Due to ultra-high reactivity, direct determination of free radicals, especially hydroxyl radical (•OH) with ultra-short lifetime, by field-effect transistor (FET) sensors remains a challenge, which ...hampers evaluating the role that free radical plays in physiological and pathological processes. Here, we develop a •OH FET sensor with a graphene channel functionalized by metal ion indicators. At the electrolyte/graphene interface, highly reactive •OH cuts the cysteamine to release the metal ions, resulting in surface charge de-doping and a current response. By this inner-cutting strategy, the •OH is selectively detected with a concentration down to 10
M. Quantitative metal ion doping enables modulation of the device sensitivity and a quasi-quantitative detection of •OH generated in aqueous solution or from living cells. Owing to its high sensitivity, selectivity, real-time label-free response, capability for quasi-quantitative detection and user-friendly portable feature, it is valuable in biological research, human health, environmental monitoring, etc.
The prognostic values of tumor-infiltrating lymphocytes (TILs) and TILs subsets in breast cancer (BC) are uncertain.
A systematic literature search (MEDLINE, Web of Science, EMBASE, and the Cochrane ...Library to August 2014) was conducted for studies which met the eligibility criteria. The primary clinical outcome was defined as disease-free survival (DFS), overall survival (OS), and BC-specific survival (BCSS). Random or fixed-effects model was adopted to estimate the summary hazard ratio (HR).
Twenty-five published studies comprising 22,964 patients were reviewed. Pooled analysis indicated that TILs were not prognostic markers for DFS and OS in overall population, but related to improved DFS (HR, 0.82; 95% CI, 0.76-0.88) and OS (HR, 0.79; 95% CI, 0.71-0.87) in triple negative breast cancer (TNBC) patients. For TILs subsets, CD8+ lymphocytes were associated with improved DFS (HR, 0.69; 95% CI, 0.56-0.84) and BCSS (HR, 0.78; 95% CI, 0.71-0.86) in overall population, while FOXP3+ lymphocytes were associated with reduced DFS (HR, 1.47; 95% CI, 1.01-2.05) and OS (HR, 1.50; 95% CI, 1.15-1.97). In estrogen receptor (ER) negative patients, CD8+ lymphocytes was also related to better BCSS. In addition, the high density of CD20+, CD3+ or low level of PD-1+ or γδ T lymphocytes indicated increased OS in limited studies.
TILs and TILs subsets are promising prognostic biomarkers in breast cancer, especially in TNBC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Global warming, extreme climate events, earthquakes and their accompanying socioeconomic disasters pose significant risks to humanity. Yet due to the nonlinear feedbacks, multiple interactions and ...complex structures of the Earth system, the understanding and, in particular, the prediction of such disruptive events represent formidable challenges to both scientific and policy communities. During the past years, the emergence and evolution of Earth system science has attracted much attention and produced new concepts and frameworks. Especially, novel statistical physics and complex networks-based techniques have been developed and implemented to substantially advance our knowledge of the Earth system, including climate extreme events, earthquakes and geological relief features, leading to substantially improved predictive performances. We present here a comprehensive review on the recent scientific progress in the development and application of how combined statistical physics and complex systems science approaches such as critical phenomena, network theory, percolation, tipping points analysis, and entropy can be applied to complex Earth systems. Notably, these integrating tools and approaches provide new insights and perspectives for understanding the dynamics of the Earth systems. The overall aim of this review is to offer readers the knowledge on how statistical physics concepts and theories can be useful in the field of Earth system science.
