Diabetic nephropathy (DN) is one of the most common complications in diabetes mellitus and the leading cause of end-stage renal disease. TGF-β is a pleiotropic cytokine and has been recognized as a ...key mediator of DN. However, anti-TGF-β treatment for DN remains controversial due to the diverse role of TGF-β1 in DN. Thus, understanding the regulatory role and mechanisms of TGF-β in the pathogenesis of DN is the initial step towards the development of anti-TGF-β treatment for DN. In this review, we first discuss the diverse roles and signaling mechanisms of TGF-β in DN by focusing on the latent versus active TGF-β1, the TGF-β receptors, and the downstream individual Smad signaling molecules including Smad2, Smad3, Smad4, and Smad7. Then, we dissect the regulatory mechanisms of TGF-β/Smad signaling in the development of DN by emphasizing Smad-dependent non-coding RNAs including microRNAs and long-non-coding RNAs. Finally, the potential therapeutic strategies for DN by targeting TGF-β signaling with various therapeutic approaches are discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Boron‐doped fused heterocycles have shown great potential in the field of functional materials. This study reports on the synthesis of a new class of bis‐diazidoboranes and the discovery of their ...cycloaddition reaction with isonitriles. Triply fused boron‐doped heterocyclic compounds were constructed in a one‐pot process through a domino cycloaddition, providing an effective route for constructing complex boron‐doped heterocyclic systems.
The room temperature domino cyclization reaction of bis‐diazidoboranes with isonitriles was reported for the first time. This one‐step reaction leads to complex boron‐doped fused heterocycles and provides a new strategy for the construction of boron‐doped heterocyclic systems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on the infiltration ...of T cells capable of recognizing and killing tumor cells. ICIs are not effective in "cold tumors", which are characterized by the lack of T-cell infiltration. To realize the full potential of immunotherapy and solve this obstacle, it is essential to understand the drivers of T-cell infiltration into tumors. We present a critical review of our understanding of the mechanisms underlying "cold tumors", including impaired T-cell priming and deficient T-cell homing to tumor beds. "Hot tumors" with significant T-cell infiltration are associated with better ICI efficacy. In this review, we summarize multiple strategies that promote the transformation of "cold tumors" into "hot tumors" and discuss the mechanisms by which these strategies lead to increased T-cell infiltration. Finally, we discuss the application of nanomaterials to tumor immunotherapy and provide an outlook on the future of this emerging field. The combination of nanomedicines and immunotherapy enhances cross-presentation of tumor antigens and promotes T-cell priming and infiltration. A deeper understanding of these mechanisms opens new possibilities for the development of multiple T cell-based combination therapies to improve ICI effectiveness.
Although cell-cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, nonapoptotic form of cell ...death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as a key factor in modulating SLC7A11 stability. OTUB1 directly interacted with and stabilized SLC7A11; conversely, OTUB1 knockdown diminished SLC7A11 levels in cancer cells. OTUB1 was overexpressed in human cancers, and inactivation of OTUB1 destabilized SLC7A11 and led to growth suppression of tumor xenografts in mice, which was associated with reduced activation of ferroptosis. Notably, overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. Together, these results show that OTUB1 plays an essential role in controlling the stability of SLC7A11 and the CD44-mediated effects on ferroptosis in human cancers. SIGNIFICANCE: This study identifies OTUB1 as a key regulator of ferroptosis and implicates it as a potential target in cancer therapy.
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•The mechanisms of microwave absorption were analyzed in detail.•The preparation methods of carbon/magnetic metal composites were summarized.•Composites with different components, ...morphologies and structures were reviewed.•Challenges and future prospects for carbon/magnetic metal composites were proposed.
At present, developing high-efficiency microwave absorption materials with properties including light-weight, thin thickness, strong absorbing intensity and broad bandwidth is an urgent demand to solve the electromagnetic pollution issues. An ideal microwave absorber should have excellent dielectric and magnetic loss capabilities, thereby inducing attenuation and absorption of incident electromagnetic radiation. Recently, various carbon/magnetic metal composites have been developed and expected to become promising candidates for high-performance microwave absorbers. In this review, we introduce the mechanisms of microwave absorption and summarize the recent advances in carbon/magnetic metal composites. Preparation methods and microwave absorption properties of carbon/magnetic metal composites with different components, morphologies and microstructures are discussed in detail. Finally, the challenges and future prospects of carbon/magnetic metal absorbing materials are also proposed, which will be useful to develop high-performance microwave absorption materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Functionalization of hydrogen‐bonded organic frameworks (HOFs) for specific applications has been a long‐lasting challenge in HOF materials. Here, an efficient way to integrate functional species in ...the HOF structure through constructing an anionic framework is presented. The obtained HOFs, taking PFC‐33 (PFC = porous materials from FJIRSM,CAS) as an example, integrate a porphyrin photosensitizer as a porous backbone and a commercial biocide as counterions in the structure. The permanent channels and the electrostatic interaction between the framework and the counterions provide PFC‐33 ion‐responsive biocide‐release behavior in various physiological environments, thus exhibiting synergistic photodynamic and chemical antimicrobial efficiency. The unbonded carboxyl groups residing on the HOF surface further allow for manipulating the interfacial interaction between the PFC‐33 and the polymer matrix for membrane fabrication. Therefore, a polyHOF membrane with high stability, desired flexibility, and good permeability is obtained, which demonstrates noticeable bacterial inhibition toward Escherichia coli. This study may shed light on the functionalization of HOF materials for broad application potentials.
