Data intensive analysis is the major challenge in smart cities because of the ubiquitous deployment of various kinds of sensors. The natural characteristic of geodistribution requires a new computing ...paradigm to offer location-awareness and latency-sensitive monitoring and intelligent control. Fog Computing that extends the computing to the edge of network, fits this need. In this paper, we introduce a hierarchical distributed Fog Computing architecture to support the integration of massive number of infrastructure components and services in future smart cities. To secure future communities, it is necessary to integrate intelligence in our Fog Computing architecture, e.g., to perform data representation and feature extraction, to identify anomalous and hazardous events, and to offer optimal responses and controls. We analyze case studies using a smart pipeline monitoring system based on fiber optic sensors and sequential learning algorithms to detect events threatening pipeline safety. A working prototype was constructed to experimentally evaluate event detection performance of the recognition of 12 distinct events. These experimental results demonstrate the feasibility of the system's city-wide implementation in the future.
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•Detailed role that nanotechnology can play in addressing this pandemic.•Using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation ...pathway.•Introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery.•Designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle.•Promoting the utilization of nanomaterials in pneumonia treatment.
In just a few months, SARS-CoV-2 and the disease it causes, COVID-19, created a worldwide pandemic. Virologists, biologists, pharmacists, materials scientists, and clinicians are collaborating to develop efficient treatment strategies. Overall, in addition to the use of clinical equipment to assist patient rehabilitation, antiviral drugs and vaccines are the areas of greatest focus. Given the physical size of SARS-CoV-2 and the vaccine delivery platforms currently in clinical trials, the relevance of nanotechnology is clear, and previous antiviral research using nanomaterials also supports this connection. Herein we briefly summarize current representative strategies regarding nanomaterials in antiviral research. We focus specifically on SARS-CoV-2 and the detailed role that nanotechnology can play in addressing this pandemic, including i) using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway; ii) introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery; iii) designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle; and iv) promoting the utilization of nanomaterials in pneumonia treatment.
The great success achieved by the two highly-effective messenger RNA (mRNA) vaccines during the COVID-19 pandemic highlights the great potential of mRNA technology. Through the evolution of mRNA ...technology, chemistry has played an important role from mRNA modification to the synthesis of mRNA delivery platforms, which allows various applications of mRNA to be achieved both
in vitro
and
in vivo
. In this tutorial review, we provide a summary and discussion on the significant progress of emerging mRNA technologies, as well as the underlying chemical designs and principles. Various nanoparticle (NP)-based delivery strategies including protein-mRNA complex, lipid-based carriers, polymer-based carriers, and hybrid carriers for the efficient delivery of mRNA molecules are presented. Furthermore, typical mRNA delivery platforms for various biomedical applications (
e.g.
, functional protein expression, vaccines, cancer immunotherapy, and genome editing) are highlighted. Finally, our insights into the challenges and future development towards clinical translation of these mRNA technologies are provided.
This review highlights significant progress in mRNA delivery platforms and therapeutic applications from the view of chemistry. Insights into the challenges and future development towards clinical translation of mRNA therapeutics are also provided.
Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched ...structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently "capture" the ultrathin and biocompatible FCLs (MgO and Fe
O
) sandwiched between two identical tetrahedral layers (SiO
and Al
O
) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from -0.4 eV to -0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs.
The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial ...infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic “skin” to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug “reservoir” to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for “on-demand” pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challengingwound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment.
A simple, noncovalent modification strategy was proposed to synthesize poly-l-lysine-black phosphorus (pLL-BP) hybrid. BP nanoflakes were prepared with a water-phase exfoliation method. pLL can ...adhere to the surface of BP via hydrophobic interaction between butyl chains of pLL and the BP surface as well as the electrostatic interaction between the protonated amino groups on pLL and the negative charge on deprotonated PxOy groups remaining on BP. The as-synthesized pLL-BP hybrid turns out to be an ideal matrix for hemoglobin immobilization and direct electron transfer. Good conductivity and biocompatibility of BP maintain the native structure and the bioactivity of hemoglobin (Hb), facilitating the direct electron transfer between the electroactive center of Hb and electrode. The rate constant (k ET) for direct electron transfer of Hb@pLL-BP is calculated to be 11.24 s–1. The constructed Hb-pLL-BP based enzymatic electrochemical biosensor displays excellent catalytic activity toward the reduction of oxygen and hydrogen peroxide. The electrochemical response toward H2O2 exhibits a linear dependence on hydrogen peroxide concentration ranging between 10 μM and 700 μM. The results demonstrate that the pLL-BP hybrid can act as a biocompatible building block for the construction of novel biofuel cells, bioelectronics, and biosensors.
In multi-modal multi-agent trajectory forecasting, two major challenges have not been fully tackled: 1) how to measure the uncertainty brought by the interaction module that causes correlations among ...the predicted trajectories of multiple agents; 2) how to rank the multiple predictions and select the optimal predicted trajectory. In order to handle the aforementioned challenges, this work first proposes a novel concept, collaborative uncertainty (CU), which models the uncertainty resulting from interaction modules. Then we build a general CU-aware regression framework with an original permutation-equivariant uncertainty estimator to do both tasks of regression and uncertainty estimation. Furthermore, we apply the proposed framework to current SOTA multi-agent multi-modal forecasting systems as a plugin module, which enables the SOTA systems to 1) estimate the uncertainty in the multi-agent multi-modal trajectory forecasting task; 2) rank the multiple predictions and select the optimal one based on the estimated uncertainty. We conduct extensive experiments on a synthetic dataset and two public large-scale multi-agent trajectory forecasting benchmarks. Experiments show that: 1) on the synthetic dataset, the CU-aware regression framework allows the model to appropriately approximate the ground-truth Laplace distribution; 2) on the multi-agent trajectory forecasting benchmarks, the CU-aware regression framework steadily helps SOTA systems improve their performances. Especially, the proposed framework helps VectorNet improve by 262 cm regarding the Final Displacement Error of the chosen optimal prediction on the nuScenes dataset; 3) in multi-agent multi-modal trajectory forecasting, prediction uncertainty is proportional to future stochasticity; 4) the estimated CU values are highly related to the interactive information among agents. The proposed framework can guide the development of more reliable and safer forecasting systems in the future. Our code is available at https://github.com/MediaBrain-SJTU/Collaborative-Uncertainty .
Abstract
Background
Triggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various ...neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear.
Method
Genetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied.
Results
We inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio OR per one standard deviation SD increase = 1.064, 95% CI 1.012–1.119,
P
= 0.014,
P
FDR
= 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016–1.072,
P
= 0.002,
P
FDR
= 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes.
Conclusions
Taken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.
The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment. Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; ...however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood. We found that tumor‐associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL‐1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF‐1α). Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL‐1β release by tumor‐associated macrophages with an M2 phenotype. We further confirmed that the necrotic debris–induced IL‐1β secretion was mediated through Toll‐like receptor 4/TIR domain–containing adapter‐inducing interferon‐β/nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide‐induced inflammation. Using mass spectrometry, we identified a group of proteins with O‐linked glycosylation to be responsible for the necrotic debris–induced IL‐1β secretion. Following the increase of IL‐1β in the local microenvironment, the synthesis of HIF‐1α was up‐regulated by IL‐1β in HCC cells through cyclooxygenase‐2. The epithelial–mesenchymal transition of HCC cells was enhanced by overexpression of HIF‐1α. We further showed that IL‐1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients. Conclusion: Our findings revealed an HIF‐1α/IL‐1β signaling loop between cancer cells and tumor‐associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial–mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti‐inflammatory strategy in HCC treatment. (Hepatology 2018;67:1872‐1889)
Backgrounds To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with ...those of TACE alone . Methods A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. Results After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. Conclusion TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients. Keywords: Unresectable hepatocellular carcinoma, Camrelizumab, Transcatheter arterial chemoembolization, Lenvatinib
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