A protein‐sized (ca. 4.2×4.2×3.6 nm3) non‐biologically derived molecule {Nb288O768(OH)48(CO3)12} (Nb288) containing up to 288 niobium atoms has been obtained, which is by far the largest and the ...highest nuclearity polyoxoniobate (PONb). Particularly, in terms of metal nuclearity number, Nb288 is the second largest cluster so far reported in classic polyoxometalate chemistry (V, Mo, W, Nb, and Ta). Nb288 can be described as a giant windmill‐like cluster aggregate of six nanoscale high‐nuclearity PONb units {Nb47O128(OH)6(CO3)2} (Nb47) joined together by six additional Nb ions. Interestingly, the 47‐nuclearity Nb47 units generated in situ can be isolated and bridged by copper complexes to form an inorganic–organic hybrid three‐dimensional PONb framework, which exhibits effective catalytic activity for hydrolyzing nerve agent simulant of dimethyl methylphosphonate. The unique Nb47 cluster also provides a new type of topology to very limited family of Nb‐O clusters.
Friendly niobium giant: An unprecedentedly huge polyoxoniobate (PONb) with as many as 288 Nb centers has been made. This is by far the largest PONb and the second highest nuclearity polyoxometalate reported to date. It incorporates a unique 47‐nuclearity PONb building unit formed in situ, which can be stabilized by metal complexes to form an extended PONb framework with the capability of hydrolyzing dimethyl methylphosphonate.
Nonalcoholic fatty liver disease (NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide ...spectrum of conditions, ranging from fatty liver - which generally follows a benign, non-progressive clinical course - to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.
Atomic‐molecular engineering is an effective way to accurately tailor the microstructures and components of materials at the micro‐nano scale, which can be applied to flexibly manipulate their ...electromagnetic (EM) response. Herein, graphene microlaminates with multi‐layer structure are fabricated by atomic cluster engineering and oxidative molecular layer deposition for the first time. The microlaminates enable a tunable EM loss (from 0.93 to 3.94 for imaginary permittivity and from 0.17 to 0.25 for imaginary permeability) by changing poly(3,4‐ethylenedioxythiophene) cycles, and the attenuation constant reaches 160. On this basis, multifunctional antennas are conceived, achieving frequency‐selective response that enables steady harvest of > 90% of EM energy from signal source, and tactfully recycling waste heat energy and mechanical energy. This study will furnish a new horizon for information transmission and artificial intelligence in the future.
Atomic‐molecular engineering is employed to fabricate graphene microlaminate with multi‐layer structure. The microlaminate exhibits excellent electromagnetic losses and high energy attenuation. Importantly, multifunctional antenna is further conceived, with integrated functions including frequency‐selective response and waste energy recycling, which will promote the development of an intelligent society.
Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively ...inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering the potential advantage of home administration without hospital admission, in patients with platinum-resistant or platinum-refractory ovarian cancer.
In this phase 2, single-arm, prospective study, we recruited patients aged 18–70 years with platinum-resistant or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1. We used Simon's two-stage design, and analysed efficacy in the intention-to-treat and per-protocol populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but excluded those without any safety data. This study is registered with ClinicalTrials.gov, number NCT02867956.
Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date (Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective responses were achieved in 19 (54%; 95% CI 36·6–71·2) of 35 patients in the intention-to-treat population and in 19 (61%; 42·2–78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were neutropenia (17 50%), fatigue (11 32%), anaemia (ten 29%), and mucositis (eight 24%). Serious adverse events were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient had increased ascites due to disease progression). No treatment-related deaths were recorded.
The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted.
None.
Lightweight and flexible electronic materials with high energy attenuation hold an unassailable position in electromagnetic stealth and intelligent devices. Among them, emerging heterodimensional ...structure draws intensive attention in the frontiers of materials, chemistry, and electronics, owing to the unique electronic, magnetic, thermal, and optical properties. Herein, an intrinsic heterodimensional structure consisting of alternating assembly of 0D magnetic clusters and 2D conductive layers is developed, and its macroscopic electromagnetic properties are flexibly designed by customizing the number of oxidative molecular layer deposition (oMLD) cycles. This unique heterodimensional structure features highly ordered spatial distribution, with an achievement of electron-dipole and magnetic-dielectric double synergies, which exhibits the high attenuation of electromagnetic energy (160) and substantial improvement of dielectric loss tangent (≈200%). It can respond to electromagnetic waves of different bands to achieve multispectral stealth, covering visible light, infrared radiation, and gigahertz wave. Importantly, two kinds of ingenious information interaction devices are constructed with heterodimensional structure. The hierarchical antennas allow precise targeting of operating bands (S- to Ku- bands) by oMLD cycles. The strain imaging device with high sensitivity opens a new horizon for visual interaction. This work provides a creative insight for developing advanced micro-nano materials and intelligent devices.
