Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.
Tin diselenide (SnSe2) nanosheets as novel 2D layered materials have excellent optical properties with many promising application prospects, such as photoelectric detectors, nonlinear optics, ...infrared photoelectric devices, and ultrafast photonics. Among them, ultrafast photonics has attracted much attention due to its enormous advantages; for instance, extremely fast pulse, strong peak power, and narrow bandwidth. In this work, SnSe2 nanosheets are fabricated by using solvothermal treatment, and the characteristics of SnSe2 are systemically investigated. In addition, the solution of SnSe2 nanosheets is successfully prepared as a fiber‐based saturable absorber by utilizing the evanescent field effect, which can bear a high pump power. 31st‐order subpicosecond harmonic mode locking is generated in an Er‐doped fiber laser, corresponding to the maximum repetition rate of 257.3 MHz and pulse duration of 887 fs. The results show that SnSe2 can be used as an excellent nonlinear photonic device in many fields, such as frequency comb, lasers, photodetectors, etc.
Tin diselenide (SnSe2) nanosheets as novel 2D layered materials have excellent optical properties. SnSe2 nanosheets fabricated by using solvothermal treatment are successfully prepared as fiber‐based saturable absorbers by utilizing the evanescent field effect, which can bear a high pump power. 31st‐order subpicosecond harmonic mode‐locking is generated, corresponding to 257.3 MHz repetition rate.
Members of the transforming growth factor-β (TGF-β) family regulate cell fate decisions during early embryonic development and tissue homeostasis in the adult. Deregulation of TGF-β family signaling ...contributes to developmental anomalies, fibrotic disorders, tumorigenesis and immune diseases. TGF-β exerts a wide spectrum of cellular functions by activating canonical (SMAD-dependent) or non-canonical (SMAD-independent) pathways in a cell type-specific and context-dependent manner. Here, we focus on recent advances in the understanding of the mechanisms and functions of SMAD and non-SMAD pathways in physiology and pathology.
The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, prevents the toxins, blood cells, and pathogens from entering the spinal cord and maintains a ...tightly controlled chemical balance in the spinal environment, which is necessary for proper neural function. A BSCB disruption, however, plays an important role in primary and secondary injury processes related to spinal cord injury (SCI). After SCI, the structure of the BSCB is broken down, which leads directly to leakage of blood components. At the same time, the permeability of the BSCB is also increased. Repairing the disruption of the BSCB could alleviate the SCI pathology. We review the morphology and pathology of the BSCB and progression of therapeutic methods targeting BSCB in SCI.
Under an atmosphere of carbon monoxide (CO), a (phosphino)diazomethyl anion salt P‐CN2K(18‐C‐6)(THF) (1) (P=(CH2)(NDipp)2P; 18‐C‐6=18‐crown‐6; Dipp=2,6‐diisopropylphenyl) undergoes a facile N2/CO ...exchange reaction giving the (phosphino)ketenyl anion salt P‐CCOK(18‐C‐6) (2). Oxidation of 2 with elemental Se affords the (selenophosphoryl)ketenyl anion salt P(Se)‐CCOK(18‐C‐6) (3). These ketenyl anions feature a strongly bent geometry at the P‐bound carbon and this carbon atom is highly nucleophilic. The electronic structure of the ketenyl anion P‐CCO− of 2 is examined by theoretical studies. Reactivity investigations demonstrate 2 as a versatile synthon for derivatives of ketene, enolate, acrylate and acrylimidate moieties.
Under an atmosphere of carbon monoxide, a (phosphino)diazomethyl anion salt (1) undergoes a facile N2/CO exchange reaction giving a (phosphino)ketenyl anion salt (2). Reactivity investigations showed that the ketenyl anion can be a versatile synthon for derivatives of ketene, enolate, acrylate and acrylimidate moieties.
Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron‐mediated Fenton reactions. It has been reported that iron deficiency had been ...implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis. Our in vitro models show the changes in protein levels of ferroptosis marker and enhanced lipid peroxidation level during oxidative stress. Safranin O staining, hematoxylin‐eosin staining, and immunohistochemical were used to assess the IVDD after 8 weeks of surgical procedure in vivo. Treatment with ferrostatin‐1, deferoxamine, and RSL3 demonstrate the role of ferroptosis in tert‐butyl hydroperoxide (TBHP)‐treated annulus fibrosus cells (AFCs) and nucleus pulposus cells (NPCs). Ferritinophagy, nuclear receptor coactivator 4 (NCOA4)‐mediated ferritin selective autophagy, is originated during the process of ferroptosis in response to TBHP treatment. Knockdown and overexpression NCOA4 further prove TBHP may induce ferroptosis of AFCs and NPCs in an autophagy‐dependent way. These findings support a role for oxidative stress‐induced ferroptosis in the pathogenesis of IVDD.
