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Abstract Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.

Abstract Radical substitution is a useful method to functionalize heterocycles, as in the venerable Minisci reaction. Empirically observed regiochemistries indicate that the CF2H radical has a nucleophilic character similar to alkyl radicals, but the CF3 radical is electrophilic. While the difference between •CH3 and •CF3 is well understood, the reason that one and two Fs make little difference but the third has a large effect is puzzling. DFT calculations with M06-2X both reproduce experimental selectivities and also lead to an explanation of this difference. Theoretical methods reveal how the F inductive withdrawal and conjugative donation alter radical properties, but only CF3 becomes decidedly electrophilic toward heterocycles. Here, we show a simple model to explain the radical orbital energy trends and resulting nucleophilicity or electrophilicity of fluorinated radicals.

Monitoring the actual surface deformation caused by subsurface fluid activities is crucial for comprehending the subsurface fluid mutation process. Incorporation of InSAR observations in a prior volume strain model can facilitate the estimation of subsurface fluid volumetric changes and three-dimensional (3-D) surface deformation. However, the model parameters, i.e., the thickness and depth of the subsurface fluid reservoir, are assumed to be known a priori. Therefore, it is impossible to acquire the precise model parameters in practice. Therefore, we proposed a novel approach for adaptive estimation of the model parameters by utilizing the black hole strategy method integrated with the particle swarm optimization algorithm. First, the performance of this method was tested through simulation experiments. The results suggest that the proposed method can precisely determine the model parameters and 3-D deformations of the subsurface fluids. Finally, the proposed model was tested using actual data from the Shale gas area in Texas and the Kilauea Caldera volcano in Hawaii, USA. For long-term, slow small deformations or sudden large deformations caused by the subsurface fluids, the proposed algorithm can obtain corresponding 3-D deformations, especially in the presence of incoherent regions, which can still obtain a complete 3-D deformation field.

Reasonable dense planting is an important measure to increase crop yield per unit area and save resources. However, there is no unified view of the competition for photosynthetic radiation in different stratification structures of maize plants due to different planting densities, as well as the internal mechanism of yield increase. In order to investigate these issues, field experiments were conducted from 2021 to 2022 in Daxing, Beijing, China (39°37′ N, 116°25′ E, altitude 31.3 m a.s.l.). Field plots were arranged in a randomized block design, with the main plot factor representing plant density. In each replicate, four densities were set, i.e., 33,000 (D1), 42,000 (D2), 55,000 (D3), and 83,000 (D4) plants·ha−1. Canopy stratification structure characteristics, including leaf area index, biomass, and photosynthetically active radiation (PAR), were measured in each stratification structure, and transmitted PAR, radiation use efficiency (RUE), and light extinction coefficient (K) were calculated. We found that increasing plant density significantly increased biomass, leaf area index (LAI), and precipitation use efficiency (PUE), but the light extinction coefficient (K) and harvest index (HI) showed opposite trends. Compared to the D1 treatment, the grain yield, precipitation use efficiency (PUE), radiation use efficiency (RUE), and LAI increased by 22.6–88.2%, 9.2–50.5%, 26.7–116.9%, and 27.7 to 150.6% in the D2, D3, and D4 treatments, and K and HI decreased by 19.7–50.3% and 4.2–11.5%, respectively. These showed that a density of 83,000 plants·ha−1 was effective in promoting maize growth in the Daxing area of Beijing, China.

