trifluoromethylindole ketones with good yields, regioselectivity, and chemical selectivity; furthermore, the products exhibit strong resistance to basic functional groups, such as alkynes, aldehydes, and esters. In addition to the conversion of indole compounds into corresponding products, pyrrole and heteroindole may be suitable for corresponding chemical transformations. This study provides a synthetic method for the further construction of trifluoromethylated 3-indole ketones.

The effects of emotion on retrospective duration memory using virtual reality.

Our memories for temporal duration may be colored by the emotions we experience during an event. While emotion generally enhances some aspects of memory, temporal duration has been shown to be particularly susceptible to emotion-induced distortions. However, prior work has faced difficulty when studying this phenomenon, having to make some trade-offs on ecological validity or experimental control. Here, we sought to bridge this gap by studying the effects of emotion on temporal duration memory using virtual reality. In the present study, a final sample of 69 participants experienced a series of negative-emotional and neutral worlds within virtual reality. Following this, participants provided ratings of emotionality (arousal, valence, pleasantness) and retrospective duration estimates (i.e., remembered time). We hypothesized that negative events would be recalled as having a greater duration than neutral events (H1). We additionally hypothesized that negative, but not neutral, events would be recalled as being longer than the true duration (H2). The results supported H1 while failing to provide evidence in support of H2. Together, the results bolster the importance of emotion, especially negative emotion, in shaping how we remember the temporal unfolding of the past.

Low-Dimensional Phase Regulation to Restrain Non-Radiative Recombination for Sky-Blue Perovskite LEDs with EQE Exceeding 15 .

Achieving efficient blue electroluminescence (EL) remains the fundamental challenge that impedes perovskite light-emitting diodes (PeLEDs) towards commercial applications. The bottleneck accounting for the inefficient blue PeLEDs is broadly attributed to the poor-emissive blue perovskite emitters based on either mixed halide engineering or reduced-dimensional strategy. Herein, we report the high-performing sky-blue PeLEDs (490 nm) with the maximum EQE exceeding 15 % by incorporating a molecular modifier, namely 4,4'-Difluorophenone, for significantly suppressing the non-radiative recombination and tuning of the low-dimensional phase distribution of quasi-2D blue perovskites, which represents a remarkable paradigm for developing the new generation of blue lighting sources.

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.

Visualizing the Surface Photocurrent Distribution in Perovskite Photovoltaics.

Defect states play an important role in the photovoltaic performance of metal halide perovskites. Particularly, the passivation of surface defects has made great contributions to high-performance perovskite photovoltaics. This highlights the importance of understanding the surface defects from a fundamental level by developing more accurate and operando characterization techniques. Herein, a strategy to enable the surface carriers and photocurrent distributions on perovskite films to be visualized in the horizontal direction is put forward. The visual image of photocurrent distribution is realized by combining the static local distribution of carriers provided by scanning near-field optical microscopy with the dynamic transporting of carriers achieved via a scanning photocurrent measurement system. Taking a surface passivated molecule as an example, a comprehensive defect scene including static and dynamic as well as local and entire conditions is obtained using this strategy. The comprehensive analysis of the trap states in perovskite films is pioneered vertically and horizontally, which will powerfully promote the deep understanding of defect mechanisms and carrier behavior for the goal of fabricating high-performance perovskite optoelectronic devices.

The DmeRF System Is Involved in Maintaining Cobalt Homeostasis in Vibrio parahaemolyticus.