Single‐cell RNA sequencing (scRNA‐seq) is a novel technology that allows transcriptomic analyses of individual cells. During the past decade, scRNA‐seq sensitivity, accuracy, and efficiency have ...improved due to innovations including more sensitive, automated, and cost‐effective single‐cell isolation methods with higher throughput as well as ongoing technological development of scRNA‐seq protocols. Among the variety of current approaches with distinct features, researchers can choose the most suitable method to carry out their research. By profiling single cells in a complex population mix, scRNA‐seq presents great advantages over traditional sequencing methods in dissecting heterogeneity in cell populations hidden in bulk analysis and exploring rare cell types associated with tumorigenesis and metastasis. scRNA‐seq studies in recent years in the field of breast cancer research have clustered breast cancer cell populations with different molecular subtypes to identify distinct populations that may correlate with poor prognosis and drug resistance. The technology has also been used to explain tumor microenvironment heterogeneity by identifying distinct immune cell subsets that may be associated with immunosurveillance and are potential immunotherapy targets. Moreover, scRNA‐seq has diverse applications in breast cancer research besides exploring heterogeneity, including the analysis of cell‐cell communications, regulatory single‐cell states, immune cell distributions, and more. scRNA‐seq is also a promising tool that can facilitate individualized therapy due to its ability to define cell subsets with potential treatment targets. Although scRNA‐seq studies of therapeutic selection in breast cancer are currently limited, the application of this technology in this field is prospective. Joint efforts and original ideas are needed to better implement scRNA‐seq technologies in breast cancer research to pave the way for individualized treatment management. This review provides a brief introduction on the currently available scRNA‐seq approaches along with their corresponding strengths and weaknesses and may act as a reference for the selection of suitable methods for research. We also discuss the current applications of scRNA‐seq in breast cancer research for tumor heterogeneity analysis, individualized therapy, and the other research directions mentioned above by reviewing corresponding published studies. Finally, we discuss the limitations of current scRNA‐seq technologies and technical problems that remain to be overcome.
We investigate the quantum phase transition of the anisotropic quantum Rabi model, in which the rotating and counterrotating terms are allowed to have different coupling strengths. The model ...interpolates between two known limits with distinct universal properties. Through a combination of analytic and numerical approaches, we extract the phase diagram, scaling functions, and critical exponents, which determine the universality class at finite anisotropy (identical to the isotropic limit). We also reveal other interesting features, including a superradiance-induced freezing of the effective mass and discontinuous scaling functions in the Jaynes-Cummings limit. Our findings are extended to the few-body quantum phase transitions with N>1 spins, where we expose the same effective parameters, scaling properties, and phase diagram. Thus, a stronger form of universality is established, valid from N=1 up to the thermodynamic limit.
We carried out a systematic review and meta-analysis to evaluate the predictive roles of tumor infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) in breast cancer.
A PubMed ...and Web of Science literature search was designed. Random or fixed effect models were adopted to estimate the summary odds ratio (OR). Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. Publication bias was evaluated using a funnel plot, Egger's test and Begg's test. We included studies where the predictive significance of TILs, and/or TILs subset on the pathologic complete response (pCR) were determined in NAC of breast cancer.
A total of 13 published studies (including 3251 patients) were eligible. In pooled analysis, the detection of higher TILs numbers in pre-treatment biopsy was correlated with better pCR to NAC (OR = 3.93, 95% CI, 3.26-4.73). Moreover, TILs predicted higher pCR rates in triple negative (OR = 2.49, 95% CI: 1.61-3.83), HER2 positive (OR = 5.05, 95% CI: 2.86-8.92) breast cancer, but not in estrogen receptor (ER) positive (OR = 6.21, 95%CI: 0.86-45.15) patients. In multivariate analysis, TILs were still an independent marker for high pCR rate (OR = 1.41, 95% CI: 1.19-1.66). For TILs subset, higher levels of CD8+ and FOXP3+ T-lymphocytes in pre-treatment biopsy respectively predicted better pathological response to NAC (OR = 6.44, 95% CI: 2.52-16.46; OR = 2.94, 95% CI: 1.05-8.26). Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80) and multivariate (OR = 0.36, 95% CI: 0.13-0.95) analysis.
Higher TILs levels in pre-treatment biopsy indicated higher pCR rates for NAC. TILs subset played different roles in predicting response to NAC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolic syndrome is a type of multifactorial metabolic disease with the presence of at least three factors: obesity, diabetes mellitus, low high-density lipoprotein, hypertriglyceridemia, and ...hypertension. Recent studies have shown that metabolic syndrome and its related components exert a significant impact on the initiation, progression, treatment response, and prognosis of breast cancer. Metabolic abnormalities not only increase the disease risk and aggravate tumor progression but also lead to unfavorable treatment responses and more treatment side effects. Moreover, biochemical reactions caused by the imbalance of these metabolic components affect both the host general state and organ-specific tumor microenvironment, resulting in increased rates of recurrence and mortality. Therefore, this review discusses the recent advances in the association of metabolic syndrome and breast cancer, providing potential novel therapeutic targets and intervention strategies to improve breast cancer outcome.