Silver nanowires (AgNWs) deposited on plastic substrates show potential as electrodes for flexible electronics but face challenges due to high surface roughness and poor compatibility with organic plastics. To overcome these issues, this study incorporates calcium alginate, a cross-linked polymer binder, into the electrodes through the cross-linking of sodium alginate with calcium chloride. This method offers several advantages. Firstly, calcium alginate fills the gaps between AgNWs, reducing surface roughness. Additionally, Cl− ions aid in the welding of AgNW junctions, enhancing conductivity. Furthermore, the carboxylate and hydroxyl groups in calcium alginate establish robust interactions with both AgNWs and plastic substrates, bolstering electrode durability. The resulting electrodes exhibit favorable characteristics, including a reduced roughness of 8.4 nm, a low sheet resistance of 8.3 Ω cm−2, high transmittance (91.2% at 550 nm), and exceptional resistance to air, solvents, and mechanical stress. Consequently, flexible organic solar cells with these electrodes display superior mechanical resilience, maintaining over 96% of their initial power conversion efficiency (PCE) even when subjected to a small fixed bending radius of 1 mm for 1,000 cycles. Furthermore, these devices even experience less than an 8% PCE decrease after 10,000 bending cycles at a radius of 2.5 mm.

Abstract The upper mantle is heterogeneous in Fe isotope compositions, but the origin of the heterogeneity needs understanding. Recent studies on oceanic basalts demonstrate that the upper mantle Fe isotope heterogeneity results from low‐degree melt metasomatism. However, whether this hypothesis is of global significance needs testing in continental settings. Here we present an Fe isotopic study on intraplate continental alkali basalts from continental China, which are shown to have derived from upper mantle containing more metasomatized lithologies. The results show first‐order positive correlations of δ56Fe with indices of low‐degree melt metasomatism (e.g., [La/Sm]N), which, together with the so‐far published mid‐ocean ridge basalts data, define global trends, substantiating the global significance of low‐degree melt metasomatism in causing upper mantle Fe isotope variation. We, thus, suggest that low‐degree melt metasomatism is a globally effective process to preferentially concentrate heavy Fe isotopes in metasomatic lithologies at upper mantle conditions both today and in Earth's history.

Abstract Apolipoprotein A-I binding protein (AIBP), a secreted protein, has been shown to play a pivotal role in the development of atherosclerosis. The function of intracellular AIBP, however, is not yet well characterized. Here, we found that AIBP is abundantly expressed within human and mouse atherosclerotic lesions and exhibits a distinct localization in the inner membrane of mitochondria in macrophages. Bone marrow-specific AIBP deficiency promotes the progression of atherosclerosis and increases macrophage infiltration and inflammation in low-density lipoprotein receptor-deficient (LDLR−/−) mice. Specifically, the lack of mitochondrial AIBP leads to mitochondrial metabolic disorders, thereby reducing the formation of mitophagy by promoting the cleavage of PTEN-induced putative kinase 1 (PINK1). With the reduction in mitochondrial autophagy, macrophages polarize to the M1 proinflammatory phenotype, which further promotes the development of atherosclerosis. Based on these results, mitochondrial AIBP in macrophages performs an antiatherosclerotic role by regulating of PINK1-dependent mitophagy and M1/M2 polarization. Video Abstract

Synthetic Aperture Radar (SAR) interferometry is one of the most powerful remote sensing tools for ground deformation detection. However, tropospheric delay greatly limits the measurement accuracy of the InSAR technique. While vertically stratified tropospheric delays have been extensively investigated and well tackled, turbulent tropospheric phase noise still remains an intractable issue. In recent years, great efforts have been made to reduce the influence of turbulent atmospheric delay. This contribution is intended to provide a systematic review of the progress achieved in this field. First, it introduces the physical characteristics of atmospheric signals in interferograms. Then, a review of the main mitigation algorithms proposed in the literature is provided. In addition, the strengths and weaknesses of each approach are analyzed to provide guidance for choosing a suitable method accordingly. Finally, suggestions for resolving the challenging issues and an outlook for future research are given.

Aiming at the problem that is difficult to extract the fault features of gears under variable working and strong noise conditions，a fault diagnosis method based on adaptive time-varying filtering（ATF） and angle domain synchronous average（ASAD） is proposed. By combining ASAD and ATF，the signal after noise reduction is analyzed by order spectrum，and the local fault of gear can be diagnosed by modulation side frequency band in order spectrum. The simulation data and the data analysis of the variable speed gearbox test bench show that the proposed method has a good signal analysis adaptability for the gear vibration signals under the variable speed condition，and can not only filter out noise interference well，improve the noise suppression effect in the pass band，but also effectively highlight the gear fault characteristics under the variable speed condition.

