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Learning from a few examples (one/few-shot learning) on the fly is a key challenge for on-device machine intelligence. We present the first chip-level demonstration of one-shot learning with Stanford Associative memory for Programmable, Integrated Edge iNtelligence via life-long learning and Search (SAPIENS), a resistive random access memory (RRAM)-based non-volatile associative memory (AM) chip that serves as the backend for memory-augmented neural networks (MANNs). The 64-kb fully integrated RRAM-CMOS AM chip performs long-term feature embedding and retrieval, demonstrated on a 32-way one-shot learning task on the Omniglot dataset. Using only one example per class for 32 unseen classes during on-chip learning, SAPIENS achieves 79% measured inference accuracy on Omniglot, comparable to edge software model accuracy using five-level quantization (82%). It achieves an energy efficiency of 118 GOPS/W at 200 MHz for in-memory L1 distance computation and prediction. Multi-bank measurements on the same chip show that increasing the capacity from three banks (24 kb) to eight banks (64 kb) improves the chip accuracy from 73.5% to 79%, while minimizing the accuracy excursion due to bank-to-bank variability.

For a broad range of industrial, service, and household electric vehicles, dynamic charging is a viable option for energy replenishing that could reduce the size of the onboard energy storage, remove range limitations, and increase operating time. For those systems, timely detection of an approaching vehicle and the detection of strong coupling conditions between transmitter and receiver coils are of prime interest. A novel method is proposed in this article, which utilizes the existing embedded primary coil and power electronics modules to establish a precise detection system based on the power footprint of a traveling receiver. Next, a control algorithm is proposed to accurately control charger activation and deactivation time and deliver the required amount of energy during the coils maximum coupling. The proposed sigmoid-curve-based control algorithm achieves a robust, speed-independent, smooth transition between two states while providing fast dynamics for both aligned and misaligned conditions. Finally, a novel approach to test high-speed dynamic charging in laboratory conditions based on the receiver emulator is developed and used for experimental validation. The vehicle detection and control techniques have been validated through simulations and experimentally on a speed-controlled dynamic charging test station for a wide speed range. The proposed method does not require any additional hardware, sensing devices, or high-speed communication between the vehicle and the charging infrastructure.

Ceramic aerogels are attractive candidates for high-temperature thermal insulation, catalysis support, and ultrafiltration materials, but their practical applications are usually limited by brittleness. Recently, reversible compressibility has been realized in flexible nanostructures-based ceramic aerogels. However, these modified aerogels still show fast and brittle fracture under tension. Herein, we demonstrate achieving reversible stretch and crack insensitivity in a highly compressible ceramic aerogel through engineering its microstructure by using curly SiC-SiO

Background: Chronic diabetes accelerates vascular dysfunction often resulting in cardiomyopathy but underlying mechanisms remains unclear. Recent studies have shown that the deregulated unfolded protein response (UPR) dependent on highly conserved IRE1α-spliced X-box- binding protein (XBP1s) and the resulting endoplasmic reticulum stress (ER-Stress plays a crucial role in the occurrence and development of diabetic cardiomyopathy (DCM). In the present study, we determined whether targeting MAPK/ERK pathway using MEK inhibitor U0126 could ameliorate DCM by regulating IRE1α-XBP1s pathway.Method: Three groups of 8-week-old C57/BL6 mice were studied: one group received saline injection as control (n=8) and two groups were made diabetic by streptozotocin (STZ) (n=10 each). 18 weeks after STZ injection and stable hyperglycemia, one group had saline treatment while the second group was treated with U0126 (5mg/kg/day), 8 weeks later, all groups were sacrificed. Cardiac function/histopathological changes were determined by echocardiogram examination, Millar catheter system, hematoxylin-eosin staining and western blot analysis. H9c2 cardiomyocytes were employed for in vitro studies.Results: Echocardiographic, hemodynamic and histological data showed overt myocardial hypertrophy and worsened cardiac function in diabetic mice. Chronic diabetic milieu enhanced SUMOylation and impaired nuclear translocation of XBP1s. Intriguingly, U0126 treatment significantly ameliorated progression of DCM, and this protective effect was achieved through enriching XBP1s’ nuclear accumulation. Mechanistically, U0126 inhibited XBP1s’ phosphorylation on S348 and SUMOylation on K276 promoting XBP1s’ nuclear translocation. Collectively, these results identify that MEK inhibition restores XBP1s-dependent UPR and protects against diabetes-induced cardiac remodeling. Conclusion: The current study identifies previously unknown function of MEK/ERK pathway in regulation of ER-stress in DCM. U0126 could be a therapeutic target for the treatment of DCM.

Ceramic aerogels are attractive for their low density, high porosity, large surface area as well as various applications in areas of thermal insulation, catalysis, filtration, and lightweight structural materials. Conventional ceramic aerogels are usually assembled by oxides nanoparticles. Due to the inefficient neck-like connections between the nanoparticles and the volume shrinkage at elevated temperatures, ceramic aerogels fail easily caused by the brittleness and high-temperature structural collapse. To overcome these drawbacks, a class of resilient ceramic aerogels with highly porous architectures that are composed of one- or two-dimensional nanostructures has been prepared. Benefiting from the unique microstructures and/or the high-temperature stability of their building blocks, these aerogels exhibit reversible compressibility, high-temperature stability, thermal insulation, and various functions. In this review, we introduced the preparation methods, microstructures, mechanical properties, high-temperature stability, thermal insulation and various functions of these resilient ceramic aerogels. We have also discussed the relationships between their microstructures and properties, including mechanical properties and thermal insulation performance. Finally, perspectives for the further development of resilient ceramic aerogels are presented.

Lightweight electromagnetic (EM) wave absorbers made of ceramics have sparked tremendous interest for applications in EM wave interference protection at high temperatures. However, EM wave absorption by pure ceramics still faces huge challenges due to the lack of efficient EM wave attenuation modes. Inspired by the energy dissipation mechanism during fracture of lobster shells with a soft and stiff multilayered structure, we fabricate a high-performance EM wave absorption ceramic aerogel composed of an alternating multilayered wave transparent Si3N4 (N) layer and wave absorption SiC (C) layer by a simple restack method. The obtained N/C aerogel shows ultralow density (∼8 mg/cm3), broad effective absorption bandwidth (8.4 GHz), strong reflection loss (-45 dB) at room temperature, and excellent EM wave absorption performance at high temperatures up to 1000 °C. The attenuation of EM wave mainly results from a "reflection-absorption-zigzag reflection" process caused by the alternating multilayered structure. The superior absorption performance, especially at high temperatures, makes the N/C aerogel promising for next-generation wave absorption devices served in high-temperature environments.

