Integrating multifunctionality such as stretchability, adhesiveness, and electroconductivity on a single protein hydrogel is highly desirable for various applications, and remains a challenge. Here ...we present the development of such multifunctional hydrogels based on resilin, a natural rubber-like material with remarkable extensibility and resilience. First, genetically engineered reslin-like proteins (RLPs) with varying molecular weight were biosynthesized to tune mechanical strength and stiffness of the cross-linked RLP hydrogels. Second, glycerol was incorporated into the hydrogels to endow adhesive properties. Next, a graphene–RLP conjugate was synthesized for cross-linking with the unmodified, pristine RLP to form an integrated network. The obtained hybrid hydrogel could be stretched to over four times of its original length, and self-adhered to diverse substrate surfaces due to its high adhesion strength of ∼24 kPa. Furthermore, the hybrid hydrogel showed high sensitivity, with a gauge factor of 3.4 at 200% strain, and was capable of real-time monitoring human activities such as finger bending, swallowing, and phonating. Due to these favorable attributes, the graphene/resilin hybrid hydrogel was a promising material for use in wearable sensors. In addition, the above material design and functionalization strategy may provide intriguing opportunities to generate innovative materials for broad applications.
Soft robots capable of efficiently implementing tasks in fluid-immersed environments hold great promise for diverse applications. However, it remains challenging to achieve robotization that relies ...on dynamic underwater adhesion and morphing capability. Here we propose the construction of such robots with designer protein materials. Firstly, a resilin-like protein is complexed with polyoxometalate anions to form hydrogels that can rapidly switch between soft adhesive and stiff non-adhesive states in aqueous environments in response to small temperature variation. To realize remote control over dynamic adhesion and morphing, Fe
O
nanoparticles are then integrated into the hydrogels to form soft robots with photothermal and magnetic responsiveness. These robots are demonstrated to undertake complex tasks including repairing artificial blood vessel, capturing and delivering multiple cargoes in water under cooperative control of infrared light and magnetic field. These findings pave an avenue for the creation of protein-based underwater robots with on-demand functionalities.
Background
The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to ...investigate the clinical characteristics of COVID‐19 children with different severities and allergic status.
Methods
Data extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID‐19 children, were summarized and analyzed.
Results
The median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10, and TNF‐α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels.
Conclusion
Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID‐19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.
There is no difference between allergic and nonallergic children in clinical features and laboratory/immunological findings, and allergy is not a risk factor for COVID‐19. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) was observed. Higher proportion of patients with pneumonia have fever, cough, comorbidities, and increased inflammatory biomarkers (procalcitonin, alkaline phosphatase and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10, and TNF‐α) than those without pneumonia. Abbreviations: AD, atopic dermatitis; AR, allergic rhinitis; AST, aspartate aminotransferase, AURI, acute upper respiratory infection; COVID‐19, coronavirus disease 2019; DA, drug allergy; FA, food allergy; PCT, procalcitonin; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor.
Abstract
Background
Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex ...mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX in oxygen and glucose deprivation (OGD)-treated hepatocytes and its underlying mechanism.
Methods
In order to investigate the function of DEX in liver injury, WRL-68 cells were treated with OGD. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Inflammatory cytokines levels were measured by ELISA assay. The interaction between miR-194 and TUG1 or SIRT1 was detected by dual-luciferase reporter. Gene and protein levels were measured by qPCR or western blotting.
Results
DEX notably reversed OGD-induced inflammation and apoptosis in WRL-68 cell. Meanwhile, the effect of OGD on TUG1, SIRT1 and miR-194 expression in WRL-68 cells was reversed by DEX treatment. However, TUG1 knockdown or miR-194 overexpression reversed the function of DEX in OGD-treated WRL-68 cells. Moreover, TUG1 could promote the expression of SIRT1 by sponging miR-194. Furthermore, knockdown of TUG1 promoted OGD-induced cell growth inhibition and inflammatory responses, while miR-194 inhibitor or SIRT1 overexpression partially reversed this phenomenon.
Conclusions
DEX could suppress OGD-induced hepatocyte apoptosis and inflammation by mediation of TUG1/miR-194/SIRT1 axis. Therefore, this study might provide a scientific basis for the application of DEX on liver injury treatment.