Catalytic asymmetric dearomatization is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. Here the authors show an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition.

Summary: Obesity-prone or obesity-resistant phenotypes can exist in individuals who consume the same diet type. Brown adipose tissue functions to dissipate energy in response to cold exposure or overfeeding. Long noncoding RNAs play important roles in a wide range of biological processes. However, systematic examination of lncRNAs in phenotypically divergent mice has not yet been reported. Here, the lncRNA expression profiles in BAT of HFD-induced C57BL/6J mice were investigated by high-throughput RNA sequencing. Genes that play roles in thermogenesis and related pathways were identified. We found lncRNA (Gm44502) may play a thermogenic role in obesity resistance by interacting with six mRNAs. Our results also indicated that seven differentially expressed lncRNAs (4930528G23Rik, Gm39490, Gm5627, Gm15551, Gm16083, Gm36860, Gm42002) may play roles in reducing heat production in obesity susceptibility by interacting with seven differentially expressed mRNAs. The screened lncRNAs may participate in the pathogenesis of weight regulation and provide insight into obesity therapy.

AbstractBackground There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.Method In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.Results A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.Conclusions and relevance rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir–ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

The spatial-temporal baseline threshold method is commonly used to select interferograms for the Small BAseline Subset interferometric synthetic aperture radar (SBAS-InSAR) technique. However, this selection strategy is rather empirical and prone to including highly contaminated interferograms or excluding those with high quality. To overcome these limitations, this study first derives the relationship between the measurement accuracy of unknown parameters and the number of selected interferograms with their corresponding qualities. Subsequently, an adaptive interferogram selection method is proposed on the basis of Graph Theory (GT) and the turbulence atmospheric effects of interferogram. This proposed method first identifies and deletes the SAR image that is severely polluted by atmospheric phase. Second, high-quality interferograms are selected for SBAS-InSAR based on their corresponding turbulence atmospheric variance. Compared with the traditional selection method, this approach can significantly reduce the effect of turbulence atmosphere on SBAS-InSAR. A set of simulated experiments and real Sentinel-1A data in Hawaii, United States, validate the good performance of the proposed method.

Abstract Background CD8+ T cells differentiate into exhausted status within tumors, including hepatocellular carcinoma (HCC), which constitutes a solid barrier to effective anti-tumor immunity. A detailed characterization of exhausted T cells and their prognostic value in HCC is lacking. Methods We collected fresh tumor tissues with adjacent non-tumor liver tissues and blood specimens of 56 HCC patients, as well as archived samples from two independent cohorts of HCC patients (n = 358 and n = 254), who underwent surgical resection. Flow cytometry and multiplex immunostaining were used to characterize CD8+ T cells. Patient prognosis was evaluated by Kaplan-Meier analysis and Cox regression analysis. Results CD8+ T cells were classified into three distinct subpopulations: PD1Hi, PD1Int and PD1−. PD1Hi CD8+ T cells were significantly enriched in tumor compared to adjacent non-tumor liver tissues. PD1Hi CD8+ T cells highly expressed exhaustion-related inhibitory receptors (TIM3, CTLA-4, etc.) and transcription factors (Eomes, BATF, etc.). In addition, PD1Hi CD8+ T cells expressed low levels of cytotoxic molecules and displayed a compromised capacity to produce pro-inflammatory cytokines while the expression of anti-inflammatory IL-10 was up-regulated following mitotic stimulation. Furthermore, PD1Hi CD8+ T cells shared features with tissue resident memory T cells and were also characterized in an aberrantly activated status with an apoptosis-prone potential. In two independent cohorts of HCC patients (n = 358 and n = 254), we demonstrated that PD1Hi or TIM3+PD1Hi CD8+ T cells were significantly correlated with poor prognosis, and the latter was positioned in close proximity to PD-L1+ tumor associated macrophages. Conclusion The current study unveils the unique features of PD1Hi CD8+ exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies.

