Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer ...research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.
Unprecedented dual aggregation‐induced emission (AIE) behavior based on a steric‐hindrance photochromic system is presented, with incorporation one or two bulky aryl groups, resulting in different ...flexibleness. The dual AIE behavior of open and closed isomers can be explained by restriction of intramolecular rotation (RIR), restriction of intramolecular vibration (RIV), and intermolecular stacking. The large bulky benzothiophene causes restricted rotation, enhancing the emission of open form in solution and weak π–π molecular packing, thereby efficiently enhancing the luminescence performance in the solid state. With incorporation of two large bulky benzothiophene groups, BBTE possesses the most outstanding AIE activity, undergoing highly efficient and reversible off‐to‐on fluorescence in film upon alternating UV and visible light irradiation along with excellent fatigue resistance. The off‐to‐on fluorescent photoswitch is successfully established in super resolution imaging.
Dual AIE behavior: The steric‐hindrance photochromic system efficiently regulates the intramolecular rotational/vibrational magnitude and intermolecular stacking to tune aggregation‐induced emission (AIE) activity. The off‐to‐on fluorescent photoswitch is successfully established in super resolution imaging.
Summary
Seed development largely depends on the long‐distance transport of sucrose from photosynthetically active source leaves to seed sinks. This source‐to‐sink carbon allocation occurs in the ...phloem and requires the loading of sucrose into the leaf phloem and, at the sink end, its import into the growing embryo. Both tasks are achieved through the function of SUT sucrose transporters. In this study, we used vegetable peas (Pisum sativum L.), harvested for human consumption as immature seeds, as our model crop and simultaneously overexpressed the endogenous SUT1 transporter in the leaf phloem and in cotyledon epidermal cells where import into the embryo occurs. Using this ‘Push‐and‐Pull’ approach, the transgenic SUT1 plants displayed increased sucrose phloem loading and carbon movement from source to sink causing higher sucrose levels in developing pea seeds. The enhanced sucrose partitioning further led to improved photosynthesis rates, increased leaf nitrogen assimilation, and enhanced source‐to‐sink transport of amino acids. Embryo loading with amino acids was also increased in SUT1‐overexpressors resulting in higher protein levels in immature seeds. Further, transgenic plants grown until desiccation produced more seed protein and starch, as well as higher seed yields than the wild‐type plants. Together, the results demonstrate that the SUT1‐overexpressing plants with enhanced sucrose allocation to sinks adjust leaf carbon and nitrogen metabolism, and amino acid partitioning in order to accommodate the increased assimilate demand of growing seeds. We further provide evidence that the combined Push‐and‐Pull approach for enhancing carbon transport is a successful strategy for improving seed yields and nutritional quality in legumes.
Significance Statement
We demonstrate that carbon allocation from source to sink and seed carbon pools can be improved in legumes through synergistically enhancing leaf export and seed uptake of sucrose. In addition, changes in source‐to‐sink carbon transport affect seed protein levels though improved leaf metabolism and amino acid partitioning to, and uptake into, the embryo.
Positron emission tomography (PET) imaging is an effective tool used in determining disease stage and lesion malignancy; however, radiation exposure to patients and technicians during PET scans ...continues to draw concern. One way to minimize radiation exposure is to reduce the dose of radioactive tracer administered in order to obtain the scan. Yet, low-dose images are inherently noisy and have poor image quality making them difficult to read. This paper proposes the use of a deep learning model that takes specific image features into account in the loss function to denoise low-dose PET image slices and estimate their full-dose image quality equivalent. Testing on low-dose image slices indicates a significant improvement in image quality that is comparable to the ground truth full–dose image slices. Additionally, this approach can lower the cost of conducting a PET scan since less radioactive material is required per scan, which may promote the usage of PET scans for medical diagnosis.
Flexible fiber‐shaped supercapacitors have shown great potential in portable and wearable electronics. However, small specific capacitance and low operating voltage limit the practical application of ...fiber‐shaped supercapacitors in high energy density devices. Herein, direct growth of ultrathin MnO2 nanosheet arrays on conductive carbon fibers with robust adhesion is exhibited, which exhibit a high specific capacitance of 634.5 F g−1 at a current density of 2.5 A g−1 and possess superior cycle stability. When MnO2 nanosheet arrays on carbon fibers and graphene on carbon fibers are used as a positive electrode and a negative electrode, respectively, in an all‐solid‐state asymmetric supercapacitor (ASC), the ASC displays a high specific capacitance of 87.1 F g−1 and an exceptional energy density of 27.2 Wh kg−1. In addition, its capacitance retention reaches 95.2% over 3000 cycles, representing the excellent cyclic ability. The flexibility and mechanical stability of these ASCs are highlighted by the negligible degradation of their electrochemical performance even under severely bending states. Impressively, as‐prepared fiber‐shaped ASCs could successfully power a photodetector based on CdS nanowires without applying any external bias voltage. The excellent performance of all‐solid‐state ASCs opens up new opportunity for development of wearable and self‐powered nanodevices in near future.
