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Programmed cell death protein 1 (PD-1) ligation delimits immunogenic responses in T cells. However, the consequences of programmed cell death 1 ligand 1 (PD-L1) ligation in T cells are uncertain. We found that T cell expression of PD-L1 in cancer was regulated by tumor antigen and sterile inflammatory cues. PD-L1 + T cells exerted tumor-promoting tolerance via three distinct mechanisms: (1) binding of PD-L1 induced STAT3-dependent ‘back-signaling’ in CD4 + T cells, which prevented activation, reduced T H 1-polarization and directed T H 17-differentiation. PD-L1 signaling also induced an anergic T-bet − IFN-γ − phenotype in CD8 + T cells and was equally suppressive compared to PD-1 signaling; (2) PD-L1 + T cells restrained effector T cells via the canonical PD-L1–PD-1 axis and were sufficient to accelerate tumorigenesis, even in the absence of endogenous PD-L1; (3) PD-L1 + T cells engaged PD-1 + macrophages, inducing an alternative M2-like program, which had crippling effects on adaptive antitumor immunity. Collectively, we demonstrate that PD-L1 + T cells have diverse tolerogenic effects on tumor immunity. PD-L1 on tumor cells exerts an important dampening effect on T cells via their expression of PD-1. Miller and colleagues find that PD-L1 ‘back-signaling’ into T cells and macrophages can also dampen immune responses within the tumor microenvironment.

Organofluorine compounds have shown their great value in many aspects. Moreover, allenes are also a class of important compounds. Fluorinated or fluoroalkylated allenes might provide an option as candidates for drug and material developments, as allenes allow a great number of valuable transformations. Herein, we report a metal-free synthesis of difluoromethylated allenes via regioselective trifunctionalization of 1,3-enynes. This method proceeds through double C–F bond formation with concomitant introduction of an amino group to the allene. Synthetic applications are conducted and preliminary mechanistic studies suggest that a two-step pathway is involved. DFT calculations revealed an unusual dibenzenesulfonimide-assisted fluorination/fluoroamination with NFSI. In addition, kinetic reaction study revealed the induction period of both major and side products to support the proposed reaction mechanism. This work offers a convenient approach for the synthesis of a range of difluoromethylated allenes and is also a rare example of trifunctionalization of 1,3-enynes. Fluorinated or fluoroalkylated allenes are versatile building blocks for medicinal and material chemistry. Here, the authors show a regioselective trifunctionalization of 1,3-enynes proceeding through double C-F bond formation and concomitant installation of a -NSO 2 Ph group to the allene moiety.

This paper examines the impact on Factor of Safety (FS) value due to the variation in distributed load (L D ), Crest length (C L ), shear strength (τ), and shear stress (σ) both in seismic and non-seismic conditions. The main purpose of this paper is to develop correlations between these parameters, which can be used in any slope stability analysis design project. Forty number of analyses are performed by considering different soil material properties. Slope stability analysis is performed using Slide software and correlations are developed using Statistical Package for Social Sciences (SPSS) software as well as with the help of Microsoft Excel. The analysis results indicate that the seismic slope stability analysis gives optimum value for slope FS and therefore it is highly recommended to perform and give preference to seismic slope stability analysis of any soil slope to compute and recommend FS value. The main novelty of this paper are the eight new correlations. These correlations can be used in slope stability projects like earthfill dams design, embankments, or any slope design project or case study to know about the slope factor of safety in detail.

Abstract Glaciers in high-altitude mountain regions are retreating rapidly due to global warming, exposing deglaciated soils to extreme environmental conditions, and microbial colonization. However, knowledge about chemolithoautotrophic microbes, which play important roles in the development of oligotrophic deglaciated soils prior to plant colonization, remains elusive in deglaciated soils. Using real-time quantitative PCR and clone library methods, the diversity and succession of the chemolithoautotrophic microbial community harboring the cbbM gene across a 14-year deglaciation chronosequence on the Tibetan Plateau were determined. The abundance of the cbbM gene remained stable for the first 8 years after deglaciation and then increased significantly, ranging from 105 to 107 gene copies g−1 soil (P < 0.001). Soil total carbon increased gradually to 5-year deglaciation and then decreased. While total nitrogen and total sulfur levels were low throughout the chronosequence. Chemolithoautotrophs were related to Gammaproteobacteria and Betaproteobacteria, with the former dominating early deglaciated soils and the latter dominating older deglaciated soils. The diversity of chemolithoautotrophs was high in mid-age deglaciated soils (6-year-old) and was low in early (3-year-old) and older deglaciated soils (12-year-old). Our findings revealed that chemolithoautotrophic microbes colonize deglaciated soils quickly and follow a clear successional pattern across recently deglaciated chronosequences. Chemolithoautotrophic microbes colonize deglaciated soils quickly and follow a clear successional pattern across recently deglaciated chronosequences.