Although cobalt (Co) is indispensable for life, it is toxic to cells when accumulated in excess. The DmeRF system is a well-characterized metal-response system that contributes to Co and nickel resistance in certain bacterial species. The Vibrio parahaemolyticus RIMD 2210633 genome also harbors a dmeRF operon that encodes a multiple antibiotic resistance regulator family transcriptional regulator and a cation diffusion facilitator family protein. Quantitative real-time PCR, growth curves analysis, inductively coupled plasma-mass spectrometry, ß-galactosidase activity assays, electrophoretic mobility shift assays, and a mouse infection experiment were performed to characterize the function of the DmeRF system in V. parahaemolyticus. Zinc, copper, and Co significantly increase dmeF expression, with Co inducing the greatest increase. DmeF promotes V. parahaemolyticus growth under high-Co conditions. Additionally, increased accumulation of cellular Co in the ΔdmeF mutant indicates that DmeF is potentially involved in Co efflux. Moreover, DmeR represses the dmeRF operon by binding directly to its promoter in the absence of Co. Finally, the DmeRF system was not required for V. parahaemolyticus virulence in mice. Collectively, our data indicate that the DmeRF system is involved in maintaining Co homeostasis in V. parahaemolyticus and DmeR functioning as a repressor of the operon.

Mn2NiO4 spinel catalyst for high-efficiency selective catalytic reduction of nitrogen oxides with good resistance to H2O and SO2 at low temperature.

Mn-Ni oxides with different compositions were prepared using standard co-precipitation (CP) and urea hydrolysis-precipitation (UH) methods and optimized for the selective catalytic reduction of nitrogen oxides (NOx) by NH3 at low temperature. Mn(2)Ni(1)Ox-CP and Mn(2)Ni(1)Ox-UH (with Mn:Ni molar ratio of 2:1) catalysts showed almost identical selective catalytic reduction (SCR) catalytic activity, with about 96% NOx conversion at 75°C and ~99% in the temperature range from 100 to 250°C. X-ray diffraction (XRD) results showed that Mn(2)Ni(1)Ox-CP and Mn(2)Ni(1)Ox-UH catalysts crystallized in the form of Mn2NiO4 and MnO2-Mn2NiO4 spinel, respectively. The latter gave relatively good selectivity to N2, which might be due to the presence of the MnO2 phase and high metal-O binding energy, resulting in low dehydrogenation ability. According to the results of various characterization methods, it was found that a high density of surface chemisorbed oxygen species and efficient electron transfer between Mn and Ni in the crystal structure of Mn2NiO4 spinel played important roles in the high-efficiency SCR activity of these catalysts. Mn(2)Ni(1)Ox catalysts presented good resistance to H2O or/and SO2 with stable activity, which benefited from the Mn2NiO4 spinel structure and Eley-Rideal mechanism, with only slight effects from SO2.

Response of Pseudomonas fluorescens to dimethyl phthalate.

Dimethyl phthalate (DMP) is a ubiquitous pollutant that is very harmful to organisms due to its mutagenicity, teratogenicity and carcinogenicity. Pseudomonas fluorescens (P. fluorescens) is one of the most important bacteria in the environment. In this study, the response of P. fluorescens to DMP was investigated. It was found that DMP greatly inhibited the growth and glucose utilization of P. fluorescens when the concentration of DMP was ranged from 20 to 40 mg/l. The surface hydrophobicity and membrane permeability of P. fluorescens were also increased by DMP. DMP could lead to the deformations of cell membrane and the mis-opening of membrane channels. RNA-Seq and RT-qPCR results showed that the expression of some genes in P. fluorescens were altered, including the genes involved in energy metabolism, ATP-binding cassette (ABC) transporting and two-component systems. Additionally, the productions of lactic acid and pyruvic acid were reduced and the activity of hexokinase was inhibited in P. fluorescens by DMP. Clearly, the results suggested that DMP contamination could alter the biological function of P. fluorescens in the environment.

Response of Arthrobacter QD 15-4 to dimethyl phthalate by regulating energy metabolism and ABC transporters.