Astrocytes are crucial regulators in the central nervous system. Abnormal activation of astrocytes contributes to some behavior deficits. However, mechanisms underlying the effects remain unclear. ...Here, we studied the activation of A1 astrocytes and their contribution to murine behavior deficits.
A1 astrocytes were induced by treatment with lipopolysaccharide (LPS) in vitro. The functional phenotype of astrocytes was determined by quantitative RT-PCR, ELISA, and immunohistochemistry. To assess the role of A1 astrocytes in vivo, mice were injected intraperitoneally with LPS. Then, murine behaviors were tested, and the hippocampus and cortex were analyzed by quantitative RT-PCR, ELISA, and immunohistochemistry. The function of IL-10 and fluorocitrate on A1 astrocyte activation was also examined.
Our results show that astrocytes isolated from B6.129S6-Il10
/J homozygotes (IL-10
) were prone to characteristics of A1 reactive astrocytes. Compared with their wild-type counterparts, IL-10
astrocytes exhibited higher expression of glial fibrillary acidic protein (GFAP). Whether or not they were stimulated with LPS, IL-10
astrocytes exhibited enhanced expression of A1-specific transcripts and proinflammatory factors IL-1β, IL-6, and TNFα. In addition, IL-10
astrocytes demonstrated hyperphosphorylation of STAT3. Moreover, astrocytes from IL-10
mice showed attenuated phagocytic ability and were neurotoxic. IL-10
mice demonstrated increased immobility time in the forced swim test and defective learning and memory behavior in the Morris water maze test. Moreover, enhanced neuroinflammation was found in the hippocampus and cortex of IL-10
mice, accompanying with more GFAP-positive astrocytes and severe neuron loss in the hippocampus. Pretreatment IL-10
mice with IL-10 or fluorocitrate decreased the expression of proinflammatory factors and A1-specific transcripts in the hippocampus and cortex, and then alleviated LPS-induced depressive-like behavior.
These results demonstrate that astrocytes isolated from B6.129S6-Il10
/J homozygotes are prone to A1 phenotype and contribute to the depression-like behavior and memory deficits. Inhibiting A1 astrocyte activation may be an attractive therapeutic strategy in some neurodegenerative diseases.
Electrostatic interaction is a promising mechanism to expand the range of physiochemical properties of hydrogel materials. However, the versatility of such materials is still limited because of the ...difficulties associated with harnessing strong electrostatic interactions for controllable hydrogel formation. Here we report a modular approach for programming interactions between positively charged biopolymers and polyoxometalate (POM) anions to create dynamic hydrogels. Fabrication of diverse hydrogels was achieved simply by soaking primary networks with predispersed chitosan in aqueous solutions of POMs with various nuclearity and charges. This resulted in double network (DN) hydrogels with 2–3 orders of magnitude higher toughness compared with the precedent composite hydrogels. In addition, the dynamic electrostatic interactions endowed the DN hydrogels reversible responsiveness and intriguing capabilities to memorize shapes, to actuate, and to change colors upon exposure to specific external cues, which are challenging to achieve in previous hydrogels. Furthermore, the flexibility of our approach is demonstrated by the use of either physically or chemically cross-linked primary networks, which are composed of synthetic polymers, natural biopolymers, and even genetically engineered protein polymers. Consequently, our facile and modular approach establishes new opportunities in design and fabrication of dynamic functional hydrogels for wide applications.
We present new laser ablation (LA)‐multicollector‐inductively coupled plasma mass spectrometry detrital zircon U‐Pb age and Hf isotope data of the Triassic sedimentary rocks from the eastern and ...western sides of the Ailaoshan suture in SW China, which separate the Indochina and South China blocks. Detrital zircon grains of the Lower‐Middle Triassic sequences from western South China show single age population of 280–237 Ma (peak at 254–251 Ma) with mainly positive εHf(t) values (+0.15 to +9.11, ~60%). The Middle Triassic samples from eastern Indochina also contain single age population of 273–236 Ma (peak at 246–242 Ma), but with mainly negative εHf(t) values (−18.95 to −1.83, ~88%). The unimodal detrital zircon age pattern and Hf isotope features suggest that the Permian‐Triassic magmatic arcs had supplied detritus for the Lower‐Middle Triassic sequences on both sides of the Ailaoshan suture. In contrast, the Upper Triassic sequences on the either side of the suture display similar polymodal age populations at 290–230, 500–400, 850–700, 1000–900, 2000–1800, and 2600–2400 Ma. This indicates a dramatic change in detrital provenance across the Middle‐Late Triassic boundary. We interpret this change to be resulted from the closure of the Paleotethyan Ailaoshan Ocean in the early Late Triassic. The ocean closure and consequent Indochina‐South China continent‐continent collision may have connected the drainage systems of the two blocks, leading to the marked similarities in their post‐Middle Triassic sedimentary provenance.