Fas signalling induces apoptosis of activated T cells to maintain immune homeostasis. Here the authors show that Fas also induces PKC-β activation to promote NF-κB-mediated TH9 cell differentiation, while p38 activation by PKC-β antagonizes this effect, thereby supporting a synergy between p38 inhibitor and Fas for TH9 differentiation.

Based on our previous work modeling crop growth (CropSPAC) and water and heat transfer in the soil-plant-atmosphere continuum (SPAC), the model was improved by considering the effect of plastic film mulching applied to field-grown maize in North-west China. In CropSPAC, a single layer canopy model and a multi-layer soil model were adopted to simulate the energy partition between the canopy and water and heat transfer in the soil, respectively. The maize growth module included photosynthesis, growth stage calculation, biomass accumulation, and participation. The CropSPAC model coupled the maize growth module and SPAC water and heat transfer module through leaf area index (LAI), plant height and soil moisture condition in the root zone. The LAI and plant height were calculated from the maize growth module and used as input for the SPAC water and heat transfer module, and the SPAC module output for soil water stress conditions used as an input for maize growth module. We used rs, the representation of evaporation resistance, instead of the commonly used evaporation resistance rs0 to reflect the change of latent heat flux of soil evaporation under film mulching as well as the induced change in energy partition. The model was tested in a maize field at Yingke irrigation area in North-west China. Results showed reasonable agreement between the simulations and measurements of LAI, above-ground biomass and soil water content. Compared with the original model, the modified model was more reliable for maize growth simulation under film mulching and showed better accuracy for the LAI (with the coefficient of determination R2 = 0.92, the root mean square of error RMSE= 1.23, and the Nush-Suttclife efficiency Ens = 0.87), the above-ground biomass (with R2 = 0.96, RMSE= 7.17 t·ha−1 and Ens = 0.95) and the soil water content in 0–1 m soil layer (with R2 = 0.78, RMSE= 49.44 mm and Ens = 0.26). Scenarios were considered to simulate the influence of future climate change and film mulching on crop growth, soil water and heat conditions, and crop yield. The simulations indicated that the change of LAI, leaf biomass and yield are negatively correlated with temperature change, but the growing degree-days, evaporation, soil water content and soil temperature are positively correlated with temperature change. With an increase in the ratio of film mulching area, the evaporation will decrease, while the impact of film mulching on crop transpiration is not significant. In general, film mulching is effective in saving water, preserving soil moisture, increasing soil surface temperature, shortening the potential growth period, and increasing the potential yield of maize.

Oral squamous cell carcinoma (OSCC) is a malignant tumour originating from the mucosal lining of the oral cavity. Its characteristics include hidden onset, high recurrence, and distant metastasis after operation. At present, clinical treatment usually includes surgery, chemotherapy, radiotherapy, or the joint use of these modalities. Unfortunately, multidrug resistant is one of the important obstacles that causes cancer chemotherapy failure. Anlotinib, which has recently been proven to have good antitumour effects, is a novel multitargeted tyrosine kinase inhibitor. However, there are few studies of the anlotinib-associated mechanism in OSCC and its underlying molecular mechanism. In our study, in vitro models of human oral squamous cell carcinoma HSC-3 cells were used to determine the efficacy of anlotinib. On the one hand, we showed that anlotinib treatment significantly reduced the viability and proliferation of HSC-3 cells and decreased cell migration by inhibiting the activation of the Akt phosphorylation pathway. On the other side, anlotinib inhibited PI3K/Akt/Bad phosphorylation and promoted apoptosis of HSC-3 cells by activating RAS protein expression. In brief, these results indicated that anlotinib had prominent antitumour activity in OSCC, mainly by inhibiting the PI3K/Akt phosphorylation pathway. This work provides evidences and a basic principle for using anlotinib to treat patients with OSCC for clinical research.

