Global surface temperature short‐term trends fluctuate between cooling and fast‐warming under the combined action of external forcing and internal variability, significantly influencing the ...detectability of near‐term climate change. A key driver of these variations is anthropogenic aerosols (AAs), which have undergone a non‐monotonic evolution with rapid reduction in recent decades. However, their reduction is projected to decelerate under a high carbon emission scenario, yet the impact on surface temperature trends remains unknown. Here, using initial‐perturbation large ensembles, we find that future slowdown in AA reduction over Europe and North America expedites the subpolar North Atlantic surface warming by intensifying the Atlantic meridional overturning circulation. Further, it accelerates the South Indian Ocean and Southern Ocean surface warming through positive low‐cloud feedback and oceanic dynamical adjustment, triggered by the poleward migration of westerlies under interhemispheric energy constraint. These AA‐driven warmings exacerbate greenhouse warming, significantly enhancing the detectability of local decadal warming trends.
Plain Language Summary
Global surface temperature rises non‐monotonically, exhibiting phases of accelerated warming, warming slowdown, and transitions between warming and cooling. Anthropogenic aerosols (AAs) are a key driver of historical trend variations, making human‐induced trends more detectable. However, AAs follow a nonlinear trajectory with a rapid decline over Europe and North America in recent decades, and such reduction is projected to slow down in the future. The saturation of AA reduction signifies a diminishing proportion of anthropogenic forcings, which were previously considered unrelated to future global warming. Nevertheless, based on large ensembles of climate change simulations, we reveal that this projected slowdown in AA reduction could significantly accelerate surface warming in the subpolar North Atlantic, South Indian and Southern Oceans. This is achieved by the strengthening of Atlantic meridional overturning circulation and the coupled oceanic‐atmospheric adjustments triggered by the southward shift of southern westerlies. Those AA‐driven ocean surface warmings exacerbate greenhouse warming, significantly enhancing the predominance of external signals over strong internal noise and thus the detectability of regional human‐induced decadal warming trends. It suggests that upholding stringent AA mitigation policies is imperative for effectively mitigating the risk of severe ocean warming.
Key Points
Recent rapid reduction of anthropogenic aerosols (AA) over the northern extratropics would slow down under a high carbon emission scenario
Slower AA reduction accelerates subpolar North Atlantic surface warming by intensifying Atlantic meridional overturning circulation
Slower AA reduction accelerates South Indian and Southern Ocean warming via positive low‐cloud feedback and oceanic dynamical adjustment
Thermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation ...remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic changes of phenotype and function of NK cells in peripheral blood before and after thermal ablation of hepatitis B-associated HCC and their correlation with tumor recurrence.
Fifty-six patients clinically and pathologically confirmed with hepatitis B-associated HCC were selected for thermal ablation. Peripheral blood was collected on day 0, day 7, and month 1. NK cell subsets, receptors, and killing function were detected by flow cytometry, and the LDH levels were examined. Overall recurrence and associated variables were estimated using Kaplan-Meier, log-rank, and Cox proportional-hazards analyses.
The frequency of CD3
CD56
cells was increased on day 7 (P < 0.01) without significant differences between D0 and M1. NKG2D, NKp44, NKp30, CD159a, and CD158a expression was increased on M1 (all P < 0.05). The granzyme B and IFN-γ expression in NK cells were higher on M1 vs. D0 (P < 0.05). On day 7, the NK cell lysis activity of the target K562 cells was increased (P < 0.01) but decreased on M1 (P < 0.05). Survival analysis showed that CD158a expression and IFN-γ and perforin release on day 0 were associated with the risk of HCC recurrence. Cox regression analysis showed that the expression changes in CD56, NKp46, granzyme B, and perforin (D7-D0) induced by thermal ablation were associated with recurrence-free survival (RFS) of patients with HCC.
Thermal ablation increased the frequency and function of CD3
CD56
NK cells in the peripheral blood of patients with HCC. These cells tended to be more differentiated and activated. Notably, expression levels of NK cell receptors NKp46, perforin, and granzyme B were associated with RFS.