General anesthesia is a powerful and indispensable tool to ensure the accomplishment of surgical procedures or clinical examinations. Sevoflurane as an inhalational anesthetic without unpleasant odor is commonly used in clinical practice, especially for pediatric surgery. However, the toxicity caused by sevoflurane has gained growing attention. Mitochondria play a key role in maintaining cellular metabolism and survival. To maintain the stability of mitochondrial homeostasis, they are constantly going through fusion and fission. Also, damaged mitochondria need to be degraded by autophagy, termed as mitophagy. Accumulating evidence proves that sevoflurane exposure in young age could lead to cell toxicity by triggering the mitochondrial pathway of apoptosis, inducing the abnormalities of mitochondrial dynamics and mitophagy. In the present review, we focus on the current understanding of mitochondrial apoptosis, dynamics and mitophagy in cell function, the implications for cell toxicity in response to sevoflurane, and their underlying potential mechanisms.

Turbidity of water significantly affect the system performance of underwater wireless optical communication (UWOC). In this letter, we proposed and experimentally demonstrated a loss-tolerant UWOC system using a compact high-power 520-nm laser diode (LD) and a highly sensitive silicon photomultiplier (SiPM). The LD is directly modulated by the on-off keying-non-return-to-zero (OOK-NRZ) data. A precise collimation system is designed in the transmitter so that the maximum beam divergence angle is fixed at 0.75 mrad. The performance of the proposed system is investigated over a 24-m underwater channel with different attenuation lengths (ALs) mimicking the different levels of water turbidity in coastal water. Experimental results show that the data rates of 20 Mbps, 40 Mbps, 80 Mbps and 100 Mbps can be achieved under 14.3 AL, 13.2 AL, 13.2 AL and 12.3 AL with bit error rates (BERs) lower than the forward error correction (FEC) limit.

Background In recent years, excellent results have suggested an association between the “brain-gut” axis and Alzheimer’s disease (AD) progression, yet the role of the “brain-gut” axis in AD pathogenesis still remains obscure. Herein, we provided a potential link between the central and peripheral neuroinflammatory disorders in AD progression. Methods The Morris water maze (MWM) test, immunohistochemistry, ELISA, ProcartaPlex Multiplex immunoassay, multiple LC-MS/MS methods, and the V3-V4 regions of 16S rRNA genes were applied to explore potential biomarkers. Results In Tg-APP/PS1 mice, gut dysbiosis and lipid metabolism were highly associated with AD-like neuroinflammation. The combination of inflammatory factors (IL-6 and INF-γ), phosphatidylcholines (PCs) and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD. Huanglian Jiedu decoction (HLJDD) suppressed gut dysbiosis and the associated Aβ accumulation, harnessed neuroinflammation and reversed cognitive impairment. Conclusion Together, our findings highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorder in AD progression. This integrated metabolomics approach showed its potential to understand the complex mechanisms of HLJDD in the treatment of AD.

Background and objectives Haemovigilance involves surveillance of the whole chain of blood transfusion with the aim of identifying adverse events and errors and improving outcomes for patients. The Chinese Haemovigilance Network, founded in August 2017, has witnessed a rapid development in the last three years. Materials and methods Based on the 1,022 cases in 2019, we analysed the adverse reactions (ARs) by blood component, clinical outcome severity and demography of recipients in an effort to publish the first annual Chinese haemovigilance report. Results The AR rate associated with blood transfusion in 2019 was 0·2% in China. Allergic reactions and FNHTR were the two most common adverse symptoms, accounting for 97·7% of the reports. Two-thirds of the TAD, AHTR and TACO and all of the HTR and DHTR resulted in hospitalization or prolongation of hospitalization. Plasma and AP were usually associated with allergic reaction (81·1%), whereas red cells more commonly cause FNHTR (68·8%) and all the AHTR, HTR, DSTR and DHTR. 84·1% of patients were aged 16 years or over, and the majority of the TAD, AHTR, TACO and HTR involved patients aged 60 and above. The ratio of serious adverse reactions (SARs) was 8·2%. Allergic reaction and FNHTR were top two (85·7%) SARs. The first case related to anti-D immunoglobulin was detected in a DHTR report. Conclusion This report provides the world's first overview of transfusion-related adverse reactions in China. This report is useful for better understanding transfusion risks in China.

Greater than 80% of all cancer cases are carcinomas, formed by the malignant transformation of epithelial cells. One of the key features of epithelial tumors is the presence of intercellular junctions, which link cells to one another and act as barriers to the penetration of molecules. This study assessed the expression of desmoglein-2, an epithelial junction protein, as a prognostic and diagnostic biomarker for ovarian cancer. Ovarian cancer sections were stained for DSG2 and signal intensity was correlated to cancer type and grade. DSG2 immunohistochemistry signals and mRNA levels were analyzed in chemo-resistant and chemo-sensitive cases. Ovarian cancer patient serum levels of shed DSG2 were correlated to disease-free and overall survival. Primary ovarian cancer cells were used to study DSG2 levels as they changed in response to cisplatin treatment. DSG2 expression was found to be positively correlated with cancer grade. Ovarian cancer patients with high serum levels of shed DSG2 fared significantly worse in both progression-free survival (median survival of 16 months vs. 26 months, p = .0023) and general survival (median survival of 37 months vs. undefined, p

Ultrasonic imaging is convenient and safe for cardiovascular disease diagnosis. Speckle tracking can obtain accurate myocardial movement data and provide important information for the diagnosis of cardiac function. Block matching method and optical flow method are the most commonly used speckle tracking methods. However, the accuracy of these methods cannot meet the needs of clinical application. Deep learning is applied to speckle tracking technology. Based on the correlation filters given to the deep convolution network, the migration learning method is introduced to obtain the feature mapping on the convolution layer on the pre-trained ImageNet VGG19 network. The feature mapping is used as the training data of correlation filters, and the tracking results obtained from convolution layers with different depths are filtered frame by frame, giving different weights to obtain the optimal tracking position within a certain search range. Then the correlation filter is updated to track the myocardial motion. The proposed deep learning based method has better accuracy for myocardial motion tracking, which indicates that the target tracking method based on convolutional neural network has potential advantages in this field.