A series containing the highest nuclearity polyoxoniobate (PONb) nanoclusters, ranging from dimers to tetramers, has been obtained. They include one 114‐nuclear {Li8⊂Nb114O316}, one 81‐nuclear ...{Li3K⊂Nb81O225}, and one 52‐nuclear {H4Nb52O150}. The Nb nuclearity of these PONbs is remarkably larger than those of all known high‐nuclearity PONbs (≤32). Furthermore, the introduction of 3d Cu2+ ions can lead to the generation of extended inorganic–organic hybrid frameworks built from novel, high‐nuclearity, nanoscale heterometallic PONb building blocks {H3Cu3Nb78O222} or {H3Cu4(en)Nb78O222}. These building blocks also contain the largest number of Nb centers of any heterometallic PONbs reported to date. The synthesis of new‐type PONbs has long been a challenging subject in PONb chemistry.
Big, bigger, biggest: A series of record high‐nuclearity PONbs, ranging from 52‐nuclear {Nb52}, 81‐nuclear {Nb81} to 114‐nuclear {Nb114}, is made. The introduction of 3d Cu2+ ions allows the construction of extended inorganic–organic hybrid PONb frameworks based on giant heterometallic nanoclusters {Cu3Nb78} and {Cu4Nb78}.
•In-situ treatment of site soil using DJM technique and SPC binder is presented.•Solidified/stabilized soil exhibits satisfactory long-term performance after 326 days.•Leached concentrations of heavy ...metals and COD in soil are considerably reduced.•Soil resistance and acid neutralization capacity are remarkably improved.•In-situ field trial coincides well with lab study in strength/leaching properties.
In this study, in-situ treatment using dry jet mixing construction method and SPC (single superphosphate and calcium oxide) new binder are used to solidify/stabilize a heavy metal contaminated site soil with relatively high content of organic matters. Time-dependent field performance of the soils at 41 and 326 days after treatment is evaluated, which includes electrical conductivity (EC), leachability of heavy metals and chemical oxygen demand (COD), soil penetration resistance, acid neutralization capacity (ANC), and chemical speciation of heavy metals. The results indicate that the stabilized soils exhibit satisfactory performance which is comparable with the laboratory study. In-situ SPC treatment significantly decreases EC values and increases penetration resistance values of the soils. Leachability of lead, zinc, cadmium and COD decreases with increasing SPC content or curing time. Large percentages of heave metals in the soils are transformed from exchangeable fractions to residual fractions after treatment. These, coupled with the improved ANC, result in low heavy metal leachability in stabilized soils.
Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein–Barr virus (EBV) infection or reactivation as a trigger ...for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein–Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross‐reactivity between gp350 antibodies and SADs‐associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.
CYP51 (Erg11) belongs to the cytochrome P450 monooxygenase (CYP) superfamily and mediates a crucial step of the synthesis of ergosterol, which is a fungal-specific sterol. It is also the target of ...azole drugs in clinical practice. In recent years, researches on fungal CYP51 have stepped into a new stage attributing to the discovery of crystal structures of the homologs in
and
. This review summarizes the functions, structures of fungal CYP51 proteins, and the inhibitors targeting these homologs. In particular, several drug-resistant mechanisms associated with the fungal CYP51s are introduced. The sequences and crystal structures of CYP51 proteins in different fungal species are also compared. These will provide new insights for the advancement of research on antifungal agents.
Cytokines play crucial roles in orchestrating complex multicellular interactions between pancreatic β cells and immune cells in the development of type 1 diabetes (T1D) and are thus potential ...immunotherapeutic targets for this disorder. Cytokines that can induce regulatory functions—for example, IL‐10, TGF‐β and IL‐33—are thought to restore immune tolerance and prevent β‐cell damage. By contrast, cytokines such as IL‐6, IL‐17, IL‐21 and TNF, which promote the differentiation and function of diabetogenic immune cells, are thought to lead to T1D onset and progression. However, targeting these dysregulated cytokine networks does not always result in consistent effects because anti‐inflammatory or proinflammatory functions of cytokines, responsible for β‐cell destruction, are context dependent. In this review, we summarise the current knowledge on the involvement of well‐known cytokines in both the initiation and destruction phases of T1D and discuss advances in recently discovered roles of cytokines. Additionally, we emphasise the complexity and implications of cytokine modulation therapy and discuss the ways in which this strategy has been translated into clinical trials.
Cytokines have been directly implicated in the pathogenesis of type 1 diabetes (T1D) via orchestrating complex multicellular interactions between pancreatic β cells and immune cells, and are thus potential immunotherapeutic targets for this disorder. In this review, we discuss the pleiotropic roles of cytokines, which determine whether a pathological or protective immune response occurs in both the initiation and destruction phases of T1D. We also discuss potential implications of cytokines in the deployment of immunotherapeutic strategies for T1D.
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