Abstract The single-phase CoMoO4 was prepared via a facile hydrothermal method coupled with calcination treatment at 400 °C. The structures, morphologies, and electrochemical properties of samples with different hydrothermal reaction times were investigated. The microsphere structure, which consisted of nanoflakes, was observed in samples. The specific capacitances at 1 A g−1 are 151, 182, 243, 384, and 186 F g−1 for samples with the hydrothermal times of 1, 4, 8, 12, and 24 h, respectively. In addition, the sample with the hydrothermal time of 12 h shows a good rate capability, and there is 45% retention of initial capacitance when the current density increases from 1 to 8 A g−1. The high retain capacitances of samples show the fine long-cycle stability after 1000 charge-discharge cycles at current density of 8 A g−1. The results indicate that CoMoO4 samples could be a choice of excellent electrode materials for supercapacitor.

Fe isotopes have been applied to the petrogenesis of ore deposits. However, the behavior of iron isotopes in the mineralization of porphyry-skarn deposits is still poorly understood. In this study, we report the Fe isotopes of ore mineral separations (magnetite, pyrite, chalcopyrite and pyrrhotite) from two different skarn deposits, i.e., the Tonglvshan Cu-Fe skarn deposit developed in an oxidized hydrothermal system and the Anqing Cu skarn deposit developed in a reduced hydrothermal system. In both deposits, the Fe isotopes of calculated equilibrium fluids are lighter than those of the intrusions responsible for the skarn and porphyry mineralization, corroborating the “light-Fe fluid” hypothesis. Interestingly, chalcopyrite in the oxidized-Tonglvshan skarn deposit has lighter Fe than chalcopyrite in the reduced-Anqing skarn deposit, which is best understood as the result of the prior precipitation of magnetite (heavy Fe) from the ore fluid in the oxidized-Tonglvshan systems and the prior precipitation of pyrrhotite (light Fe) from the ore fluid in the reduced-Anqing system. The δ56Fe for pyrite shows an inverse correlation with δ56Fe of magnetite in the Tonglvshan. In both deposits, the Fe isotope fractionation between chalcopyrite and pyrite is offset from the equilibrium line at 350 °C and lies between the FeS-chalcopyrite equilibrium line and pyrite-chalcopyrite equilibrium line at 350 °C. These observations are consistent with the FeS pathway towards pyrite formation. That is, Fe isotopes fractionation during pyrite formation depends on a path from the initial FeS-fluid equilibrium towards the pyrite-fluid equilibrium due to the increasing extent of Fe isotopic exchange with fluids. This finding, together with the data from other deposits, allows us to propose that the pathway effect of pyrite formation in the Porphyry-skarn deposit mineralization is the dominant mechanism that controls Fe isotope characteristics.