Background: Thyroid nodules are a common clinical entity with high incidence. Ultrasound is often employed to detect and evaluate thyroid nodules. The development of an efficient automated method to detect thyroid nodules using ultrasound has the potential to reduce both physician workload and operator-dependence. Objective: To study the method of automatic detection of thyroid nodules based on deep learning using ultrasound, and to obtain the detection method with higher accuracy and better performance. Methods: A total of 1200 ultrasound images of thyroid nodules and 800 ultrasound thyroid images without nodule are collected. An improved faster R-CNN based detection method of thyroid nodule is proposed. Instead of using VGG16 as the backbone, ResNet is employed as the backbone for faster R-CNN. SVM, CNN and Faster-RCNN methods are used for thyroid nodule detection test. Precision, sensitivity, specificity and F1-score indicators are used to evaluate the detection performance of different methods. Results: The method based on deep learning is superior to that based on SVM. Faster R-CNN method and the improved method are better than CNN method. Compared with VGG16 as the backbone, RestNet101 backbone based faster R-CNN method achieves better thyroid detection effect. From the accuracy index, the proposed method is 0.084, 0.032 and 0.019 higher than SVM, CNN and faster R-CNN, respectively. Similar results can be seen in precision, sensitivity, specificity and F1-Score indicators. Conclusion: The proposed method of deep learning achieves the best performance values with the highest true positive and true negative detection compared to other methods and performs best in the detection of thyroid nodules.

In this Letter, a two-dimensional (2D) beam steering on silicon nitride (SiNx) nanophotonic phased arrays from visible to near-infrared wavelengths is reported for the first time, to the best of our knowledge. In order to implement beam steering along the transverse direction for one-dimensional waveguide surface grating arrays, wavelengths from 650 to 980 nm provided by the supercontinuum laser are used to excite the phased array. Then the beams are parallel radiated with steering angles in a sequence of 26.84° to − 16.54 ∘ along the transverse direction, and a continuous line in the far field consisting of parallel emitted spots is produced with a total view angle of 43.38°. Moreover, this continuous far-field line is steered along the longitudinal direction with massive wavelengths simultaneously tuned by phase shifts from − π / 2 to over + π / 2 . This method with massive parallel wavelengths emitted paves a new way for 2D steering on SiNx nanophotonic phased arrays.

Our goal is to overcome treatment resistance in ovarian cancer patients which occurs in most cases after an initial positive response to chemotherapy. A central resistance mechanism is the maintenance of desmoglein-2 (DSG2) positive tight junctions between malignant cells that prevents drug penetration into the tumor. We have generated JO4, a recombinant protein that binds to DSG2 resulting in the transient opening of junctions in epithelial tumors. Here we present studies toward the clinical translation of c-JO4 in combination with PEGylated liposomal doxorubicin/Doxil for ovarian cancer therapy. A manufacturing process for cGMP compliant production of JO4 was developed resulting in c-JO4. GLP toxicology studies using material from this process in DSG2 transgenic mice and cynomolgus macaques showed no treatment-related toxicities after intravenous injection at doses reaching 24 mg/kg. Multiple cycles of intravenous c-JO4 plus Doxil (four cycles, 4 weeks apart, simulating the treatment regimen in the clinical trial) elicited antibodies against c-JO4 that increased with each cycle and were accompanied by elevation of pro-inflammatory cytokines IL-6 and TNFα. Pretreatment with steroids and cyclophosphamide reduced anti-c-JO4 antibody response and blunted cytokine release. Our data indicate acceptable safety of our new treatment approach if immune reactions are monitored and counteracted with appropriate immune suppression.

We report a simple concept to implement a single-wavelength beam steering based on a liquid-cladded one-dimensional (1D) optical phased array (OPA). The beam steering was realized by modifying the waveguide mode effective index through replacing the liquid upper claddings. A prototype of a 32-channel liquid-cladded OPA was fabricated and characterized. Owing to the high refractive index range of liquids ( > 0.625 ), a maximum steering angle of > 10 ∘ was achieved with the liquid range from 1.0 to 1.63 at a wavelength of 940 nm. Moreover, the liquid-cladded OPA reveals a quasi-continuous beam steering range of > 29 ∘ by combining the liquid cladding tuning and discrete wavelength tuning of λ = 785 n m , 852 nm, and 940 nm. Further integration with optofluidic systems offers the OPA potential for low power consumption and all-fluidic beam steering operating at a single wavelength.

Big data has been prominent in studying aging and older people’s health. It has promoted modeling and analyses in biological and geriatric research (like cellular senescence), developed health management platforms, and supported decision-making in public healthcare and social security. However, current studies are still limited within a single subject, rather than flourished as interdisciplinary research in the context of big data. The research perspectives have not changed, nor has big data brought itself out of the role as a modeling tool. When embedding big data as a data product, analysis tool, and resolution service into different spatial, temporal, and organizational scales of aging processes, it would present as a connection, integration, and interaction simultaneously in conducting interdisciplinary research. Therefore, this paper attempts to propose an ecological framework for big data based on aging and older people’s health research. Following the scoping process of PRISMA, 35 studies were reviewed to validate our ecological framework. Although restricted by issues like digital divides and privacy security, we encourage researchers to capture various elements and their interactions in the human-environment system from a macro and dynamic perspective rather than simply pursuing accuracy.

In this paper, an effective method of underwater coherent optical wireless communication (UCOWC) with a simplified detection scheme is proposed. The proof-of-concept experiments with M-ary PSK have been conducted with a common laser used for the signal source and local oscillator (LO). The BER performance has been evaluated at different underwater channel attenuations and the maximum achievable attenuation length (AL) with a BER below the forward error correction (FEC) limit of 3.8×10−3 is investigated. The tested system offers data rates of 500 Mbps, 1 Gbps, and 1.5 Gbps with the BPSK, QPSK and 8PSK modulated signals, respectively. The corresponding maximum achievable attenuation lengths are measured as 13.4 AL 12.5 AL, and 10.7 AL. In addition, the performance degradation of the practical system with separate free running lasers for the signal and LO is also estimated. To the best of our knowledge, the UCOWC system is proposed and experimentally studied for the first time. This work provides a simple and effective approach to take advantages of coherent detection in underwater wireless optical communication, opening a promising path toward the development of practical UCOWC with next-generation underwater data transmission requirements on the capacity and transmission distance.

An innovative architecture is presented that combines energy-dense and power-dense battery packs through a supercapacitor that provides capacitive coupling and a low-power DC-DC converter that provides energy balancing. A sizing algorithm is developed to optimize the design of such systems for plug-in hybrid and battery electric vehicles (PHEVs and BEVs). The proposed composite architecture extends vehicle range and battery lifetime by fully utilizing the capabilities of energy-dense and power-dense battery chemistries. A power-dense battery is coupled to an energy-dense battery using a small supercapacitor module that naturally distributes the system current between the two packs, requiring no additional contactors or full-power processing DC-DC converters. The proposed algorithm provides a tool for designing the composite architecture to achieve maximum weight reduction under given conditions for both ideal and practical scenarios. A design example is provided based on a PHEV with 68-mile range using the US06 drive cycle. The design achieved a 42% weight reduction when compared to a similar design with a conventional single chemistry battery system. Experimental results of a 1.5 kW, 0.2 kWh small-scale prototype with 25 Ah NMC and 2.9 Ah LTO battery cells and a 30 F supercapacitor verify the natural distribution of system current between the energy-dense and power-dense packs.

Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by the complex interaction of multiple mechanisms. Recent studies examining the effect of high-fat diet (HFD) on the AD phenotype have demonstrated a significant influence on both inflammation and cognition. However, different studies on the effect of high-fat diet on AD pathology have reported conflicting conclusions. To explore the involvement of HFD in AD, we investigated phenotypic and metabolic changes in an AD mouse model in response to HFD. The results indicated there was no significant effect on Aβ levels or contextual memory due to HFD treatment. Of note, HFD did moderate neuroinflammation, despite spurring inflammation and increasing cholesterol levels in the periphery. In addition, diet affected gut microbiota symbiosis, altering the production of bacterial metabolites. HFD created a favorable microenvironment for bile acid alteration and arachidonic acid metabolism in APP/PS1 mice, which may be related to the observed improvement in LXR/PPAR expression. Our previous research demonstrated that Huanglian Jiedu decoction (HLJDD) significantly ameliorated impaired learning and memory. Furthermore, HLJDD may globally suppress inflammation and lipid accumulation to relieve cognitive impairment after HFD intervention. It was difficult to define the effect of HFD on AD progression because the results were influenced by confounding factors and biases. Although there was still obvious damage in AD mice treated with HFD, there was no deterioration and there was even a slight remission of neuroinflammation. Moreover, HLJDD represents a potential AD drug based on its anti-inflammatory and lipid-lowering effects.

Considering a demand response (DR) based social welfare maximization model, a complementarity problem based on the Karush-Kuhn-Tuker condition is described, which is a non-dual method for determining real-time price for smart grids. The Lagrange multiplier in the dual method, which is used to determine the basic electricity price, is applied in the model. The proposed method computes the optimal electricity consumption, price and production. According to the electricity price, users can arrange their electricity equipment reasonably to reduce the consumption pressure at peak time. The model aims to encourage users to actively participate in the DR and realize peak cutting and valley filling. In addition, the model considers different utility functions representing three types of users. Finally, a Jacobian smoothing version of Newton method is used to solve the model. Statistical simulations of the model validate the rationality and feasibility of the proposed method.

With the prevailing energy challenges and the rapid development of aerospace engineering, high-performance thermal insulators with various functions are attracting more and more attention. Ceramic aerogels are promising candidates for thermal insulators to be applied in harsh environments because of their low thermal conductivity and simultaneously excellent thermal and chemical stabilities. In general, the effective properties of this class of materials depend on both their microstructures and the intrinsic properties of their building blocks. Herein, to enrich the family and broaden the application fields of this class of materials, we prepared ultralight α-Si3N4 nanobelt aerogels (NBAs) with tunable densities ranging from 1.8 to 9.6 mg cm-3. The α-Si3N4 NBA realized resilient compressibility (with a recoverable strain of 40-80%), fire resistance (1200 °C butane blow torch), thermal insulation (0.029 W m-1 K-1), and electronic wave transparency (a dielectric constant of 1-1.04 and a dielectric loss of 0.001-0.004) in one material, which makes it a promising candidate for mechanical energy dissipative, fire-resistant, and electronic wave-transparent thermal insulator to be applied in extreme conditions. The successful preparation of such resilient and multifunctional α-Si3N4 NBAs will open up a new world for the development and widespread applications of ceramic aerogels.

The real-time pricing mechanism of smart grid based on demand response is an effective means to adjust the balance between energy supply and demand, whose implementation will impact the user's electricity consumption behaviour, the operation, and management in the future power systems. In this paper, we propose a complementarity algorithm to solve the real-time pricing of smart grid. The Karush–Kuhn–Tucker condition is considered in the social welfare maximisation model incorporating load uncertainty to transforming the model into a system of nonsmooth equations with Lagrangian multipliers, i.e., the shadow prices. The shadow price is used to determine the basic price of electricity. The system of nonsmooth equations is a complementarity problem, which enables us to study the existence and uniqueness of the equilibrium price and to design an online distributed algorithm to achieve the equilibrium between energy supply and demand. The proposed method is implemented in a simulation system composed of an energy provider and 100 users. Simulations results show that the proposed algorithm can motivate the users’ enthusiasm to participate in the demand side management and shift the peak loading. Furthermore, the proposed algorithm can improve the supply shortage. When compared with an online distributed algorithm based on the dual optimisation method, the proposed algorithm has a significantly lower running time and more accurate Lagrangian multipliers.

Unmineable coal accounts for over 90% of the world’s fossil fuel resources. Fortunately, many coal seams contain indigenous microorganisms capable of utilizing the coal as a carbon source to produce secondary biogenic coalbed natural gas. However, coal bioavailability has been shown to be a significant factor that limits the extent of bioconversion. In this study, we have analyzed the rate and yield of the biogas production and assessed the gas potential, carbon balance, stable carbon isotopes, microbial communities, and microbial pathways changes resulting from the hydrogen peroxide pretreatment with the Wyoming’s Powder River Basin subbituminous coal. The results showed that coal pretreated with hydrogen peroxide can significantly enhance the bioavailability of coal for enhancing the biogas production, with a peak yield of 552.6 μmol/g coal (437.1 Scf/ton coal) at the day 184. The stable carbon isotopic analysis indicated that the δ13C values of the methane and carbon dioxide were much less negative than the published field data. This suggested that the enrichment or depletion of the precursor 13C could contribute to the shift of the carbon isotopic composition in the subsequence processes. Therefore, the data should be used with cautions for interpreting genesis of the thermogenic/biogenic methane and the methanogenic pathways. The methanogenic pathways were also investigated with re-fed experiment and microbial community analysis. The results indicated that the hydrogenotrophic pathway was not active in the original inoculum became activated after the gas production. The microbial community analysis demonstrated that the obligate hydrogenotrophic methanobacterium was the most dominant methanogens in the microcosms after the gas production. This suggested that the chemical treatment of coal has impacts on the microbial structure during the subsequent methane production phase.