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Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron‐mediated Fenton reactions. It has been reported that iron deficiency had been implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis.
Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing ...therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPβ, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPβ can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPβ may provide more precise therapeutic options in ovarian cancer.
Background and Aims
Hepatic macrophages can be activated by many factors such as gut‐derived bacterial components and factors released from damaged hepatocytes. Macrophage polarization toward a ...proinflammatory phenotype (M1) represents an important event in the disease progression of nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms remain incompletely understood. Exosomes have been identified as important mediators for cell–cell communication by transferring various biological components such as microRNAs (miRs), proteins, and lipids. The role of exosomes in crosstalk between hepatocytes and macrophages in disease progression of NAFLD is yet to be explored.
Approach and Results
In the present study, we reported that lipotoxic injury–induced release of hepatocyte exosomes enriched with miR‐192‐5p played a critical role in the activation of M1 macrophages and hepatic inflammation. Serum miR‐192‐5p levels in patients with NAFLD positively correlated with hepatic inflammatory activity score and disease progression. Similarly, the serum miR‐192‐5p level and the number of M1 macrophages, as well as the expression levels of the hepatic proinflammatory mediators, were correlated with disease progression in high‐fat high‐cholesterol diet–fed rat models. Lipotoxic hepatocytes released more miR‐192‐5p‐enriched exosomes than controls, which induced M1 macrophage (cluster of differentiation 11b–positive CD11b+/CD86+) activation and increase of inducible nitric oxide synthase, interleukin 6, and tumor necrosis factor alpha expression. Furthermore, hepatocyte‐derived exosomal miR‐192‐5p inhibited the protein expression of the rapamycin‐insensitive companion of mammalian target of rapamycin (Rictor), which further inhibited the phosphorylation levels of Akt and forkhead box transcription factor O1 (FoxO1) and resulted in activation of FoxO1 and subsequent induction of the inflammatory response.
Conclusions
Hepatocyte‐derived exosomal miR‐192‐5p plays a critical role in the activation of proinflammatory macrophages and disease progression of NAFLD through modulating Rictor/Akt/FoxO1 signaling. Serum exosomal miR‐192‐5p represents a potential noninvasive biomarker and therapeutic target for nonalcoholic steatohepatitis.
•Microplastics from biodegradable polyester were observed in both freahwater and seawater.•UV radiation, simulating the sunlight, promoted the microplastic formation .•Microplastics showed fiber, ...rod-like and spherical shapes.•More microplastics from biodegradable polymer than non-biodegradable polymer were observed.
Biodegradable polymers have been regarded as a promising solution to tackle the pollutions caused by the wide use of conventional polymers. However, during the biodegradation process, the material fragmentation leads to microplastics. In this work, the formation of microplastics from biodegradable poly (butylene adipate-co-terephthalate) (PBAT) in different aquatic environments was investigated and compared with the common non-biodegradable low-density polyethylene (LDPE). The results showed that a much larger quantity of plastic fragments/particles were formed in all aquatic environments from PBAT than from LDPE. In addition, UV-A pretreatment, simulating the exposure to sunlight, increased the rate of PBAT microplastic formation significantly. The size distribution and shapes of the formed microplastics were systematically studied, along with changes in the polymer physicochemical properties such as molecular weight, thermal stability, crystallinity, and mechanical properties, to reveal the formation process of microplastics. This study shows that the microplastic risk from biodegradable polymers is high and needs to be further evaluated with regards to longer timeframes, the biological fate of intermediate products, and final products in freshwater, estuarine and seawater natural habitats. Especially, considering that these microplastics may have good biodegradability in warmer 20 – 25° water but will most likely be highly persistent in the world's cold deep seas.
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Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Exercise has been associated with beneficial effects in patients ...with CKD. Here we show that the induction of a myokine, irisin, improves kidney energy metabolism and prevents kidney damage. In response to kidney injury, mice with muscle-specific PGC-1α overexpression (mPGC-1α) exhibit reduced kidney damage and fibrosis. Metabolomics analysis reveals increased ATP production and improved energy metabolism in injured kidneys from mPGC-1α mice. We identify irisin as a serum factor that mediates these metabolic effects during progressive kidney injury by inhibiting TGF-β type 1 receptor. Irisin depletion from serum blunts the induction of oxygen consumption rate observed in tubule cells treated with mPGC-1α serum. In mice, recombinant irisin administration attenuates kidney damage and fibrosis and improves kidney functions. We suggest that myokine-mediated muscle-kidney crosstalk can suppress metabolic reprograming and fibrogenesis during kidney disease.
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