Wearable, fiber‐shaped, and all‐solid‐state asymmetric supercapacitors (ASCs) are successfully constructed with a maximum operating voltage of 1.5 V using ultrathin MnO2 nanosheets and graphene on carbon fibers as positive and negative electrode, respectively. The fabricated fiber‐shaped ASCs display excellent bendability and mechanical stability, and possess enough energy to power a CdS nanowire photodetector without applying any external bias voltage.
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•A dual-functional ultrafiltration membrane containing quaternary ammonium and zwitterionic polymers was prepared.•The antifouling and antibacterial behavior of the membrane was ...studied.•The membrane showed the improved organic-/bio fouling resistance.•The membrane showed high-efficiency broad-spectrum antibacterial performance.
To overcome the organic-/bio- fouling of the membrane, a dual-functional ultrafiltration membrane containing quaternary ammonium and zwitterionic polymers via quaternization and surface radical polymerization was designed, and its antifouling and antibacterial behavior was studied. In this work, poly(vinylidene fluoride)/poly(methyl methacrylate-co-dimethylamino-2-ethyl methacrylate) (PVDF/P(MMA-co-DMAEMA)) blend membrane was quaternized by p-chloromethyl styrene (p-CMS), and the double bonds were introduced onto the membrane surface, which further participated in the polymerization of zwitterionic monomers on the membrane surface. The results indicated that the resultant membrane exhibited obviously improved hydrophilicity and weak positive charge (isoelectric point, 7.49). The membrane presented higher flux recovery ratio and lower protein adhesion compared with the pure PVDF membrane. Meanwhile, the membrane showed high-efficiency broad-spectrum antibacterial performance, that is, the bacteria killing efficiency of S. aureus and E. coli reached 98.2% and 97.0%, respectively. Moreover, the membrane effectively inhibited bacterial adhesion, which is important for the long-term antibacterial properties of membrane. This antifouling and antibacterial PVDF membrane may have potential in the long-term filtration process, especially when dealing with microbiologically contaminated water.
Proteins are responsible for the occurrence and treatment of many diseases, and therefore protein sequencing will revolutionize proteomics and clinical diagnostics. Biological nanopore approach has ...proved successful for single‐molecule DNA sequencing, which resolves the identities of 4 natural deoxyribonucleotides based on the current blockages and duration times of their translocations across the nanopore confinement. However, open challenges still remain for biological nanopores to sequentially identify each amino acid (AA) of single proteins due to the inherent complexity of 20 proteinogenic AAs in charges, volumes, hydrophobicity and structures. Herein, we focus on recent exciting advances in biological nanopores for single‐molecule protein sequencing (SMPS) from native protein unfolding, control of peptide translocation, AA identification to applications in disease detection.
Nanopore electrochemistry offers a bright prospect for single‐molecule protein sequencing by measuring specific interactions between amino acids based on their natural structure and chemistry continuity and diversity. This Minireview focusses on recent advances in biological nanopores from protein unfolding, peptide translocation, amino acid identification to diagnostic application.
Eucommia ulmoides Oliver (EUO), a traditional Chinese herb, contains a variety of bioactive chemicals, including lignans, iridoids, phenolics, steroids, terpenoids, flavonoids, etc. These bioactive ...chemicals possess the effective function in nourishing the liver and kidneys and regulating blood pressure. The composition of bioactive chemicals extracted from EUO vary in the different functional parts (leaves, seeds, bark, and staminate flower) and planting models. The bioactive parts of EUO are widely used as raw materials for medicine and food, powdery extracts, herbal formulations, and tinctures. These capabilities hold potential for future development and commercial exploitation of the bioactive products from EUO.
An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an ...oxidative 1,3‐dicarbonyl radical‐initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica‐gel‐promoted semipinacol rearrangement to form the 6‐oxabicyclo3.2.1octane skeleton and the Suzuki–Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.
The enantioselective total syntheses of fungal meroterpenoids, manginoids A and C, as well as guignardones A and C, are accomplished. This divergent and bioinspired synthetic strategy involves a Csp3−Csp2 Suzuki–Miyaura coupling of vinyl bromide, silica‐gel‐promoted semipinacol rearrangement, and oxidative 1,3‐dicarbonyl radical‐initiated cyclization.
Research Summary
I present evidence of a shift in the relative contributions of industry and corporate effects to heterogeneity in business performance in the United States. In a systematic analysis ...of sequential timeframes between 1978 and 2019, I find a persistent rise in the explanatory power of corporate effects, which has grown to surpass that of industry effects. Consistent with these trends, I also find that an increasing share of multi‐business firms is operating only high‐performing or only low‐performing businesses, which coincides with refocusing efforts that began in the 1980s. This temporal perspective provides an explanation for why prior studies estimating industry and corporate effects have reached different conclusions.
Managerial Summary
I present evidence that how much industry and corporate parentage each matter to business performance among diversified firms in the United States has changed over time in a systematic way. Specifically, my analyses show that while factors at the industry level may have mattered more than those at the corporate level from the late 1970s through most of the 1990s, this has since reversed and corporate parentage likely explained more of business profitability throughout the 2000s and 2010s than industry membership. These changes coincide with a trend that began in the 1980s toward greater focus and relatedness among the operations of diversified firms.
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