Current thalassemia gene therapy protocols require the collection of hematopoietic stem/progenitor cells (HSPCs), in vitro culture, lentivirus vector transduction, and retransplantation into myeloablated patients. Because of cost and technical complexity, it is unlikely that such protocols will be applicable in developing countries, where the greatest demand for a β-thalassemia therapy lies. We have developed a simple in vivo HSPC gene therapy approach that involves HSPC mobilization and an intravenous injection of integrating HDAd5/35++ vectors. Transduced HSPCs homed back to the bone marrow, where they persisted long-term. HDAd5/35++ vectors for in vivo gene therapy of thalassemia had a unique capsid that targeted primitive HSPCs through human CD46, a relatively safe SB100X transposase–based integration machinery, a micro-LCR–driven γ-globin gene, and an MGMT(P140K) system that allowed for increasing the therapeutic effect by short-term treatment with low-dose O(6)-benzylguanine plus bis-chloroethylnitrosourea. We showed in “healthy” human CD46–transgenic mice and in a mouse model of thalassemia intermedia that our in vivo approach resulted in stable γ-globin expression in the majority of circulating red blood cells. The high marking frequency was maintained in secondary recipients. In the thalassemia model, a near-complete phenotypic correction was achieved. The treatment was well tolerated. This cost-efficient and “portable” approach could permit a broader clinical application of thalassemia gene therapy.

“Shanghuo” (“excessive internal heat”) is caused by exuberant endogenous fire, which does not have a comprehensive and systematic traditional Chinese medicine theory. In previous study, we had evaluated the therapeutic effect of Huanglian Jiedu Decoction (HLJDD) (granule) on patients with “Shanghuo”, however, the specific mechanism was not clear, which need further exploration. To explain its intervention mechanism, we select 57 patients with oral diseases caused by “Shanghuo” and 20 health volunteers to divide into oral disease group, HLJDD intervention group and healthy control group. Firstly, biochemical indicators before and after HLJDD intervention are detected, such as inflammatory factors, oxidative stress factors and energy metabolism factors. The results exhibit that HLJDD significantly decreases indicators succinic acid (p < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid (p < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase (p < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone (p < 0.01); lactic acid, IL-4, IL-10 (p < 0.05) significantly increase after HLJDD intervention. In addition, we adopt multi-omics analysis approach to investigate the potential biomarkers. Nontargeted metabolomics demonstrate that the levels of 7 differential metabolites approach that in the healthy control group after HLJDD intervention, which are correlated with histidine metabolism, beta-alanine metabolism and sphingolipid metabolism through metabolic pathway analysis. Targeted lipidomics results and receiver operating characteristic curve analysis show that 13 differential lipids are identified in the three groups mainly focuse on lysophosphatidylcholines, lysophosphatidylethanolamines. Finally, the network associations of those differential biomarkers reveal the regulation of adenosine triphosphate and tricarboxylic acid cycle play essential role in the therapeutic effect mechanism of HLJDD in “Shanghuo”. The study has laid the foundation for further revealing the mechanism and finding clinical biomarkers related to “Shanghuo”.

Sewage and fecal pollution cause antibiotic resistance genes (ARGs) pollution in urban lagoons. Seasonality also affects ARG dynamics. However, knowledge of factors controlling ARG community assembly across seasons is still limited. Here, we revealed the seasonal variation of ARGs and depict the underlying assembly processes and drivers via high-throughput quantitative PCR in an urban lagoon, China. A higher richness and abundance of ARGs were observed in summer and winter compared to spring and fall (Kruskal-Wallis test, P 0.05). Both ARG and prokaryotic communities were mainly governed by stochastic processes, however, these processes drove ARGs and prokaryotes differently across seasons. Stochastic processes played a more dominant role in shaping ARG communities in summer (average stochasticity: 83%) and winter (75%), resulting in a stable antibiotic resistome. However, no such seasonal pattern of stochastic processes was determined for prokaryotes, indicating a decoupling of the assembly process of ARGs and prokaryotes. Moreover, fecal microorganisms (e.g., Bacteroidetes and Faecalibacterium) mediated the stochastic processes of ARG profiles, via enhancement of prokaryotic biomass and mobile genetic element abundances. The tnpA-07 transposase was the key for the horizontal gene transfer. These findings will enhance our understanding of how fecal pollution shapes ARG community assembly in urban lagoons.

In this work, beam steering angle of 65° is achieved on a 32-channel antennas phased array. We demonstrate a wide range of beam steering in visible band with a supercontinuum laser for the first time.

We demonstrate large scale optical waveguide grating antennas with uniform emission operating from 1450nm to 1650nm. By tuning the laser wavelength, the beam steering angle of 30°was achieved.

We experimentally measured the radiation of optical phased arrays fabricated on SOI waveguide platform. By tuning the input laser wavelength, we realized one-dimension beam steering and observed standing-wave patterns in the waveguide antennas.

Excessive utilization of chemical fertilizers (CF) is not a sustainable agricultural development strategy due to adverse effects on soil health. In contrast, a combination of organic and mineral fertilizers has a positive effect on both soil health and productivity. Chinese medicinal herbal residues (CMHR) is the plant material wastes remaining after drug extraction but has not been extensively used as fertilizer. We evaluated application of CMHR to maize fields over 3 consecutive growing seasons in the presence and absence of standard CF to assess improvements in soil fertility, maize yields and sustainable development. CMHR fertilization increased soil organic matter and total N and K when mixed with chemical fertilizer at 50 and 75% the standard application rate. Soil organic matter increased by 27.0-51.4% and available -N, -P and -K levels and grain yields as well as N and P use efficiency in the presence of CMHR mixes were similar to levels obtained with chemical fertilizer only. These increases in production were due to increased leaf areas, photosynthetic rates, grain number and 1000-grain weights. The addition of CMHR to fields posed a slightly risk of toxic-metal pollution. Overall, we found that (1) CMHR can be used as an effective organic fertilizer and replace up to 50% of the amount of chemical fertilizer normally applied to fields without hampering maize grain yields and (2) CMHR application to agricultural fields is an effective recycling strategy and nutrient management practice to improve soil fertility under CF usage reduction.

To determine the incidence of acute cardiac injury (ACI), the factors associated with ACI and the in-hospital mortality in patients with COVID-19, especially in severe patients. All consecutive in-patients with laboratory-confirmed COVID-19 from Tongji Hospital in Wuhan during February 1 and March 29, 2020 were included. The demographic, clinical characteristics, laboratory, radiological and treatment data were collected. Univariate and Firth logistic regression analyses were used to identify factors associated with ACI and in-hospital mortality, and Kaplan–Meier method was used to estimate cumulative in-hospital mortality. Among 1031 patients included, 215 (20.7%) had ACI and 501 (48.6%) were severe cases. Overall, 165 patients died; all were from the severe group, and 131 (79.39%) had ACI. ACI (OR = 2.34, P = 0.009), male gender (OR = 2.58, P = 0.001), oximeter oxygen saturation (OR = 0.90, P P P P = 0.016), N-terminal pro brain natriuretic peptide (NT-proBNP) (OR = 2.94, P = 0.001) were independent risk factors for the in-hospital mortality in severe patients. The mortality was significantly increased among severe patients with elevated hs-CRP, IL-6, hs-cTnI, and/or NT-proBNP. Moreover, the mortality was significantly higher in patients with elevation of both hs-cTnI and NT proBNP than in those with elevation of either of them. ACI develops in a substantial proportion of patients with COVID-19, and is associated with the disease severity and in-hospital mortality. A combination of hs-cTnI and NT-proBNP is valuable in predicting the mortality.

Alleviating range anxiety for electric vehicles (i.e., whether such vehicles can be relied upon to travel long distances in a timely manner) is critical for sustainable transportation. Extremely fast charging (XFC), whereby electric vehicles (EV) can be quickly recharged in the time frame it takes to refuel an internal combustion engine, has been proposed to alleviate this concern. A critical component of these chargers is the efficient and proper operation of power converters that convert AC to DC power and otherwise regulate power delivery to vehicles. These converters rely on the integrity of sensor and actuation signals. In this work the operation of state-of-the art XFC converters is assessed in adversarial conditions, specifically against Intentional Electromagnetic Interference Attacks (IEMI). The targeted system is analyzed with the goal of determining possible weak points for IEMI, viz. voltage and current sensor outputs and gate control signals. This work demonstrates that, with relatively low power levels, an adversary is able to manipulate the voltage and current sensor outputs necessary to ensure the proper operation of the converters. Furthermore, in the first attack of its kind, it is shown that the gate signal that controls the converter switches can be manipulated, to catastrophic effect; i.e., it is possible for an attacker to control the switching state of individual transistors to cause irreparable damage to the converter and associated systems. Finally, a discussion of countermeasures for hardware designers to mitigate IEMI-based attacks is provided., Accepted by IEEE S&P Workshop on the Internet of Safe Things 2020

This paper presents a grid-frequency to high-frequency AC-AC converter and its control scheme for wireless charging applications. The proposed AC-AC converter utilizes a T-type converter to process the soft DC-link generated by a 3-φ unfolder. A control strategy for the T-type converter to perform both power factor correction and output voltage or current control simultaneously is presented in this paper. The expressions for duty ratios of the T-type converter are derived using the fundamental harmonic analysis method. Simulation results for a 100 kW system driving a series-series compensated wireless charging topology are presented to validate the control method. Hardware results of a 1 kW scaled-down prototype with less than 2% grid current THD using feed-forward control are presented to demonstrate the applicability of the proposed system.

Nonamyloidogenic processing of amyloid precursor protein (APP) by augmenting ADAM10 is a promising therapeutic strategy for Alzheimer’s disease (AD). Therefore identification of molecular pathways that regulate ADAM10 expression is crucial. Autophagy is strongly dysregulated in AD, and TFEB was recently shown to be a master regulator of autophagy-lysosome pathway (ALP). Here, we report that TFEB expression in HeLa cells increased ADAM10 mature form by 72% (p

Under the complex situation of Manned/Unmanned Aerial Vehicles(MAV/UAV) mixed operation, it is difficult to design proper control strategy and parameter for UAV collaborative actions. To solve this problem, a UAV reinforcement learning algorithm based on game theory is proposed. Considering the characteristics of multi-Vehicles collaboration, the merits of MAXQ hierarchical reinforcement learning and multi-agent are combined, and propose a UAV coordination method based on MAXQ multi-agent hierarchical reinforcement learning, in order to improve the UAV adaptation and self-coordination ability under complex situation of mixed operation. It is demonstrated by the simulation results that the proposed hierarchical reinforcement learning algorithm performs better and its learning rate and efficiency are higher than the traditional hierarchical reinforcement learning.

Constructed wetlands (CWLs) are widely used for water environment protection. In some cases, CWL animals can help improve CWL treatment efficiency and contribute to CWL maintenance and management. However, while plants, microorganisms, and substrates in CWLs have received much attention, animals have been largely ignored. Therefore, the aims of this review are to determine the roles wetland animals play in the water environmental protection of CWLs. This study introduced species of wetland animals and the main factors that can affect their survival. The way in which CWL animals affect pollutants was discussed in detail from four perspectives: adsorption and bioaccumulation, bioturbation, and the influence of CWL animals on plants and microorganisms. The characteristics of CWL animals that can be used for biological monitoring are summarized, and the use of CWLs for the protection of wetland biodiversity is also discussed. Finally, some prospects are proposed for future research. This study will help researchers better understand the role of CWL animals in CWLs and encourage researchers to focus on studies of wetland animals.

Ceramic aerogels are promising lightweight and high-efficient thermal insulators for applications in buildings, industry, and aerospace vehicles but are usually limited by their brittleness and structural collapse at high temperatures. In recent years, fabricating nanostructure-based ultralight materials has been proved to be an effective way to realize the resilience of ceramic aerogels. However, the randomly distributed macroscale pores in these architectures usually lead to low stiffness and reduced thermal insulation performance. Here, to overcome these obstacles, a SiC@SiO2 nanowire aerogel with a nanowire-assembled anisotropic and hierarchical microstructure was prepared by using directional freeze casting and subsequent heat treatment. The aerogel exhibits an ultralow thermal conductivity of ~14 mW/m·K, an exceptional high stiffness (a specific modulus of ~24.7 kN·m/kg), and excellent thermal and chemical stabilities even under heating at 1200°C by a butane blow torch, which makes it an ideal thermally superinsulating material for applications under extreme conditions.

Background: Coronary artery disease (CAD) is a type of cardiovascular disease that greatly hurts the health of human beings. Diabetic status is one of the largest clinical factors affecting CAD-associated gene expression changes. Most of the studies focus on diabetic patients, whereas few have been done for nondiabetic patients. Since the pathophysiological processes may vary among these patients, we cannot simply follow the standard based on the data from diabetic patients. Therefore, the prognostic and predictive diagnostic biomarkers for CAD in nondiabetic patient need to be fully recognized. Materials/Methods: To screen out candidate genes associated with CAD in nondiabetic patients, weighted gene coexpression network analysis (WGCNA) was constructed to conduct an analysis of microarray expression profiling in patients with CAD. First, the microarray data GSE20680 and GSE20681 were downloaded from NCBI. We constructed coexpression modules via WGCNA after excluding the diabetic patients. As a result, 16 coexpression modules were screened out, including 1225 differentially expressed genes (DEGs) that were obtained from 152 patients (luminal stenosis ≥ 50% in at least one major vessel) and 170 patients (stenosis of < 50%). Subsequently, a Pearson’s correlation analysis was conducted between the modules and clinical traits. Then, a functional enrichment analysis and protein-protein interaction (PPI) analysis was conducted to reveal hub genes. Last, we validated the hub genes with peripheral blood samples in an independent patient cohort using RT-qPCR. Results: The results showed that the midnight blue module and yellow module played vital roles in the pathogenesis of CAD in nondiabetic patients. Additionally, CD40, F11R, TNRC18, and CAMK2G were screened out and validated using enzyme-linked immunosorbent assay (ELISA) in an independent patient cohort and immunohistochemical (IHC) staining in an atherosclerosis mouse model. Conclusions: Our findings demonstrate that hub genes, CD40, F11R, TNRC18, and CAMK2G, are surrogate diagnostic biomarkers and/or therapeutic targets for CAD in nondiabetic patients and require deeper validation. Keywords: coronary artery disease (CAD); nondiabetic patients; weighted gene coexpression network analysis (WGCNA); function enrichment analysis; biomarkers.