Ubiquitous dimethyl phthalate (DMP) has severely threatened environmental safety and the health of organisms. Therefore, it is necessary to degrade DMP, removing it from the environment. Microbiological degradation is an efficient and safe method for degrading DMP. In this study, the response of Arthrobacter QD 15-4 to DMP was investigated. The results showed that the growth of Arthrobacter QD 15-4 was not impacted by DMP and Arthrobacter QD 15-4 could degrade DMP. RNA-Seq and RT-qPCR results showed that DMP treatment caused some changes in the expression of key genes in Arthrobacter QD 15-4. The transcriptional expressions of pstSCAB and phoU were downregulated by DMP. The transcriptional expressions of potACD, gluBC, oppAB, pdhAB, aceAF, gltA were upregulated by DMP. The genes are mainly involved in regulating energy metabolism and ATP-binding cassette (ABC) transporters. The increasing of pyruvic acid and citrate in Arthrobacter QD 15-4 further supported the energy metabolism was improved by DMP. It was clearly shown that Arthrobacter QD 15-4 made response to dimethyl phthalate by regulating energy metabolism and ABC transporters.

Lead Isolation and Capture in Perovskite Photovoltaics toward Eco-Friendly Commercialization.

Perovskite solar cells (PSCs) are developed rapidly in efficiency and stability in recent years, which can compete with silicon solar cells. However, an important obstacle to the commercialization of PSCs is the toxicity of lead ions (Pb2+) from water-soluble perovskites. The entry of free Pb2+ into organisms can cause severe harm to humans, such as blood lead poisoning, organ failure, etc. Therefore, this work reports a "lead isolation-capture" dual detoxification strategy with calcium disodium edetate (EDTA Na-Ca), which can inhibit lead leakage from PSCs under extreme conditions. More importantly, leaked lead exists in a nontoxic aggregation state chelated by EDTA. For the first time, in vivo experiments are conducted in mice to systematically prove that this material has a significant inhibitory effect on the toxicity of perovskites. In addition, this strategy can further enhance device performance, enabling the optimized devices to achieve an impressive power conversion efficiency (PCE) of 25.19%. This innovative strategy is a major breakthrough in the research on the prevention of lead toxicity in PSCs.

Cooperative Effect of Ni-Decorated Monolayer WS2, NiO, and AC on Improving the Flame Retardancy and Mechanical Property of Polypropylene Blends.

Improving the residual char of polypropylene (PP) is difficult due to the preferential complete combustion. Here, we designed a combination catalyst that not only provides physical barrier effects, but also dramatically promotes catalytic charring activity. We successfully synthesized WS2 monolayer sheets decorated with isolated Ni atoms that bond covalently to sulfur vacancies on the basal planes via thiourea. Subsequently, PP blends composed of 8 wt.% Ni-decorated WS2, NiO, and activated carbon (AC) were obtained (ENi-SWS2-AC-PP). Combining the physical barrier effects of WS2 monolayer sheets with the excellent catalytic carbonization ability of the ENi-SWS2-AC combination catalyst, the PP blends showed a remarkable improvement in flame retardancy, with the yield of residual char reaching as high as 41.6 wt.%. According to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations, it was revealed that the microstructure of residual char contained a large number of carbon nanotubes. The production of a large amount of residual char not only reduced the release of pyrolytic products, but also formed a thermal shield preventing oxygen and heat transport. Compared to pure PP, the peak heat release rate (pHRR) and total heat release rate (THR) of ENi-SWS2-AC-PP were reduced by 46.32% and 26.03%, respectively. Furthermore, benefiting from the highly dispersed WS2, the tensile strength and Young's modulus of ENi-SWS2-AC-PP showed similar values to pure PP, without sacrificing the toughness.

Research on Wide-Temperature Rechargeable Sodium-Sulfur Batteries: Features, Challenges and Solutions.

Sodium-sulfur (Na-S) batteries hold great promise for cutting-edge fields due to their high specific capacity, high energy density and high efficiency of charge and discharge. However, Na-S batteries operating at different temperatures possess a particular reaction mechanism; scrutinizing the optimized working conditions toward enhanced intrinsic activity is highly desirable while facing daunting challenges. This review will conduct a dialectical comparative analysis of Na-S batteries. Due to its performance, there are challenges in the aspects of expenditure, potential safety hazards, environmental issues, service life and shuttle effect; thus, we seek solutions in the electrolyte system, catalysts, anode and cathode materials at intermediate and low temperatures (T < 300 °C) as well as high temperatures (300 °C < T < 350 °C). Nevertheless, we also analyze the latest research progress of these two situations in connection with the concept of sustainable development. Finally, the development prospects of this field are summarized and discussed to look forward to the future of Na-S batteries.