Air pollution fluctuations have been found to strongly depend on the weather dynamics. Here we identify the significant atmospheric processes that affect the local daily variability of air pollution. ...We develop a multilayered network analysis to detect the interlinks between the 500‐hPa geopotential height and surface air pollution in both China and the United States. We find that Rossby waves significantly affect air pollution fluctuations through the development of cyclone and anticyclone systems and further affect the local stability of the air and the winds. Some of these systems are remote (∼3,000 km) and lead to air pollution 1–2 days later. Thus, the impact of Rossby waves on human life is greater than previously believed. The rapid warming of the Arctic could slow down Rossby waves, thus increasing human health risks. Our method can help to determine the risk assessment of such extreme events and can improve potential predictability.
Plain Language Summary
Outdoor air pollution plays an important role in a wide range of environmental and health problems. The impact of weather dynamics (at different pressure levels) on the daily fluctuations of air pollution is still not clear. Here we develop a novel multilayer and multivariable network method to delineate the influence of the upper air dynamics on the temporal variability of surface air pollution. We show that the underlying mechanism of our observed relation between weather and air pollution is the dynamics of planetary Rossby waves that not only cause extreme weather events but also lead to strong fluctuations in air pollution. The developed method is applied on data from China and the United States and can help to improve the prediction of extreme pollution events.
Key Points
Surface pollution variations from China and the United States associated with atmospheric upper air conditions are studied by a network approach
The upper air critical regimes are found to significantly influence the surface air pollution
Rossby waves significantly affect air pollution fluctuations through low‐ and high‐pressure systems
The piezoresistive pressure sensor, a kind of widely investigated artificial device to transfer force stimuli to electrical signals, generally consists of one or more kinds of conducting materials. ...Here, a highly sensitive pressure sensor based on the semiconductor/conductor interface piezoresistive effect is successfully demonstrated by using organic transistor geometry. Because of the efficient combination of the piezoresistive effect and field‐effect modulation in a single sensor, this pressure sensor shows excellent performance, such as high sensitivity (514 kPa−1), low limit of detection, short response and recovery time, and robust stability. More importantly, the unique gate modulation effect in the transistor endows the sensor with an unparalleled ability—tunable sensitivity via bias conditions in a single sensor, which is of great significance for applications in complex pressure environments. The novel working principle and high performance represent significant progress in the field of pressure sensors.
A highly sensitive pressure sensor based on the semiconductor/conductor interface piezoresistive effect in organic field‐effect transistors is demonstrated. This sensor simultaneously displays high and tunable sensitivity due to combining the advantages of the piezoresistive effect and the field‐effect modulation. In addition, the quick response speed and robust working performance show its potential in subtle and complex pressure environments.
Stat6 is known to drive macrophage M2 polarization. However, how macrophage polarization is fine-tuned by Stat6 is poorly understood. Here, we find that Lys383 of Stat6 is acetylated by the ...acetyltransferase CREB-binding protein (CBP) during macrophage activation to suppress macrophage M2 polarization. Mechanistically, Trim24, a CBP-associated E3 ligase, promotes Stat6 acetylation by catalyzing CBP ubiquitination at Lys119 to facilitate the recruitment of CBP to Stat6. Loss of Trim24 inhibits Stat6 acetylation and thus promotes M2 polarization in both mouse and human macrophages, potentially compromising antitumor immune responses. By contrast, Stat6 mediates the suppression of TRIM24 expression in M2 macrophages to contribute to the induction of an immunosuppressive tumor niche. Taken together, our findings establish Stat6 acetylation as an essential negative regulatory mechanism that curtails macrophage M2 polarization.
PDF