Assessment and analysis of soil slope stability is an important part of geotechnical engineering at all times. This paper examines the assessment of soil slope stability in fine-grained soils. The effect of change in shear strength (τ), shear stress (σ) and slope angle (β) on the factor of safety has been studied. It correlates shear strength with slope angle and shear stress by considering the horizontal seismic coefficients in both saturated and unsaturated conditions. The slope failure surface was considered a circular slip surface. Statistical package for social sciences (SPSS) and Slide, numerical modeling software and limit equilibrium slope stability analysis software, respectively, are used to find out the correlations between the three basic parameters. The slope angle varied from 70 to 88 degrees, which are the most critical values for slope angles, and a total of 200 analyses were performed. τ, β and σ are correlated, and the correlations are provided in the results section. The results indicate that the correlations developed between the parameters have a very close relationship. The applicability of the developed equations is above 99%. These correlations are applicable in any type of soil slope stability analysis, where the value of shear strength and factor of safety is required with the variation of slope angle and shear stress.

With the increase in iron/steel production, the higher volume of by-products (slag) generated necessitates its efficient recycling. Because the Linz-Donawitz (LD) slag is rich in silicon (Si) and other fertilizer components, we aim to evaluate the impact of the LD slag amendment on soil quality (by measuring soil physicochemical and biological properties), plant nutrient uptake, and strengthens correlations between nutrient uptake and soil bacterial communities. We used 16 S rRNA illumine sequencing to study soil bacterial community and APIZYM assay to study soil enzymes involved in C, N, and P cycling. The LD slag was applied at 2 Mg ha −1 to Japonica and Indica rice cultivated under flooded conditions. The LD slag amendment significantly improved soil pH, plant photosynthesis, soil nutrient availability, and the crop yield, irrespective of cultivars. It significantly increased N, P, and Si uptake of rice straw. The slag amendment enhanced soil microbial biomass, soil enzyme activities and enriched certain bacterial taxa featuring copiotrophic lifestyles and having the potential role for ecosystem services provided to the benefit of the plant. The study evidenced that the short-term LD slag amendment in rice cropping systems is useful to improve soil physicochemical and biological status, and the crop yield.

We investigate the dynamical behavior of a modified Leslie–Gower prey–predator model with harvesting in prey population. In order to explore rich dynamics of the model, Euler approximation is implemented to obtain a discrete-time modified Leslie–Gower model. Existence of equilibria and their local asymptotic stabilities are carried out. Furthermore, with the help of bifurcation theory and center manifold theorem, existence and directions of period-doubling and Neimark–Sacker bifurcations are investigated at positive steady-state. In order to control chaos and bifurcations, the Ott–Grebogi–Yorke (OGY) method and the hybrid control strategy are introduced. Numerical simulations are also provided to illustrate the theoretical discussions.