Synergistic Effect of Activated Carbon, NiO and Al2O3 on Improving the Thermal Stability and Flame Retardancy of Polypropylene Composites.

It is difficult to enhance the char yields of polypropylene (PP) due to the preferential complete combustion. Successful formation of abundant char layer structure of PP upon flammability was obtained due to the synergistic effect of NiO, Al2O3 and activated carbon (AC). From characterization of scanning electron microscopy (SEM) and transmission electron microscopy (TEM), it was revealed that the microstructure of residual char contained large amount of carbon nanotubes. Compared to the modification of AC, NiO and Al2O3 alone, the combination of AC, NiO and Al2O3 dramatically promotes the charring ability of PP. In the case of AC and NiO, NiO plays a role of dehydrogenation, resulting in the degradation product, while AC mainly acts as carbonization promoter. The addition of Al2O3 results in higher dispersion and smaller particle size of NiO, leading to greater exposure of active sites of NiO and higher dehydrogenation and carbonization activity. Compared to the neat PP, the decomposition temperature of the PP modified by combined AC, NiO and Al2O3 was increased by 90 ℃. The yield of residual char of AC-5Ni-Al-PP reached as high as 44.6%. From the cone calorimeter test, the heat release rate per unit area (HRR) and total heat release per unit area (THR) of PP composite follows the order AC-5Ni-Al-PP < AC-10Ni-Al-PP < AC-Ni-PP < AC-15Ni-Al-PP < AC-1Ni-Al-PP. Compared to the neat PP, the peak of HRR declined by 73.8%, 72.7%, 71.3%, 67.6% and 62.5%, respectively.

Application of Metal-Based Catalysts for Semi-Hydrogenation of Alkynol: A Review.

Alkynol semi-hydrogenation plays a vital role in industrial processes, due to the significance of its main product, enol, in high-end chemical synthesis, such as medicine, pesticide, food additives, and polymer monomer synthesis. Multiple intermediates are formed through a complex series of parallel or continuous reactions under varying conditions. However, the selectivity and efficiency of catalysts for producing these products still pose significant challenges. This review aims to thoroughly discuss the challenges and advancements in catalysts using different species and supports under various reaction conditions. Furthermore, strategies to enhance the yield and rate of enols are summarized based on noble metals, non-noble metals, and metal comparisons. By addressing diverse catalysts and reaction conditions, this review provides valuable insights into improving the semi-hydrogenation of acetylenic alcohols to enols.

Ion-Dipole Interaction Enabling Highly Efficient CsPbI3 Perovskite Indoor Photovoltaics.

Metal halide perovskites are ideal candidates for indoor photovoltaics (IPVs) because of their easy-to-adjust bandgaps, which can be designed to cover the spectrum of any artificial light source. However, the serious non-radiative carrier recombination under low light illumination restrains the application of perovskite-based IPVs (PIPVs). Herein, polar molecules of amino naphthalene sulfonates are employed to functionalize the TiO2 substrate, anchoring the CsPbI3 perovskite crystal grains with a strong ion-dipole interaction between the molecule-level polar interlayer and the ionic perovskite film. The resulting high-quality CsPbI3 films with the merit of defect-immunity and large shunt resistance under low light conditions enable the corresponding PIPVs with an indoor power conversion efficiency of up to 41.2% (Pin : 334.11 µW cm-2 , Pout : 137.66 µW cm-2 ) under illumination from a commonly used indoor light-emitting diode light source (2956 K, 1062 lux). Furthermore, the device also achieves efficiencies of 29.45% (Pout : 9.80 µW cm-2 ) and 32.54% (Pout : 54.34 µW cm-2 ) at 106 (Pin : 33.84 µW cm-2 ) and 522 lux (Pin : 168.21 µW cm-2 ), respectively.