Many studies have shown that the average iron (Fe) isotope compositions of mantle-derived rocks, mantle peridotite and model mantle are close to those of chondrites. Therefore, it is considered that chondrite values represent the bulk Earth Fe isotope composition. However, this is a brave assumption because nearly 90% of Fe of the Earth is in the core, where its Fe isotope composition is unknown, but it is required to construct bulk Earth Fe isotope composition. We approach the problem by assuming that the Earth’s core separation can be approximated in terms of the Sudbury-type Ni-Cu sulfide mineralization, where sulfide-saturated mafic magmas segregate into immiscible sulfide liquid and silicate liquid. Their density/buoyancy controlled stratification and solidification produced net-textured ores above massive ores and below disseminated ores. The coexisting sulfide minerals (pyrrhotite (Po) > pentlandite (Pn) > chalcopyrite (Cp)) and silicate minerals (olivine (Ol) > orthopyroxene (Opx) > clinopyroxene (Cpx)) are expected to hold messages on Fe isotope fractionation between the two liquids before their solidification. We studied the net-textured ores of the Sudbury-type Jinchuan Ni-Cu sulfide deposit. The sulfide minerals show varying δ56Fe values (−1.37–−0.74‰ (Po) < 0.09–0.56‰ (Cp) < 0.53–1.05‰ (Pn)), but silicate minerals (Ol, Opx, and Cpx) have δ56Fe values close to chondrites (δ56Fe = −0.01 ± 0.01‰). The heavy δ56Fe value (0.52–0.60‰) of serpentines may reflect Fe isotopes exchange with the coexisting pyrrhotite with light δ56Fe. We obtained an equilibrium fractionation factor of Δ56Fesilicate-sulfide ≈ 0.51‰ between reconstructed silicate liquid (δ56Fe ≈ 0.21‰) and sulfide liquid (δ56Fe ≈ −0.30‰), or Δ56Fesilicate-sulfide ≈ 0.36‰ between the weighted mean bulk-silicate minerals (δ56Fe[0.70ol,0.25opx,0.05cpx] = 0.06‰) with weighted mean bulk-sulfide minerals (δ56Fe ≈ −0.30‰). Our study indicates that significant Fe isotope fractionation does take place between silicate and sulfide liquids during the Sudbury-type sulfide mineralization. We hypothesize that significant iron isotope fractionation must have taken place during core–mantle segregation, and the bulk Earth may have lighter Fe isotope composition than chondrites although Fe isotope analysis on experimental sulfide-silicate liquids produced under the varying mantle depth conditions is needed to test our results. We advocate the importance of further research on the subject. Given the close Fe-Ni association in the magmatic mineralization and the majority of the Earth’s Ni is also in the core, we infer that Ni isotope fractionation must also have taken place during the core separation that needs attention.

Abstract Background FOXP3 has been discovered to be expressed in tumor cells and participate in the regulation of tumor behavior. Herein, we investigated the clinical relevance and biological significance of FOXP3 expression in human hepatocellular carcinoma (HCC). Methods Expression profile of FOXP3 was analyzed using real-time RT-PCR, western blotting and immunofluorescence on HCC cell lines, and immunostaing of a tissue microarray containing of 240 primary HCC samples. The potential regulatory roles of FOXP3 were dissected by an integrated approach, combining biochemical assays, analysis of patient survival, genetic manipulation of HCC cell lines, mouse xenograft tumor models and chromatin immunoprecipitation (ChIP) sequencing. Results FOXP3 was constitutively expressed in HCC cells with the existence of splice variants (especially exon 3 and 4 deleted, Δ3,4-FOXP3). High expression of FOXP3 significantly correlated with low serum α-fetoprotein (AFP) level, absence of vascular invasion and early TNM stage. Survival analyses revealed that increased FOXP3 expression was significantly associated with better survival and reduced recurrence, and served as an independent prognosticator for HCC patients. Furthermore, FOXP3 could potently suppress the proliferation and invasion of HCC cells in vitro and reduce tumor growth in vivo. However, Δ3,4-FOXP3 showed a significant reduction in the tumor-inhibiting effect. The inhibition of FOXP3 on HCC aggressiveness was acted probably by enhancing the TGF-β/Smad2/3 signaling pathway. Conclusion Our findings suggest that FOXP3 suppresses tumor progression in HCC via TGF-β/Smad2/3 signaling pathway, highlighting the role of FOXP3 as a prognostic factor and novel target for an optimal therapy against this fatal malignancy.

Abstract Density functional M11 was used to study the mechanism and enantioselectivity of a binaphthophosphepine-catalyzed intramolecular [3 + 2] cycloaddition reaction. The computational results revealed that this reaction proceeds through nucleophilic addition of the phosphine catalyst to the allene, which yields a zwitterionic phosphonium intermediate. The subsequent stepwise [3 + 2] annulation process, which starts with the intramolecular nucleophilic addition of the allenoate moiety to the electron-deficient olefin group, determines the enantioselectivity of the reaction. This step is followed by a ring-closing reaction and water-assisted proton-transfer process to afford the final product with concomitant regeneration of the phosphine catalyst. Theoretical predictions of the enantioselectivity for various phosphine catalysts were consistent with experimental observations, and 2D contour maps played an important role in explaining the origin of the enantioselectivity. Moreover, on the basis of our theoretical study, new binaphthophosphepine catalysts were designed and that are expecting to afford higher enantioselectivity in this cycloaddition reaction.

