Although polymerase chain reaction (PCR) is the most widely used method for DNA amplification, the requirement of thermocycling limits its non-laboratory applications. Isothermal DNA amplification ...techniques are hence valuable for on-site diagnostic applications in place of traditional PCR. Here we describe a true isothermal approach for amplifying and detecting double-stranded DNA based on a CRISPR-Cas9-triggered nicking endonuclease-mediated Strand Displacement Amplification method (namely CRISDA). CRISDA takes advantage of the high sensitivity/specificity and unique conformational rearrangements of CRISPR effectors in recognizing the target DNA. In combination with a peptide nucleic acid (PNA) invasion-mediated endpoint measurement, the method exhibits attomolar sensitivity and single-nucleotide specificity in detection of various DNA targets under a complex sample background. Additionally, by integrating the technique with a Cas9-mediated target enrichment approach, CRISDA exhibits sub-attomolar sensitivity. In summary, CRISDA is a powerful isothermal tool for ultrasensitive and specific detection of nucleic acids in point-of-care diagnostics and field analyses.
Memristors are emerging as a rising star of new computing and information storage techniques. However, the practical applications are severely challenged by their instability toward harsh conditions, ...including high moisture, high temperatures, fire, ionizing irradiation, and mechanical bending. In this work, for the first time, lead‐free double perovskite Cs2AgBiBr6 is utilized for environmentally robust memristors, enabling highly efficient information storage. The memory performance of the typical indium‐tin‐oxide/Cs2AgBiBr6/Au sandwich‐like memristors is retained after 1000 switching cycles, 105 s of reading, and 104 times of mechanical bending, comparable to other halide perovskite memristors. Most importantly, the memristive behavior remains robust in harsh environments, including humidity up to 80%, temperatures as high as 453 K, an alcohol burner flame for 10 s, and 60Co γ‐ray irradiation for a dosage of 5 × 105 rad (SI), which is not achieved by any other memristors and commercial flash memory techniques. The realization of an environmentally robust memristor from Cs2AgBiBr6 with a high memory performance will inspire further development of robust electronics using lead‐free double perovskites.
Double perovskite Cs2AgBiBr6 is fabricated into an indium tin oxide/Cs2AgBiBr6/Au device for the first time. Ultrastable memristive behavior is obtained owing to the tough crystallinity of Cs2AgBiBr6. Humidity‐, high temperature‐, fire‐, and radiation‐resistant properties of Cs2AgBiBr6‐based devices promote memristive devices to work in harsh environments, where most perovskite‐based devices may fail to work.
Once an emergency event occurs, a reasonable and effective emergency decision should be made within a short time. The emergency decision‐making (EDM) problems which are based on linguistic ...information have become a research focus in recent years. In this paper, to ensure more effective EDM in real‐life circumstances, a novel combined approach is presented by extending the zero‐sum game (ZSG) using best‐worst method (BWM) and Pythagorean fuzzy uncertain linguistic variables (PFULVs). First, the weights of criteria are calculated by the BWM. Then, the payoff evaluations of decision‐makers are expressed by the PFULVs, and the group payoff evaluation matrix is constructed by using the Pythagorean fuzzy uncertain linguistic prioritized weighted averaging operator. After that, the ZSG method is introduced to rank alternative emergency solutions. The new approach helps to express the vagueness of assessment data provided by decision‐makers more precisely in emergency situations. Finally, a real EDM example is presented and a comparison analysis is performed to validate the feasibility and practicability of the proposed BWM‐PFULV‐ZSG method.
Chronic obstructive pulmonary disease (COPD) is an intractable disease involving a sticky mucus layer and nanoagents with mucus‐penetrating capability offer a new way to deliver drugs. However, drug ...release from nanovehicles requires optimization to enhance the therapeutic effects of COPD therapy. Herein, black phosphorus quantum dots (BPQDs) are combined with PEGylated chitosan nanospheres containing the antibiotic amikacin (termed PEG@CS/BPQDs‐AM NPs). As a drug‐delivery system, the hydrophilicity of PEG and positive charge of CS facilitate the penetration of nanovehicles through the mucus layer. The nanovehicles then adhere to the mucous membrane. Furthermore, the BPQDs degrade rapidly into nontoxic PO43− and acidic H+, thereby promoting the dissociation of PEGylated CS nanospheres, accelerating the release of AM, decreasing the vitality of biofilms for ease of eradication. Our results reveal that drug delivery mediated by BPQDs is a feasible and desirable strategy for precision medicine and promising for the clinical therapy of COPD.
A mucus‐penetrating drug‐delivery strategy is designed for the efficient therapy of chronic obstructive pulmonary disease (COPD). After pulmonary aspiration, nanovehicles can penetrate the mucus barrier and adhere onto the mucous membrane. Subsequently, the nanovehicle degrades via the oxidative degradation of BPQDs, releasing the antibiotic amikacin. This suggests that BPQD‐mediated drug release offers a feasible strategy for precision medicine.
Long-Term Efficacy of a Hepatitis E Vaccine Zhang, Jun; Zhang, Xue-Feng; Huang, Shou-Jie ...
The New England journal of medicine,
03/2015, Letnik:
372, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Hepatitis E virus is a common cause of illness worldwide and is associated with severe complications, especially in pregnant women. In this report, the long-term efficacy, immunogenicity, and safety ...of a hepatitis E vaccine are described.
Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide.
1
,
2
HEV infection occurs in two distinct epidemiologic patterns.
3
The most common pattern is waterborne infection, which is caused by HEV genotype 1 or 2 and occurs mainly in resource-limited countries, often in large, protracted outbreaks or in sporadic cases associated with high mortality among pregnant women.
4
–
6
The other pattern is transmission from animals and humans, which is caused by HEV genotype 3 or 4 and occurs widely in both resource-limited and developed countries.
1
,
7
–
9
Rein et al.
10
estimated the incidence of hepatitis E in areas . . .
Analyzing scattered wave to recognize object is of fundamental significance in wave physics. Recently-emerged deep learning technique achieved great success in interpreting wave field such as in ...ultrasound non-destructive testing and disease diagnosis, but conventionally need time-consuming computer postprocessing or bulky-sized diffractive elements. Here we theoretically propose and experimentally demonstrate a purely-passive and small-footprint meta-neural-network for real-time recognizing complicated objects by analyzing acoustic scattering. We prove meta-neural-network mimics a standard neural network despite its compactness, thanks to unique capability of its metamaterial unit-cells (dubbed meta-neurons) to produce deep-subwavelength phase shift as training parameters. The resulting device exhibits the "intelligence" to perform desired tasks with potential to overcome the current limitations, showcased by two distinctive examples of handwritten digit recognition and discerning misaligned orbital-angular-momentum vortices. Our mechanism opens the route to new metamaterial-based deep-learning paradigms and enable conceptual devices automatically analyzing signals, with far-reaching implications for acoustics and related fields.
As a novel member of the two-dimensional nanomaterial family, mono- or few-layer black phosphorus (BP) with direct bandgap and high charge carrier mobility is promising in many applications such as ...microelectronic devices, photoelectronic devices, energy technologies, and catalysis agents. Due to its benign elemental composition (phosphorus), large surface area, electronic/photonic performances, and chemical/biological activities, BP has also demonstrated a great potential in biomedical applications including biosensing, photothermal/photodynamic therapies, controlled drug releases, and antibacterial uses. The nature of the BP–bio interface is comprised of dynamic contacts between nanomaterials (NMs) and biological systems, where BP and the biological system interact. The physicochemical interactions at the nano–bio interface play a critical role in the biological effects of NMs. In this review, we discuss the interface in the context of BP as a nanomaterial and its unique physicochemical properties that may affect its biological effects. Herein, we comprehensively reviewed the recent studies on the interactions between BP and biomolecules, cells, and animals and summarized various cellular responses, inflammatory/immunological effects, as well as other biological outcomes of BP depending on its own physical properties, exposure routes, and biodistribution. In addition, we also discussed the environmental behaviors and potential risks on environmental organisms of BP. Based on accumulating knowledge on the BP–bio interfaces, this review also summarizes various safer-by-design strategies to change the physicochemical properties including chemical stability and nano–bio interactions, which are critical in tuning the biological behaviors of BP. The better understanding of the biological activity of BP at BP–bio interfaces and corresponding methods to overcome the challenges would promote its future exploration in terms of bringing this new nanomaterial to practical applications.
Body burden of mercury has been linked to hypertension in populations exposed to high mercury levels.
We summarized, extracted, and pooled the results of published studies that investigated mercury ...biomarkers and hypertension or blood pressure (BP) measurements to examine this potential relationship.
We searched PubMed, Embase, and TOXLINE and selected studies according to
defined inclusion criteria. Study quality was assessed by the Newcastle-Ottawa scale for cohort and case-control studies and the Quality Assessment Tool for cross-sectional studies. Study estimates were pooled using inverse-variance weighted random-effects models. Dose-response meta-analysis was performed with studies reporting hypertension and systolic BP for at least three mercury categories.
A total of 29 studies were included in the meta-analysis. The pooled odds ratio (OR) for hypertension, comparing the highest and lowest mercury exposure categories, was 1.35 95% confidence interval (CI): 0.99, 1.83 for populations with hair mercury ≥2 μg/g in comparison with the OR of 1.12 (95% CI: 0.82, 1.52) for populations with hair mercury <2 μg/g. Positive associations were also observed for highest versus lowest mercury exposure categories on systolic and diastolic BP. Heterogeneity was observed for mercury species and exposure groups across different studies. Associations estimated using different mercury biomarkers generally agree with each other in the same study. A nonlinear dose-response relationship with an inflection point at 3 μg/g was identified, for both hypertension and systolic BP.
A significant positive association between mercury and hypertension and between mercury and BP was identified. The exposure dose is an important factor in determining the toxic effects of mercury on hypertension. https://doi.org/10.1289/EHP2863.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Black phosphorus nanosheets (BPs) show great potential for various applications including biomedicine, thus their potential side effects and corresponding improvement strategy deserve investigation. ...Here, in vitro and in vivo biological effects of BPs with and without titanium sulfonate ligand (TiL4) modification are investigated. Compared to bare BPs, BPs with TiL4 modification (TiL4@BPs) can efficiently escape from macrophages uptake, and reduce cytotoxicity and proinflammation. The corresponding mechanisms are also discussed. These findings may not only guide the applications of BPs, but also propose an efficient strategy to further improve the biocompatibility of BPs.
Surface modification: The biocompatibilities of bare black phosphorus nanosheets (BPs) and BPs modified by a titanium sulfonate ligand (TiL4@BPs) are different. TiL4@BPs escapes from macrophage uptake and reduces cytotoxicity and proinflammation. Bare BPs trigger inflammatory responses, including an increase in peripheral neutrophils accompanied by elevation of a group of inflammatory cytokines.
Portal vein tumor thrombosis (PVTT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and is therefore associated with poor prognosis. The presence of PVTT ...frequently accompanies substantial hypoxia within the tumor microenvironment, which is suggested to accelerate tumor metastasis, but it is unclear how this occurs. Recent evidence has shown that the hypoxia-inducible factor HIF-1α induces epithelial-to-mesenchymal transition (EMT) in tumor cells to facilitate metastasis. In this study, we investigated whether hypoxia-induced EMT in cancer cells also affects immune cells in the tumor microenvironment to promote immunosuppression. We found that hypoxia-induced EMT increased the expression of the CCL20 cytokine in hepatoma cells. Furthermore, coculture of monocyte-derived macrophages with hypoxic hepatoma cells revealed that the expression of indoleamine 2, 3-dioxygenase (IDO) was induced in monocyte-derived macrophages in a CCL20-dependent manner. In turn, these IDO-expressing monocyte-derived macrophages suppressed T-cell proliferation and promoted the expansion of immunosuppressive regulatory T cells. Moreover, high CCL20 expression in HCC specimens was associated with PVTT and poor patient survival. Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.
PDF