Conductive polymer composites (CPCs) have attracted much attention in strain sensing applications due to their excellent conductivities and high sensitivities. However, research on simultaneous ...modification of CPCs with multiple conductive fillers is lacking. This study aims to systematically investigate the electrical conductivities and strain‐sensing properties of two filler‐modified epoxy resin (EP) composites with different scale additives—short carbon fibers (SCFs) and carbon nanotubes (CNTs)—obtained by mixing and curing to obtain the samples. Both the SCF/EP and SCF/CNT/EP composite resistivities decreased with increasing filler content, and 1.35 wt% was the percolation threshold for SCF/EP composites; during monotonic tensile loading, the resistance change ratio (ΔR/R0) of the CPCs increased with increasing strain, and the sensitivities decreased with increasing conductive filler content. The CPCs containing SCFs and CNTs exhibited stable and repeatable resistance responses during cyclic tensile loading, among which the SCF/CNT_1.5/0.3 composite was the most suitable for use as a sensing material with a sensitivity of 0.149. According to the conductivity and resistance–strain response mechanism analysis, the CNTs supplementing and refining the CPC conductive network composed of SCFs were considered the main reason for the resistance response linearization and excellent dynamic response repeatability. CPCs can be widely used in strain sensing and damage monitoring.
Highlights
Provided a strategy for multiscale conductive filler‐modified epoxy resins.
Realized monotonicity of resistance–strain response by adding multiscale conductive fillers.
Explored resistance‐strain effect under dynamic cycling loading.
Identified optimal materials for damage detection.
Analyzed the resistance–strain response mechanism of single and multiscale conductive filler‐modified CPCs.
Preparation process, resistance–strain responses and schematic illustration of conductive networks of CPCs.
Background
Identification of activated epidermal growth factor receptor (EGFR) mutations and application of EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs) have greatly changed the therapeutic strategies ...of non‐small‐cell lung cancer (NSCLC). However, the long‐term efficacy of EGFR‐TKI therapy is limited due to the development of drug resistance. The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR‐TKIs in advanced NSCLC patients with activated EGFR mutations.
Methods
We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR‐TKI treatment, from April 2004 and March 2011, at the Sun Yat‐sen University Cancer Center. Several genetic alterations associated with the efficacy of EGFR‐TKIs, including the alterations in BIM, ALK, KRAS, PIK3CA, PTEN, MET, IGF1R, and ROS1, were detected by the routine clinical technologies. The progression‐free survival (PFS) and overall survival (OS) were compared between different groups using Kaplan–Meier survival analysis with the log‐rank test. A Cox regression model was used to estimate multivariable‐adjusted hazard ratios (HRs) and their 95% confidence intervals (95% CIs) associated with the PFS and OS.
Results
Among the investigated patients, 169 NSCLC patients harbored EGFR‐sensitive mutations. EGFR‐mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN (P = 0.003 for PFS, and P = 0.034 for OS). In the combined molecular analysis of EGFR signaling pathway and resistance genes, we found that EGFR‐mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations (P < 0.001). A Cox proportional regression model determined that PTEN deletion (HR = 4.29,95% CI = 1.72–10.70) and low PTEN expression (HR = 1.96, 95% CI = 1.22–3.13), MET FISH + (HR = 2.83,95% CI = 1.37–5.86) were independent predictors for PFS in patients with EGFR‐TKI treatment after adjustment for multiple factor.
Conclusions
We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR‐TKIs.
An ultrasensitive split-type fluorescent immunobiosensor has been reported based on a cascade signal amplification strategy by coupling chemical redox-cycling and Fenton-like reaction. In this ...strategy, Cu2+ could oxidize chemically o-phenylenediamine (OPD) to generate photosensitive 2, 3-diaminophenazine (DAP) and Cu+/Cu0. On one hand, the generated Cu0 in turn catalyzed the oxidation of OPD. On the other hand, the introduced H2O2 reacted with Cu + ion to produce hydroxyl radicals (·OH) and Cu2+ ion through a Cu + -mediated Fenton-like reaction. The produced ·OH and recycled Cu2+ ion could take turns oxidizing OPD to generate more photoactive DAP, which triggering a self-sustaining chemical redox-cycling reaction and leading to a remarkable fluorescent improvement. It was worth mentioning that the cascade reaction did not stop until OPD molecules were completely consumed. Based on the H2O2-triggered cascade signal amplification, the strategy was exploited for the construction of split-type fluorescent immunoassay by taking interleukin-6 (IL-6) as the model target. It was realized for the ultrasensitive determination of IL-6 in a linear ranging from 20 fg/mL to 10 pg/mL with a limit of detection of 5 fg/mL. The study validated the practicability of the cascade signal amplification on the fluorescent bioanalysis and the superior performance in fluorescent immunoassay. It is expected that the strategy would offer new opportunities to develop ultrasensitive fluorescent methods for biosensor and bioanalysis.