In this research, eight local mung bean ( Vigna radiata ) varieties were analyzed for their performance against two levels of CdCl 2 solution (0.3 and 0.5 mM) alone and priming with gibberellic acid (GA 3 ) (100 μM), salicylic acid (SA) (50 μM) and proline (5 mM) solution prior to Cd exposure. Mung bean seedlings were analyzed for disturbance in cytological, morphological, biochemical and enzymatic parameters under cadmium stress. For cytological studies, 48 h grown mung bean seedlings root tips were used to prepare slides and studied for percent mitotic index (MI%) and to calculate percent C-mitosis, laggard, sticky and fragmented chromosomes, pictures were captured by a Nikon camera (DS-Fi 1 Japan) attached with a microscope. One-week grown mung seedlings were studied for growth traits, malondialdehyde (MDA), protein, proline and antioxidant enzymes. ANOVA and DMR test of this research revealed that all the tested mung bean varieties and treatments were significantly different regarding mitotic index and number of chromosomal aberrations. Both the Cd treatments exhibited increased total chromosomal aberrations with different types and a maximum decrease in MI%. In pretreated samples, GA 3 , SA and proline serve as mitigating agents that reduce mutagenic effects of Cd in mung bean by increasing MI% and decreasing chromosomal aberrations as compared to non-pretreated samples. Both the Cd treatments showed a decrease in all growth traits. Total proteins were also found to be significantly reduced in a dose-dependent manner in all genotypes. Cd treatment increased the activities of all antioxidant enzymes tested. Cd caused oxidative damage as indicated by elevated levels of MDA content in treated samples in comparison to control. Proline content levels were also high in Cd treated seedlings indicating stress. Results demonstrated that pretreatment with phytohormones and proline before Cd were found to improve all morphological parameters, by altering antioxidant enzymes activities along with a decrease in MDA and proline contents as well. It was further noticed that the performance of GA 3 was better at 0.3 mM Cd treatment while SA was found to be a good mitigating agent at 0.5 mM Cd stress in all tested mung bean varieties. This research concluded less deleterious effects of Cd on AZRI-2006 while more sensitivity to NM-51 towards Cd. Priming with phytohormones and proline is a user-friendly, economical, and simple mitigation strategy to reduce Cd toxicity in plants and get better yield from contaminated lands.

Sparsity-driven regularization has undergone significant development in single-image restoration, particularly with the transition from handcrafted priors to trainable deep architectures. In this work, a geometric prior-enhanced deep image prior (DIP) framework, termed DIP-MC, is proposed that integrates mean curvature (MC) regularization to promote natural smoothness and structural coherence in reconstructed images. To strengthen the representational capacity of DIP, a self-attention module is incorporated between the encoder and decoder, enabling the network to capture long-range dependencies and preserve fine-scale textures. In contrast to total variation (TV), which frequently produces piecewise-constant artifacts and staircasing, MC regularization leverages curvature information, resulting in smoother transitions while maintaining sharp structural boundaries. DIP-MC is evaluated on standard grayscale and color image denoising and deblurring tasks using benchmark datasets including BSD68, Classic5, LIVE1, Set5, Set12, Set14, and the Levin dataset. Quantitative performance is assessed using peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) metrics. Experimental results demonstrate that DIP-MC consistently outperformed the DIP-TV baseline with 26.49 PSNR and 0.9 SSIM. It achieved competitive performance relative to BM3D and EPLL models with 28.6 PSNR and 0.87 SSIM while producing visually more natural reconstructions with improved detail fidelity. Furthermore, the learning dynamics of DIP-MC are analyzed by examining update-cost behavior during optimization, visualizing the best-performing network weights, and monitoring PSNR and SSIM progression across training epochs. These evaluations indicate that DIP-MC exhibits superior stability and convergence characteristics. Overall, DIP-MC establishes itself as a robust, scalable, and geometrically informed framework for high-quality single-image restoration.

Liver fibrosis and fibrosis-associated hepatocarcinogenesis are driven by chronic inflammation and are leading causes of morbidity and death worldwide. SYK signaling regulates critical processes in innate and adaptive immunity, as well as parenchymal cells. We discovered high SYK expression in the parenchymal hepatocyte, hepatic stellate cell (HSC), and the inflammatory compartments in the fibrotic liver. We postulated that targeting SYK would mitigate hepatic fibrosis and oncogenic progression. We found that inhibition of SYK with the selective small molecule inhibitors Piceatannol and PRT062607 markedly protected against toxin-induced hepatic fibrosis, associated hepatocellular injury and intra-hepatic inflammation, and hepatocarcinogenesis. SYK inhibition resulted in increased intra-tumoral expression of the p16 and p53 but decreased expression of Bcl-xL and SMAD4. Further, hepatic expression of genes regulating angiogenesis, apoptosis, cell cycle regulation, and cellular senescence were affected by targeting SYK. We found that SYK inhibition mitigated both HSC trans-differentiation and acquisition of an inflammatory phenotype in T cells, B cells, and myeloid cells. However, in vivo experiments employing selective targeted deletion of SYK indicated that only SYK deletion in the myeloid compartment was sufficient to confer protection against fibrogenic progression. Targeting SYK promoted myeloid cell differentiation into hepato-protective TNFα low CD206 hi phenotype downregulating mTOR, IL-8 signaling and oxidative phosphorylation. Collectively, these data suggest that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis.