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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.

Catalytic peroxymonosulfate (PMS) activation processes don’t solely rely on electron transfer from dominant metal centers due to the complicated composition and interface environment of catalysts. Herein the synthesis of a cobalt based metal-organic framework containing polyvanadate [V 4 O 12 ] 4− cluster, Co 2 (V 4 O 12 )(bpy) 2 (bpy = 4,4’-bipyridine), is presented. The catalyst demonstrates superior degradation activity toward various micropollutants, with higher highest occupied molecular orbital (HOMO), via nonradical attack. The X-ray absorption spectroscopy and density functional theory (DFT) calculations demonstrate that Co sites act as both PMS trapper and electron donor. In situ spectral characterizations and DFT calculations reveal that the terminal oxygen atoms in the [V 4 O 12 ] 4− electron sponge could interact with the terminal hydrogen atoms in PMS to form hydrogen bonds, promoting the generation of SO 5 * intermediate via both dynamic pull and direct electron transfer process. Further, Co 2 (V 4 O 12 )(bpy) 2 exhibits long-term water purification ability, up to 40 h, towards actual wastewater discharged from an ofloxacin production factory. This work not only presents an efficient catalyst with an electron sponge for water environmental remediation via nonradical pathway, but also provides fundamental insights into the Fenton-like reaction mechanism. Peroxymonosulfate (PMS) activation might not solely rely on electron transfer from dominant metal centers. Here, authors found that the formation of hydrogen bond between PMS and [V 4 O 12 ] 4− in Co 2 (V 4 O 12 )(bpy) 2 catalyst provided extra electron transfer channel for achieving efficient PMS activation.

HighlightsDrawing wisdom and inspiration from nature, an eco-mimetic nanoarchitecture is constructed, featuring tunable electromagnetic properties and high-efficiency energy attenuation.Through in-depth insight into the microstructure, the material basis of electromagnetic response is clearly revealed to establish an intrinsic connection between microscopic electronic structure and macroscopic electromagnetic properties.A creative self-powered energy conversion device is constructed, with the integrated functions including electromagnetic protection and waste energy recycling, which offers a new horizon for the fields of energy and environment.Advanced electromagnetic devices, as the pillars of the intelligent age, are setting off a grand transformation, redefining the structure of society to present pluralism and diversity. However, the bombardment of electromagnetic radiation on society is also increasingly serious along with the growing popularity of \"Big Data\". Herein, drawing wisdom and inspiration from nature, an eco-mimetic nanoarchitecture is constructed for the first time, highly integrating the advantages of multiple components and structures to exhibit excellent electromagnetic response. Its electromagnetic properties and internal energy conversion can be flexibly regulated by tailoring microstructure with oxidative molecular layer deposition (oMLD), providing a new cognition to frequency-selective microwave absorption. The optimal reflection loss reaches ≈  − 58 dB, and the absorption frequency can be shifted from high frequency to low frequency by increasing the number of oMLD cycles. Meanwhile, a novel electromagnetic absorption surface is designed to enable ultra-wideband absorption, covering almost the entire K and Ka bands. More importantly, an ingenious self-powered device is constructed using the eco-mimetic nanoarchitecture, which can convert electromagnetic radiation into electric energy for recycling. This work offers a new insight into electromagnetic protection and waste energy recycling, presenting a broad application prospect in radar stealth, information communication, aerospace engineering, etc.

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.

Transforming growth factor‐β (TGF‐β) and programmed death ligand 1 (PD‐L1) initiate signaling pathways with complementary, nonredundant immunosuppressive functions in the tumor microenvironment (TME). In the TME, dysregulated TGF‐β signaling suppresses antitumor immunity and promotes cancer fibrosis, epithelial‐to‐mesenchymal transition, and angiogenesis. Meanwhile, PD‐L1 expression inactivates cytotoxic T cells and restricts immunosurveillance in the TME. Anti‐PD‐L1 therapies have been approved for the treatment of various cancers, but TGF‐β signaling in the TME is associated with resistance to these therapies. In this review, we discuss the importance of the TGF‐β and PD‐L1 pathways in cancer, as well as clinical strategies using combination therapies that block these pathways separately or approaches with dual‐targeting agents (bispecific and bifunctional immunotherapies) that may block them simultaneously. Currently, the furthest developed dual‐targeting agent is bintrafusp alfa. This drug is a first‐in‐class bifunctional fusion protein that consists of the extracellular domain of the TGF‐βRII receptor (a TGF‐β ‘trap’) fused to a human immunoglobulin G1 (IgG1) monoclonal antibody blocking PD‐L1. Given the immunosuppressive effects of the TGF‐β and PD‐L1 pathways within the TME, colocalized and simultaneous inhibition of these pathways may potentially improve clinical activity and reduce toxicity. The TGF‐β and PD‐L1 signaling pathways have complementary, nonredundant functions in the tumor microenvironment. Dysregulated TGF‐β signaling suppresses antitumor immunity and promotes cancer fibrosis, epithelial–mesenchymal transition, and angiogenesis, while PD‐L1 restricts immunosurveillance. We review existing strategies for simultaneous inhibition of these pathways, highlighting dual‐targeting agents that may provide colocalized, simultaneous inhibition.