With the booming of modern information technology, electromagnetic wave (EMW) absorption materials are playing more and more crucial roles in applications ranging from wearable smart electronics to national defense security. However, the application of present EMW absorption materials is severely hindered by their drawbacks, such as narrow absorption bandwidth and low absorption intensity. In this work, a series of highly porous and well-interconnected SiC@C nanowire foams (SCNFs) are rationally designed to exhibit modified impedance match and multiscale EMW energy dissipation mechanisms. The SCNF with a density of 108 mg cm

Huang-Lian-Jie-Du Decoction (HLJDD), traditional Chinese medicine (TCM), is proven to have ameliorative effects on learning and memory deficits of Alzheimer’s disease (AD). The current study aims to reveal the underlying mechanism of HLJDD in the treatment of AD by simultaneous determination on the regulation of HLJDD on oxidative stress, neurotransmitters, and AMPK-SIRT1 pathway in AD. AD model rat was successfully established by injection of D-galactose and Aβ25-35-ibotenic acid. Morris Water Maze (MWM) test was used to evaluate the success of AD modelling. On this basis, an advanced technique with UPLC-QqQ MS/MS was built up and applied to determine the levels of 8 neurotransmitters in rat plasma. Significant alternation in methionine, glutamine, and tryptophan was observed in AD rats’ plasma after the administration of HLJDD, relative to the model group. Meanwhile, HLJDD could upregulate the levels of SOD, GSH-Px, AMPK, and SIRT1 and downregulate the content of MDA in the peripheral system of the AD rats. The underlying therapeutic mechanism of HLJDD for the treatment of AD was associated with alleviating oxidation stress, inflammation, neurotransmitters, and energy metabolism. These data provide solid foundation for the potential use of HLJDD to treat AD.

Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiovascular disease that is a serious threat to human life. However, the specific diagnostic biomarkers have not been fully clarified and candidate regulatory targets for IPAH have not been identified. The aim of this study was to explore the potential diagnostic biomarkers and possible regulatory targets of IPAH. We performed a weighted gene coexpression network analysis and calculated module-trait correlations based on a public microarray data set (GSE703) and six modules were found to be related to IPAH. Two modules which have the strongest correlation with IPAH were further analyzed and the top 10 hub genes in the two modules were identified. Furthermore, we validated the data by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent sample set originated from our study center. Overall, the qRT-PCR results were consistent with most of the results of the microarray analysis. Intriguingly, the highest change was found for YWHAB, a gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-containing proteins. Thus, YWHAB was subsequently selected for validation. In congruent with the gene expression analysis, plasma 14-3-3β concentrations were significantly increased in patients with IPAH compared with healthy controls, and 14-3-3β expression was also positively correlated with mean pulmonary artery pressure ( R 2 = 0.8783; p

To achieve the flow mechanism during the closure of the guide vanes in a pump-turbine in pump mode, a three-dimensional (3-D) incompressible simulation using the shear stress transition (SST) k-ω turbulence model was performed. The dynamic mesh method was adopted to simulate the closing process of the guide vanes. Based on the validation of the steady experiments, the variation in performance characteristics (head, discharge, and torque), pressure, and velocity was presented, which shows dynamic instability at the end of the guide vanes closing process. Numerical results confirm that the dynamic instabilities at the end of the closing process originated from severe fluctuations that occurred in the guide and stay vanes. Detailed analyses of flow characteristics reveal that severe fluctuations occur due to vortices in the stay vanes, and a high-pressure circular ring in the vaneless space and a low-pressure circular ring between the guide vanes outlet and stay vanes inlet were identified. During the closing process of the guide vanes opening, the vortices appear in several passages initially, and then increasingly spread to all the passages. The position and rotating direction of the vortices vary with time. Using the Q-criterion method, the composition and evolution of vortex structures in stay vanes were identified. These structures comprise streamwise vortices, horseshoe-shaped vortices, and spanwise vortices, which lead to severe pressure fluctuations.

Wetlands play an important role in sustaining ecosystems on the earth, which regulate water resources, adjust local climate and produce food for human beings, etc. However, wetlands are facing huge challenges due to human activities and other natural evolution, such as area shrinkage, function weakening and biodiversity decrease, and so on, therefore, some wetlands need to be urgently restored. In this study, the main technology components of close-to-natural restoration of wetlands were summarized. The ecological water requirement and water resource allocation can be optimized for the water balance between social, economy and ecology, which is a key prerequisite for maintaining wetland ecosystem. The pollution of wetland sediments and soils can be assessed by various indicators to provide the scientific basis for natural restoration of wetland base, and suitable strategies should be taken according to the actual conditions of wetland bases. The hydrological connectivity in wetlands and with related water system can be numerically simulated to make the optimal plan for improvement of hydrological connectivity. The ecological restoration of wetlands with the synergetic function of plants, animals and microorganisms was summarized, to improve the quality of wetland water environment and maintain the ecosystem stability. Based on the wetland close-to-natural restoration strategies, a brief ecological restoration plan for a typical wetland, Zaozhadian Wetland, near Xiong'an New Area in the north China was proposed from water resource guarantee, base pollution management, hydrological connectivity improvement and biological restoration. The close-to-natural restoration shows more effective, sustainable and long-lasting and thus a practical prospect.

Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4+FOXP3+). Preincubation of pan T-cells with aPC prior to transplantation increases the frequency of Tregs and protects from GvHD. Preincubation of human T-cells (HLA-DR4−CD4+) with aPC prior to transplantation into humanized (NSG-AB°DR4) mice ameliorates graft-vs.-host disease. The protective effect of aPC on GvHD does not compromise the graft vs. leukaemia effect in two independent tumor cell models. Ex vivo preincubation of T-cells with aPC, aPC-based therapies, or targeting PAR2/PAR3 on T-cells may provide a safe and effective approach to mitigate GvHD., Graft-vs.-host disease is a complication of allogenic hematopoietic stem cell transplantation, and is associated with endothelial dysfunction. Here the authors show that activated protein C signals via PAR2/PAR3 to expand Treg cells, mitigating the disease in mice.

