Sex differences in innate and adaptive immune responses are known, and women generally mount a stronger immune response than men. Cancer immunotherapy, represented by immune checkpoint inhibitors ...(ICIs), has revolutionized the treatment of cancer, and sex differences in cancer immunotherapy are just starting to be revealed. Here, we summarize recent research progress concerning sex differences in cancer immunotherapy efficacy. On their own, ICIs tend to be more effective in male cancer patients compared with female patients, while ICIs combined with chemotherapy tend to be more effective in female patients than male patients. Male tumors are usually more antigenic than female tumors, and this is reflected by their increased number of tumor mutations and cancer germline antigens. The biomarker tumor mutational burden (TMB), which reflects tumor antigenicity, is more effective at predicting immunotherapy response for female lung cancer patients than for male patients. In this review, we propose different therapeutic strategies for the different sexes: For male cancer patients, the immune environment should be enhanced, whereas for female cancer patients, tumor antigenicity should be enhanced.
The aryl‐to‐vinyl nickel 1,4‐migration (1,4‐Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated ...brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4‐Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.
The 1,4‐nickel migration process from aryl to alkenyl groups is now reported for the first time. The alkenyl nickel intermediates generated by this highly stereoselective migration process can be coupled with brominated alkanes to form multisubstituted olefins. The current method provides a new and efficient approach for the synthesis of Z/E olefins with high stereoselectivity.
Immunotherapy, represented by immune checkpoint inhibitors (ICI), is transforming the treatment of cancer. However, only a small percentage of patients show response to ICI, and there is an unmet ...need for biomarkers that will identify patients who are more likely to respond to immunotherapy. The fundamental basis for ICI response is the immunogenicity of a tumor, which is primarily determined by tumor antigenicity and antigen presentation efficiency. Here, we propose a method to measure tumor immunogenicity score (TIGS), which combines tumor mutational burden (TMB) and an expression signature of the antigen processing and presenting machinery (APM). In both correlation with pan-cancer ICI objective response rates (ORR) and ICI clinical response prediction for individual patients, TIGS consistently showed improved performance compared to TMB and other known prediction biomarkers for ICI response. This study suggests that TIGS is an effective tumor-inherent biomarker for ICI-response prediction.
Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have ...been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.
A series of lanthanide metal‐organic frameworks (Ln‐MOFs) are synthesized through solvothermal conditions with 1,3‐bis(4‐carboxyphenyl)imidazolium (H2L). Owing to the lanthanide contraction effect, ...two different types of Ln‐MOFs, namely, {Ln(L)2(OH)·3H2O}n (Ln:Pr, Nd, Sm) and {Ln(L)2(COO)(H2O)2·H2O}n (Ln: Eu, Gd, Tb, Dy, Tm, Yb, Y), and their corresponding codoped Ln‐MOFs EuxTb1‐xL are obtained. With careful adjustment of the relative concentration of the lanthanide ions and the excitation wavelength, the color of the luminescence can be systematically modulated and white light emission can be further successfully achieved. Furthermore, by virtue of the temperature‐dependent luminescent behavior, Eu0.2Tb0.8L allows for the design of a thermometer with an excellent linear response to temperature over a wide range, from 40 to 300 K. This work highlights the practical applications of Ln‐MOFs for tailoring fluorescent color and even obtaining practical white light emission, and especially for sensing temperature as luminescent thermometers in a single framework by controlling in different ways.
Codoped Ln‐metal‐organic frameworks EuxTb1‐xL are synthesized based on the isostructural Ln‐metal‐organic frameworks using lanthanide ion emitters. With careful adjustment of the relative concentration of the lanthanide ions and the excitation wavelength, the emission trajectory can be modulated, allowing white emission. Furthermore, Eu0.2Tb0.8L allows for the design of a thermometer operating over a wide range, from 40 to 300 K.