The functionalization of hydrogen‐bonded organic frameworks (HOFs) can be achieved in a porphyrin‐based anionic HOF structure, endowing the material with synergistic photodynamic and chemical antimicrobial efficacy. By further taking advantage of the unbonded carboxyl groups on the HOF particle surface, a freestanding flexible membrane that shows high permeability, good stability, and excellent antibacterial activity is successfully fabricated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the developing brain, immature synapses contain calcium-permeable AMPA glutamate receptors (AMPARs) that are subsequently replaced with GluA2-containing calcium-impermeable AMPARs as synapses ...stabilize and mature. Here, we show that this essential switch in AMPARs and neuronal synapse maturation is regulated by astrocytes. Using biochemical fractionation of astrocyte-secreted proteins and mass spectrometry, we identified that astrocyte-secreted chordin-like 1 (Chrdl1) is necessary and sufficient to induce mature GluA2-containing synapses to form. This function of Chrdl1 is independent of its role as an antagonist of bone morphogenetic proteins (BMPs). Chrdl1 expression is restricted to cortical astrocytes in vivo, peaking at the time of the AMPAR switch. Chrdl1 knockout (KO) mice display reduced synaptic GluA2 AMPARs, altered kinetics of synaptic events, and enhanced remodeling in an in vivo plasticity assay. Studies have shown that humans with mutations in Chrdl1 display enhanced learning. Thus astrocytes, via the release of Chrdl1, promote GluA2-dependent synapse maturation and thereby limit synaptic plasticity.
•Astrocytes regulate synapse maturation by controlling AMPA receptor subtype•Astrocyte-secreted Chrdl1 increases synaptic levels of GluA2 AMPA receptors•Chrdl1 KO mice have immature synapses•Chrdl1 KO mice show enhanced plasticity in vivo, which is maintained into adulthood
Blanco-Suarez et al. identify that synapse maturation is not intrinsic to neurons but is regulated by neighboring astrocytes. They demonstrate that astrocyte-secreted Chrdl1 increases GluA2 AMPA receptor levels at synapses, inducing synapse maturation and inhibiting plasticity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study uses satellite data to detect agricultural straw burning and estimates its impact on air pollution and health in China. We find that straw burning increases particulate matter pollution ...and causes people to die from cardiorespiratory diseases. We estimate that a 10 μg/m3 increase in PM2.5 increases mortality by 3.25%. Middle-aged and old people in rural areas are particularly sensitive to straw burning pollution. Exploratory analysis of China’s programs to subsidize straw recycling suggests that extending these programs to all the straw burning regions would bring about a health benefit that is an order of magnitude larger than the cost.
•Satellite data are used to detect straw fires.•Straw burning significantly increases air pollution and cardiorespiratory mortality.•A 10 μg/m3 increase in PM2.5 increases monthly mortality by 3.25%.•Middle-aged and old people are particularly vulnerable to straw burning pollution.•Subsidizing straw recycling can bring about significant health benefits.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nitrogen fixation is essential for the maintenance of life and development of society, however, the large bond dissociation energy and nonpolarity of the triple bond constitute a considerable ...challenge. The transition metals, by virtue of their combination of empty and occupied d orbitals, are prevalent in the nitrogen fixation studies and are continuing to receive a significant focus. The main group metals have always been considered incapable in dinitrogen activation owing to the absence of energetically and symmetrically accessible orbitals. The past decades have witnessed significant breakthroughs in the dinitrogen activation with the main group elements and compounds
via
either matrix isolation, theoretical calculations or synthetic chemistry. The successful reactions of the low-valent species of the main group elements with inert dinitrogen have been reported
via
the π back-donation from either the d orbitals (Ca, Sr, Ba) or p orbitals (Be, B, C...). Herein, the significant achievements have been briefly summarized, along with predicting the future developments.
In this tutorial, we introduced the fundamental aspects of nitrogen fixation, summarized the recent progresses with main group elements and tried to make clear the clue for further developments.
Fully supervised semantic segmentation has performed well in many computer vision tasks. However, it is time-consuming because training a model requires a large number of pixel-level annotated ...samples. Few-shot segmentation has recently become a popular approach to addressing this problem, as it requires only a handful of annotated samples to generalize to new categories. However, the full utilization of limited samples remains an open problem. Thus, in this article, a mutually supervised few-shot segmentation network is proposed. First, the feature maps from intermediate convolution layers are fused to enrich the capacity of feature representation. Second, the support image and query image are combined into a bipartite graph, and the graph attention network is adopted to avoid losing spatial information and increase the number of pixels in the support image to guide the query image segmentation. Third, the attention map of the query image is used as prior information to enhance the support image segmentation, which forms a mutually supervised regime. Finally, the attention maps of the intermediate layers are fused and sent into the graph reasoning layer to infer the pixel categories. Experiments are conducted on the PASCAL VOC-<inline-formula> <tex-math notation="LaTeX">5^{i} </tex-math></inline-formula> dataset and FSS-1000 dataset, and the results demonstrate the effectiveness and superior performance of our method compared with other baseline methods.
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