Key Points
Lower‐Middle Triassic sedimentary rocks received detritus from Permian‐Triassic magmatic arcs
Upper Triassic sedimentary rocks received detritus from both the Indochina‐South China interior and the Permian‐Triassic magmatic arcs
Final closure of the Ailaoshan Ocean was likely completed by the Late Triassic
Protein condensates are distinct structures assembled in living cells that concentrate molecules via phase separation in a confined subcellular compartment. In the past decade, remarkable advances ...have been made to discover the fundamental roles of the condensates in spatiotemporal control of cellular metabolism and physiology and to reveal the molecular principles, components and driving forces that underlie their formation. Here we review the unique properties of the condensates, the promise and hurdles for harnessing them toward purposeful design and manipulation of biological functions in living cells. In particular, we highlight recent advances in mining and understanding the proteinaceous components for creating designer condensates, along with the engineering approaches to manipulate their material properties and biological functions. With these advances, a greater variety of complex organelle-like structures can be built for diverse applications, with unprecedented effects on synthetic biology.
Metal oxides have attracted renewed interest as promising electrode materials for high energy density supercapacitors. However, the electrochemical performance of metal oxide materials deteriorates ...significantly with the increase of mass loading due to their moderate electronic and ionic conductivities. This limits their practical energy. Herein, we perform a morphology and phase-controlled electrodeposition of MnO2 with ultrahigh mass loading of 10 mg cm–2 on a carbon cloth substrate to achieve high overall capacitance without sacrificing the electrochemical performance. Under optimum conditions, a hierarchical nanostructured architecture was constructed by interconnection of primary two-dimensional ε-MnO2 nanosheets and secondary one-dimensional α-MnO2 nanorod arrays. The specific hetero-nanostructures ensure facile ionic and electric transport in the entire electrode and maintain the structure stability during cycling. The hierarchically structured MnO2 electrode with high mass loading yields an outstanding areal capacitance of 3.04 F cm–2 (or a specific capacitance of 304 F g–1) at 3 mA cm–2 and an excellent rate capability comparable to those of low mass loading MnO2 electrodes. Finally, the aqueous and all-solid asymmetric supercapacitors (ASCs) assembled with our MnO2 cathode exhibit extremely high volumetric energy densities (8.3 mWh cm–3 at the power density of 0.28 W cm–3 for aqueous ASC and 8.0 mWh cm–3 at 0.65 W cm–3 for all-solid ASC), superior to most state-of-the-art supercapacitors.
Spatially directed synthesis of quantum dots (QDs) is intriguing yet challenging in organisms, due to the dispersed feature of templating biomolecules and precursors. Whether this task could be ...accomplished by biomolecular condensates, an emerging type of membraneless compartments in cells remains unknown. Here we report synthetic protein condensates for templated synthesis of QDs in bacterium Escherichia coli. This was realized by overexpression of spider silk protein to bind precursor ions and recruit other necessary components, which induced the spidroin to form more β‐sheet structures for assembly and maturation of the protein condensates. This in turn enabled formation and co‐localization of the fluorescent QDs to “light up” the condensates, and alleviated cytotoxicity of the precursor heavy metal ions and resulting QDs. Thus, our results suggest a new strategy for nanostructure synthesis and deposition in subcellular compartments with great potential for in situ applications.
Presented herein is a novel strategy for spatially confined biosynthesis of quantum dots in bacterium by using biomolecular condensates formed by liquid‐liquid phase separation of recombinant spider silk protein. This provides a previously unprecedented access to compartmentalized nanostructure synthesis within living cells with great potential for in situ applications.
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