Performance characteristics in pump mode of pump-turbines are vital for the safe and effective operation of pumped storage power plants. They are resultant of Euler head (power input) and hydraulic losses (power dissipation). In this paper, 3-D steady simulations were performed under 13mm, 19mm and 25mm guide vane openings (GVOs). Three groups of operating points under the three GVOs were chosen based on experimental validation to investigate the influence of guide vane setting on flow patterns upstream and downstream. Analysed results show that, the guide vane setting will obviously change the flow pattern downstream, which in turn influences the flow upstream. It shows a strong effect on hydraulic losses in guide and stay vanes. In addition, at the large part load conditions, the change of GVO will increase the relative flow angle at the runner outlet. As a consequence, it decreases the Euler head. However, at other operating conditions, it only has a little influence on Euler head. Flow patterns in pump mode are very dependent on the GVO and discharge.

Current gene therapy or genome editing studies for hemoglobinopathies require highly sophisticated medical facilities to perform hematopoietic stem cell collections / selections and genetic modifications. In addition, patients receive high-dose chemotherapy to facilitate engraftment of gene-modified cells. Thus, current gene therapy protocols will not be accessible to most patients suffering from hemoglobinopathies. Here we describe a highly portable and scalable approach using in vivo hematopoietic stem cell (HSC) gene therapy to potentially overcome these limitations. The central idea of our in vivo HSC gene therapy approach is to mobilize HSCs from the bone marrow, and while they circulate at high numbers in the periphery, transduce them with an intravenously injected HSC-tropic, helper-dependent adenovirus HDAd5/35++ gene transfer vector system. Transduced cells return to the bone marrow where they persist long-term. Transgene integration is either achieved by a Sleeping Beauty transposase (SB100x) in a random pattern or by homology-directed-repair into a safe genomic harbor site. Currently, an in vivo selection system (involving the mgmtP140K gene/low-dose O6BG/BCNU) is employed to achieve 80-100% marking levels in peripheral blood cells. We demonstrated safety and efficacy of our approach in mouse models for thalassemia intermedia, Sickle Cell Disease, and hemophilia A, where we achieved a phenotypic correction. We now present data in 3 rhesus macaques. We show that treatment with G-CSF/AMD3100 resulted in efficient HSC mobilization into the blood circulation and subsequent intravenous injection of the HDAd5/35++ vector system (total 1-3 x1012 vp/kg, in two doses) was well tolerated. The longest follow up thus far is 24 weeks after in vivo HSC transduction with a human-gamma-globin expressing HDAd5/35++ vector. After in vivo selection with O6BG plus low dose (10 to 20 mg/m2) of BCNU, a dose that is up to 100-fold lower than what is used for autologous transplantation protocols, gamma-globin marking in peripheral red blood cells rose to ~90% and was stable for the duration of the study (see Figure). gamma-globin levels in red blood cells were ~18% of adult alpha1-globin (by HPLC). No abnormalities in genome and transcriptome analyses of animal #1 were found at the time of scheduled necropsy. We show that a new prophylaxis regimen (dexamethasone, IL-6R, IL-1bR antagonists, saline bolus IV) was able to mitigate all side effects associated with intravenous HDAd5/35++ vector administration. Analysis of day 3 bone marrow showed 30% transduced HSCs. Vector DNA biodistribution studies demonstrated very low or absent transduction of most tissues (including testes and CNS). Analysis of bone marrow showed efficient, preferential HSC transduction and re-homing of transduced CD34+/CD90+ cells to the bone marrow. At week 4, about 5% of progenitor colony-forming cells demonstrated stable transduction with integrated vector, and this frequency increased after starting the in vivo selection. The level of human mgmtP140K mRNA expression in PBMCs also increased after in vivo selection. In summary: Using a new and optimized prophylaxis regimen intravenous delivery of HDAd5/35++ was very well tolerated without any cytokine activation. We saw efficient transduction of HSCs and efficient in vivo selection of transduced progenitors with low dose O6BG/BCNU. This is the first proof-of-concept study that in vivo HSC gene therapy could be feasible in humans without the need of high-dose chemotherapy conditioning and without the need for highly specialized medical facilities. This approach would provide a major advance for the gene therapy and genome editing field and allow the necessary portability and accessibility to reach patients in places with limited medical resources. Figure 1 Disclosures Radtke: Forty Seven INC: Consultancy. Kiem:Umoja: Membership on an entity's Board of Directors or advisory committees; Rocket Pharma: Membership on an entity's Board of Directors or advisory committees; Vor Biopharma: Membership on an entity's Board of Directors or advisory committees; Enochian: Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy; Magenta Therapeutics: Consultancy; Homology Medicines: Membership on an entity's Board of Directors or advisory committees. Lieber:Ensoma, Inc: Consultancy, Research Funding.

We report on a passively mode-locked oscillator based on an erbium-doped dual concentric core fiber combining high normal dispersion and large mode area. This large normal dispersion laser generates long pulses with 30 ps duration and 0.17 nm spectral width at 1530 nm wavelength. The source delivers an average power of 64 mW at a repetition rate of 16 MHz, corresponding to 4 nJ energy. This concept opens up new degrees of freedom in the design of mode-locked fiber lasers.

Aristolochic acid I (AAI) was regarded as the major toxic component of aristolochic acid (AA). In addition to aristolochic acid nephropathy (AAN), liver cancers induced by AAI has aroused increasing attention recently. In this paper, the discovery of diagnostic biomarkers for AAI-induced liver injury has been studied, especially for the lipid markers. From the histopathological characteristics, the injury was observed clearly in the liver apart from the kidney after 30 mg/kg of AA&Iota, treatment for one week, while the lesion alleviated after AA&Iota, discontinuance. The serum biochemical indexes were manifested to the normal tendency after AA&Iota, discontinuance for two weeks. According to the evaluation of pathology slices and serum biochemical indexes, they indicated that the hepatotoxicity induced by AA&Iota, was reversible to some extent. A total of 44 lipid markers were identified in the liver, as well as 59 in the serum. Twenty-six common lipid markers were observed in both serum and liver. Furthermore, nine out of 26 lipids exhibited the excellent diagnostic ability to differentiate the control group from the AA&Iota, group and AA&Iota, discontinuance group with high sensitivity and specificity. The changed lipid markers might serve as characteristics to explain the mechanisms of pathogenesis and progression in hepatotoxicity induced by AA&Iota