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.
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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.
The
D
(
∗
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Ξ
cc
(
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system and
Ξ
¯
cc
(
∗
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Ξ
cc
(
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system can be related to the
D
(
∗
)
D
¯
(
∗
)
system via heavy anti-quark di-quark symmetry (HADS). In this work, we employ a contact-range ...effective field theory to systematically investigate the likely existence of molecules in these systems in terms of the hypothesis that X(3872) is a
1
+
+
D
D
¯
∗
bound state in the isospin symmetry limit, with some of the unknown low energy constants estimated using the light-meson saturation approximation. In the meson–meson system, a
J
PC
=
2
+
+
D
¯
∗
D
∗
molecule commonly referred to as
X
(4013) is reproduced, which is the heavy quark spin partner of
X
(3872). In the meson-baryon system, we predict two triply charmed pentaquark molecules,
J
P
=
1
/
2
-
D
∗
Ξ
cc
and
J
P
=
5
/
2
-
D
∗
Ξ
cc
∗
. In the baryon-baryon system, there exist seven di-baryon molecules,
J
PC
=
0
-
+
Ξ
¯
cc
Ξ
cc
,
J
PC
=
1
-
-
Ξ
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cc
Ξ
cc
,
J
PC
=
1
-
+
Ξ
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cc
Ξ
cc
∗
,
J
PC
=
1
-
-
Ξ
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cc
Ξ
cc
∗
,
J
PC
=
2
-
+
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cc
Ξ
cc
∗
,
J
PC
=
2
-
+
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cc
∗
Ξ
cc
∗
, and
J
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=
3
-
-
Ξ
¯
cc
∗
Ξ
cc
∗
. Among them, the
J
PC
=
0
-
+
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cc
Ξ
cc
molecule may contribute to the
X
(7200) state recently observed by the LHCb Collaboration, which implies that
X
(7200) can be related to
X
(3872) via HADS. As a byproduct, with the heavy quark flavor symmetry we also study likely existence of molecular states in the
B
(
∗
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B
¯
(
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,
B
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(
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bb
(
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, and
Ξ
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bb
(
∗
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Ξ
bb
(
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systems.
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.
A recent analysis by the LHCb Collaboration suggests the existence of three narrow pentaquarklike states-the P_{c}(4312), P_{c}(4440), and P_{c}(4457)-instead of just one in the previous analysis the ...P_{c}(4450). The closeness of the P_{c}(4312) to the Dover ¯Σ_{c} threshold and the P_{c}(4440) and P_{c}(4457) to the Dover ¯^{*}Σ_{c} threshold suggests a molecular interpretation of these resonances. We show that these three pentaquarklike resonances can be naturally accommodated in a contact-range effective field theory description that incorporates heavy-quark spin symmetry. This description leads to the prediction of all the seven possible S-wave heavy antimeson-baryon molecules that is, there should be four additional molecular pentaquarks in addition to the P_{c}(4312), P_{c}(4440), and P_{c}(4457), providing the first example of a heavy-quark spin symmetry molecular multiplet that is complete. If this is confirmed, it will not only give us an impressive example of the application of heavy-quark symmetries and effective field theories in hadron physics, it will also uncover a clear and powerful ordering principle for the molecular spectrum, reminiscent of the SU(3)-flavor multiplets to which the light hadron spectrum conforms.
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