In the increasingly perfect underground garage construction process, the underground garage entrance water blocking problem is getting more and more attention. This paper proposes a kind of air wall water-blocking device applied to underground garage. The device is installed on the side of the straight and curved paths at the entrances and exits of the spiral underground garage. It utilizes two fans to blow the water to the drain on the other side to achieve unobstructed access to stop the water. In this paper, CFD simulation is firstly carried out on the straight road of the spiral underground garage to verify the feasibility of the program. The accuracy of the simulation results was verified by building a straight road model and conducting experiments. After that, an equal-scale 3D model of the spiral underground garage was built. Orthogonal experiments on the effects of inlet water flow velocity, fan wind speed at the straight road and fan wind speed at the curved road on the water blocking effect were carried out by using CFD simulation. A preliminary range of water velocity of 2.250 m/min to 6.786 m/min was obtained experimentally, and this range of water velocity was used as an input parameter for the simulation. The results show that the speed of water flow at the entrance of the garage and the wind speed of the fan at the straight road have a greater effect on the water blocking effect than the wind speed of the fan at the curved road. When the wind speed of the fan at the straight road is 25m/s, proper adjustment of the wind speed of the fan at the curved road can realize a good water-blocking effect of the spiral underground garage entrance within the range of water flow rate of 2.250m/min ~ 6.786m/min. Therefore, in the practical application of using the air wall water blocking scheme to realize the underground garage entrance water blocking strategy is to give priority to improve the wind speed of the fan at the straight road to improve the effect of water blocking.

The comorbidity of depression and addiction has become a serious public health issue, and the relationship between these two disorders and their potential mechanisms has attracted extensive attention. Numerous studies have suggested that depression and addiction share common mechanisms and anatomical pathways. The nucleus accumbens (NAc) has long been considered a key brain region for regulating many behaviors, especially those related to depression and addiction. In this review, we focus on the association between addiction and depression, highlighting the potential mediating role of the NAc in this comorbidity via regulation of changes in neural circuits and molecular signaling. To clarify the mechanisms underlying this association, we summarize evidence from overlapping reward neurocircuitry, the resemblance of cellular and molecular mechanisms, and common treatments. Understanding the interplay between these disorders should help guide comorbidity clinical prevention and search for a new target for comorbidity treatment.

Vision transformers (ViTs) are increasingly utilized for HSI classification due to their outstanding performance. However, ViTs encounter challenges in capturing global dependencies among objects of varying sizes, and fail to effectively exploit the spatial–spectral information inherent in HSI. In response to this limitation, we propose a novel solution: the multi-scale spatial–spectral transformer (MSST). Within the MSST framework, we introduce a spatial–spectral token generator (SSTG) and a token fusion self-attention (TFSA) module. Serving as the feature extractor for the MSST, the SSTG incorporates a dual-branch multi-dimensional convolutional structure, enabling the extraction of semantic characteristics that encompass spatial–spectral information from HSI and subsequently tokenizing them. TFSA is a multi-head attention module with the ability to encode attention to features across various scales. We integrated TFSA with cross-covariance attention (CCA) to construct the transformer encoder (TE) for the MSST. Utilizing this TE to perform attention modeling on tokens derived from the SSTG, the network effectively simulates global dependencies among multi-scale features in the data, concurrently making optimal use of spatial–spectral information in HSI. Finally, the output of the TE is fed into a linear mapping layer to obtain the classification results. Experiments conducted on three popular public datasets demonstrate that the MSST method achieved higher classification accuracy compared to state-of-the-art (SOTA) methods.

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal–organic framework with the formula of [Zn6(NDA)6(DPBT)3] 2H2O·3DMFn (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.