An ultrasensitive split-type fluorescent immunobiosensor has been reported for IL-6 detection based on a cascade signal amplification strategy by coupling chemical redox-cycling and Fenton-like reaction. Display omitted
•An ultrasensitive fluorescent immunoassay was realized by signal amplification.•The split-type immunoassay dramatically minimized the background interferences.•The sensitivity was improved by over 2-3 orders of magnitude than that of ELISA.•The strategy was coupled with chemical redox-cycling and Fenton-like reaction.
The application of 7‐indolylmethanols in catalytic asymmetric reactions has been established via an enantioselective arylation reaction with tryptamines in the presence of chiral phosphoric acid, ...which afforded a series of structurally diversified chiral 7‐indolylmethanes in moderate to good yields and generally excellent enantioselectivities (23 examples, up to 92% ee). This reaction not only provides a useful strategy for the enantioselective synthesis of chiral 7‐indolylmethanes, but also represents a good example of 7‐indolylmethanol‐involved catalytic asymmetric reaction, which will greatly enrich the chemistry of indolylmethanols.
Luteolin is a flavonoid compound derived from Lonicera japonica Thunb, which has been reported to exert anticancer effects on different types of tumors. miRNAs are a kind of endogenous non-coding ...small RNAs, which involved in occurrence and development of multi cancer, including miR-34a. However, the relationship between miR-34a and luteolin's susceptibility to cancer cells still remains unclear. In this study, we explored the roles of miR-34a and the effects of luteolin on GC cells as well as the underlying mechanism of miR-34a in mediating the susceptibility of GC cell to luteolin. Retrospectively study revealed that miR-34a expression was downregulated in human primary GC tissues compared with non-tumor tissues and low miR-34a expression was associated with a significantly shorter overall survival and disease-free survival. MiR-34a overexpression could inhibit GC cells and induce G1 phase arrest via p53/p21 and MAPK /ERK pathways. Luteolin decreased viability of GC cells in a dose-dependent manner. Meanwhile, miR-34a was found to be markedly upregulated in GC cells induced by luteolin and decreased miR-34a level was found in the artificial luteolin-resistant GC cells. Upregulation of miR-34a in luteolin-resistant GC cell could enhance the sensibility of GC cells to luteolin. On the other hand, miR-34a inhibitor could partly counter the anticancer effect of luteolin. In a further assay, we also found that targeting miR-34a could mediate the susceptibility of mouse xenografts to luteolin. Subsequent study found that HK1 was a direct target of miR-34a and downregulated HK1 mRNA or protein levels were presented after miRNA-34a overexpression in GC cells. Moreover, HK1 protein levels was decreased after luteolin treatment and partly restored when co-treated with luteolin and miR-34a inhibitor. Downregulation of HK1 in luteolin-resistant GC cell could increase the cell's sensitivity to luteolin. Therefore, our findings firstly suggested that miR-34a could modulate the susceptibility of gastric cancer cell to luteolin via targeting HK1, potentially benefiting GC patients' treatment in the future.
•miRNA-34a is down-regulated in human GC tissues and cell lines.•miRNA-34a can function as a suppressor in GC cells.•HK1 is a direct target of miRNA-34a.•miRNA-34a could mediate the susceptibility of GC cell to luteolin in vitro and in vivo.•miRNA-34a could mediate the susceptibility of GC cell to luteolin by targeting HK1.
A detailed model of soot formation is proposed, which consists of a gas-phase kinetic model for the pyrolysis and oxidation of selected hydrocarbon fuels and a kinetic mechanism of soot nucleation ...and mass/size growth through coagulation and surface reactions. The gas-phase model (Ranzi et al., 2012) was expanded to include the chemistry of Polycyclic Aromatic Hydrocarbons (PAHs) up to four-to-five ring PAHs, with a modular and hierarchical approach. The discrete sectional method was employed to solve the size evolution of the particle size distribution function (PSDF). Analogy and similarity rules were employed to describe heterogeneous reaction kinetics of soot surface reactions. A variable collision efficiency was assumed for the coalescence of small soot particles. Larger particles were assumed to undergo aggregation. The predicted PSDFs are found to be in reasonably good agreement with the experimental data for nascent soot measured in an atmospheric-pressure premixed ethylene–oxygen–argon flame in the burner-stabilized stagnation flame configuration. Sensitivity analyses of the PSDF, number density, and volume fraction were carried out with respect to the rate parameters of addition reactions of acetylene, PAHs, resonantly stabilized radical reactions, and coalescence and aggregation. The results show that the reaction of PAHs and acetylene with soot surfaces and the kinetics of coalescence and aggregation exhibit dominant effects on the detailed and global soot properties for the flame studied, in agreement with conclusions of a large range of previous modeling studies.
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