As a major cellular component in tumor microenvironment, the distribution, frequency, and prognostic significance of infiltrating B cell subsets in hepatocellular carcinoma (HCC) remain controversial. Using tyramide signal amplification (TSA) based fluorescent multiplexed immunohistochemistry in situ, we evaluated the distribution and frequency of B cell subsets in two independent HCC cohorts (n = 619). The results were further confirmed by flow cytometry. Correlations of B cell subsets with clinicopathologic features and patient prognosis were analyzed. Five B cell subsets were defined by multiplexed immunohistochemistry and each subset was clearly separated by t-SNE dimension reduction analysis. Notably, the densities of all B cell subsets were significantly decreased in the tumor. The frequency of plasma cells within B cells was most abundant in the tumor. In training cohort (n = 258), high densities of tumor-infiltrating CD20+ B cells, naive B cells, IgM+ memory B cells, CD27− isotype-switched memory B cells, and plasma cells were associated with superior survival. Multivariate analysis further identified CD20+ B cells, naive B cells, and CD27− isotype-switched memory B cells as independent prognosticators for survival. Unsupervised cluster analysis confirmed increased B cell subsets harbored superior survival. In addition, high density of B cells was correlated with smaller tumor size and well differentiation. The results were validated in the independent cohort of 361 HCC patients. Intratumor infiltration of B cells is significantly impaired during HCC progression. High densities of tumor-infiltrating B cells imply a better clinical outcome. Therapies designed to target B cells may be a novel strategy in HCC.

For nanometer MOSFETs, charging and discharging a single trap induces random telegraph noise (RTN). When there are more than a few traps, RTN signal becomes complex and appears as within a device fluctuation (WDF). RTN/WDF causes jitters in switch timing and is a major challenge to low power circuits. In addition to RTN/WDF, devices also age. The interaction between RTN/WDF and aging is of importance and not fully understood. Some researchers reported aging increasing RTN/WDF, while others showed RTN/WDF being hardly affected by aging. The objective of this paper is to investigate the impact of hot carrier aging (HCA) on the RTN/WDF of nMOSFETs. For devices of average RTN/WDF, it is found that the effect of HCA is generally modest. For devices of abnormally high RTN/WDF, however, for the first time, we report HCA reducing RTN/WDF substantially (>50%). This reduction originates from either a change of current distribution or defect losses.

Time series of ground subsidence can not only be used to describe motion produced by various anthropocentric and natural process but also to better understand the processes and mechanisms of geohazards and to formulate effective protective measures. For high-accuracy measurement of small baseline subset interferometric synthetic aperture radar (SBAS-InSAR), atmospheric turbulence and decorrelation noise are regarded as random variables and cannot be accurately estimated by a deterministic model when large spatio-temporal variability presents itself. Various weighting methods have been proposed and improved continuously to reduce the effects of these two parts and provide uncertainty information of the estimated parameters, simultaneously. Network-based variance-covariance estimation (NVCE) and graph theory (GT) are the two main weighting methods which were developed on the basis of previous algorithms. However, the NVCE weighting method only focuses on the influence of atmospheric turbulence and neglects the decorrelation noise. The GT method weights each interferogram in a time series by using the Laplace transformation. Although simple to implement, it is not reasonable to have an equal weight for each pixel in the same interferogram. To avoid these limitations, this study presents a new weighting method by considering the physical characteristics of atmospheric turbulence and decorrelation noise in SBAS-InSAR images. The effectiveness of the proposed method was tested and validated by using a set of simulated experiments and a case study on a Hawaiian island. According to the GPS-derived displacements, the average RMSE of the results from the new weighting method was 1.66 cm, indicating about an 8% improvement compared with 1.79, 1.80 and 1.80 cm from the unweighted method, the NVCE method and the GT method, respectively.