The synthesis of all-carbon tetrasubstituted olefins under mild reaction conditions is challenging because of the inevitable issues including significant steric hindrance and the uncontrolled Z/E ...stereoselectivity. In this paper, we report the synthesis of all-carbon tetrasubstituted alkenes from readily available carboxylic acids and alkenyl triflates with the synergistic catalysis of cyclo-octa-1,5-diene(tetramethyl-1,4-benzoquinone)nickel and visible light under an air atmosphere, thus avoiding the need for a glovebox or a Schlenk line. A wide range of aromatic carboxylic acids and cyclic and acyclic alkenyl triflates undergo the C-C coupling process smoothly, forming structurally diverse alkenes stereospecifically in moderate to good yields. The practicality of the method is further illustrated by the late-stage modification of complex molecules, the one pot synthesis and gram-scale applications. This is an important step towards the valuable utilization of carboxylic acids, and it also simplifies the experimental operation of metallophotoredox catalysis with moisture sensitive nickel(0) catalysis.
Foodborne protein hydrolysates exhibit biological activity that may be therapeutic in a number of human disease settings. Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a ...number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl‐2. HP treatment led to increased Akt and GSK‐3β phosphorylation, with subsequent downregulation of β‐catenin, suggesting β‐catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment.
Anti‐cancer property of new hemp protein hydrolysates on human liver cancers
•Comprehensive information of classification and physiological activity of biogenic amines.•Updated information on sample pretreatment and analytical methods of biogenic amines.•Separation ...conditions, analytical conditions and validation information are compared.•Abundant figures and tables are offered.
Biogenic amines (BAs), mainly produced by amino acid decarboxylation, are widespread in foods and human organisms. Appropriate intake of BAs is beneficial to the human body, while excessive consumption may cause discomfort. Meanwhile, BAs are a kind of chemical marker for evaluating meat freshness. For these reasons, simple, rapid and efficient methods have been developed for the determination of BAs in food and biological products. This review introduces the provenance, classification and physiological activity of eight essential BAs and summarizes the dominant pretreatment and analysis methods since 2010. Pretreatment technologies mainly include the “dilute and shoot” method, ultrasonic assisted extraction, solid-phase extraction, matrix solid-phase dispersion, dispersive liquid-liquid microextraction, etc. Determination methods include liquid chromatography coupled to ultraviolet or fluorescence detectors, liquid chromatography tandem mass spectrometry, capillary electrophoresis, biosensors and so on.
In response to the stringent emission regulations, artificial neural network (ANN) coupled with genetic algorithm (GA) is employed to optimize a novel internal combustion engine strategy named direct ...dual fuel stratification (DDFS). An enhanced ANN model is introduced to improve the accuracy and stability of predictions. Compared to the conventional computational fluid dynamics (CFD)-GA optimization method, the ANN-GA method can identify a better solution to achieve higher fuel efficiency and lower nitrogen oxide (NOx) emissions with the lower computational time. This is attributed to the lower cost of ANN calculation, which allows ANN-GA to introduce larger population to seek optimal solutions. Through combining the required new training data with the previous ones, the original ANN model can be updated to adapt to a wider parameter range. Thus, ANN-GA can readily deal with the optimization problems with variable parameters and objectives. When more re-optimizations are required, ANN-GA can save the computational time over 75% than CFD-GA owing to the data-driven nature of ANN-GA by fully utilizing the available data. Overall, the ANN-GA method shows the superiority in accuracy, efficiency, expansibility, and flexibility for DDFS strategy optimization. It is promising to integrate ANN with optimization algorithm for further improvements of engine performance.
•Machine learning with genetic algorithm is used to enhance engine optimization.•An enhanced ANN model is proposed to improve accuracy and stability of prediction.•ANN-GA can adapt to engine optimization with variable parameters and objectives.•Higher engine efficiency is achieved by ANN-GA method without other penalties.•ANN-GA method shows merit in accuracy, efficiency, expansibility, and flexibility.