Dual-driving systems have been widely adopted in advanced manufacturing machine. Synchronization of the dual-servo systems is crucial for tracking reference trajectories. This article proposes a novel cross-coupled fuzzy logic sliding mode control for the synchronous control of dual-driving feed system. The dynamic model of dual-driving system has been established and the individual proportional–proportional–integral controller is built based on the dynamic model. To increase the synchronous performance, a cross-coupled sliding mode controller is provided based on dual-driving system model. In addition, a continuous saturation function is adopted to reduce chattering. Lyapunov stability criterion is used to analyze the stability of the cross-coupled sliding mode control. Moreover, a fuzzy logic saturation gain control approach is proposed to overcome the low robustness and poor dynamic synchronous performance in the normal cross-coupled control scheme. The adaptive saturation function is designed to eliminate synchronous deviation caused by the process of two axes following each other. Finally, an industrial application of dual-driving system is utilized to prove the effectiveness of the proposed scheme. The proposed cross-coupled fuzzy logic sliding mode control scheme has been effectively demonstrated to improve synchronous performance and tracking accuracy.

It is of great significance to study the dynamic characteristics of twin ball screw (TBS) feed system to improve the precision of gantry-type dual-driven computer numerical control (CNC) machine tools. In this paper, an equivalent dynamic model of the TBS feed system is established utilizing lumped mass method considering the stiffness of joints. Equivalent axial stiffness of screw-nut joints and bearing joints are both calculated by Hertz contact theory. Furthermore, a friction model is proposed because the friction force of the screw nut affects the stiffness of the joints. Then, the friction parameters are obtained by using the nonlinear system identification method. Meanwhile, a finite element model (FEM) is developed to assess the dynamic characteristics of TBS feed system under the stiffness of joints. Finally, validation experiments are conducted, and the results show that the positions of the nut and the velocities of worktable greatly affect the dynamic characteristics of the TBS feed system. Compared with the theoretical calculation, FEM and experiments indicate that the dynamic modeling proposed in this article can reach a higher accuracy.

The phase constitutions of as-cast magnesium (Mg)-Zn-Gd alloys (Zn/Gd = 0.25~60, Zn 0~10 at.%, Gd 0~2 at.%, 48 samples) were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The Mg-Zn-Gd phase diagram focused on the Mg-rich corner (with up to 20 at.% Zn, 10 at.% Gd) has been set up. Five regions can be classified as follows: (I) α-Mg+W-phase+(binary compounds), (II) α-Mg+W-phase+I-phase(+binary compounds), (III) α-Mg+I-phase(+binary compounds), (IV) α-Mg+binary compounds, and (V) α-Mg. The phase diagram has been verified by solidification behaviors observation using differential thermal analysis (DTA). Moreover, the structures of I-phase and W-phase in the alloy were explored in details. In terms of the Hume-Rothery rules, I-phase is confirmed as FK-type quasicrystalline with a chemical stoichiometry as Mg30±1Zn62Gd8±1 (at.%). The composition and lattice parameter a W-phase (fcc structure, m3¯m) are affected by the composition of Mg-Zn-Gd alloys, especially by the Zn/Gd ratio of alloys. This work would be instructive for the design of Mg-Zn-Gd alloys to obtain the phase components, and then selected the strengthening ways, which could adjust its mechanical properties.

Metastasis accounts for the most deaths in patients with hepatocellular carcinoma (HCC). Receptor activator of nuclear factor kappa B ligand (RANKL) is associated with cancer metastasis, while its role in HCC remains largely unknown.Immunohistochemistry was performed to determine the expression of RANK in HCC tissue (n = 398). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to examine the expression of RANK, E-cadherin, N-cadherin, vimentin, Snail, Slug, Twist and MMPs in HCC cells. Wound healing and Transwell assays were used to evaluate cell migration and invasion ability.We found that expression of RANK, the receptor of RANKL, was significantly higher in HCC tumor tissues than in peritumor liver tissues (p