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Traditionally, the D1228 E/G/H/N mutation has been thought to cause Type I MET-TKI resistance. We reported a 75-year-old female with non-small cell lung cancer harboring MET exon 14 skipping mutation, who developed acquired MET D1228H mutation induced by capmatinib treatment. Interestingly, the patient demonstrated marked response to second-line savolitinib treatment with the duration of response of 19 months and several additional metastatic lesions appeared. Pathological assessment of rebiopsy sample showed adenocarcinoma and targeted next-generation sequencing revealed the loss of MET D1228H mutation and presence of MET p.Y1230N mutation. In response, the treatment regimen was amended to include a daily administration of 60 mg of cabozantinib, which resulted in moderate size reduction of the tumours. The switch of resistance mutations indicated that different type Ib MET inhibitors may exhibit distinct mechanisms of resistance. We call for futher studies on resistance based on patient-derived pre-clinical models including patient-derived tumor-like cell clusters, patient-derived organoids, and patient-derived xenografts. [ABSTRACT FROM AUTHOR]

Phospholipase A1 (PLA1) is a kind of specific phospholipid hydrolase widely used in food, medical, textile. However, limitations in its expression and enzymatic activity have prompted the investigation of the phospholipase-assisting protein PlaS. In this study, we elucidate the role of PlaS in enhancing the expression and activity of PlaA1 through N-terminal truncation. Our research demonstrates that truncating the N-terminal region of PlaS effectively overcomes its inhibitory effect on host cells, resulting in improved cell growth and increased protein solubility of the protein. The yeast two-hybrid assay confirms the interaction between PlaA1 and N-terminal truncated PlaS (∆N27 PlaS), highlighting their binding capabilities. Furthermore, in vitro studies using Biacore analysis reveal a concentration-dependent and specific binding between PlaA1 and ∆N27 PlaS, exhibiting high affinity. Molecular docking analysis provides insights into the hydrogen bond interactions between ∆N27 PlaS and PlaA1, identifying key amino acid residues crucial for their binding. Finally, the enzyme activity of PLA1 was boost to 8.4 U/mL by orthogonal test. Study significantly contributes to the understanding of the interaction mechanism between PlaS and PlaA1, offering potential strategies for enhancing PlaA1 activity through protein engineering approaches. [ABSTRACT FROM AUTHOR]

Traditional computing structures are blocked by the von Neumann bottleneck, and neuromorphic computing devices inspired by the human brain which integrate storage and computation have received more and more attention. Here, a flexible organic device with 2,7-dioctyl[1] benzothieno [3,2-b][1] benzothiophene (C8-BTBT) and 2,9-didecyldinaphtho [2,3-b:2′,3′-f] thieno [3,2-b] thiophene (C10-DNTT) heterostructural channel having excellent synaptic behaviors was fabricated on muscovite (MICA) substrate, which has a memory window greater than 20 V. This device shows better electrical characteristics than organic field effect transistors with single organic semiconductor channel. Furthermore, the device simulates organism synaptic behaviors successfully, such as paired-pulse facilitation (PPF), long-term potentiation/depression (LTP/LTD) process, and transition from short-term memory (STM) to long-term memory (LTM) by optical and electrical modulations. Importantly, the neuromorphic computing function was verified using the Modified National Institute of Standards and Technology (MNIST) pattern recognition, with a recognition rate nearly 100% without noise. This research proposes a flexible organic heterojunction with the ultra-high recognition rate in MNIST pattern recognition and provides the possibility for future flexible wearable neuromorphic computing devices. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine. [ABSTRACT FROM AUTHOR]

Although endoscopic necrosectomy (EN) is more frequently used to manage walled-off necrosis (WON), there is still debate over how much time should pass between the initial stent placement and the first necrosectomy. This study aims to determine the effect of performing EN within different timings after placing the initial stent on clinical outcomes for WON. A retrospective study on infected WON patients compared an early necrosectomy within one week after the initial stent placement with a necrosectomy that was postponed after a week. The primary outcomes compared the rate of clinical success and the need for additional intervention after EN to achieve WON resolution. 77 patients were divided into early and postponed necrosectomy groups. The complete resolution of WON within six months of follow-up was attained in 73.7% and 74.3% of patients in both the early and postponed groups. The early group tended to a greater need for additional intervention after EN (26.8% early necrosectomy vs. 8.3% postponed necrosectomy, P = 0.036). Our study does not demonstrate that early necrosectomy is superior to postponed necrosectomy in terms of clinical success rate, total count of necrosectomy procedures, procedure-related complications, length of hospitalization and prognosis. Conversely, patients in the postponed group received fewer additional interventions. [ABSTRACT FROM AUTHOR]

Cyanide-free electroplating processes offer a safe and environmentally friendly alternative to cyanide electroplating; however, challenges such as low deposition rates and inadequate densification need to be addressed. This paper proposes using laser electrochemical compound energy fields to optimize the 5,5-Dimethylhydantoin (DMH) cyanide-free electroplating process to achieve efficient and high-quality localized Au plating. The cleaning and activation effects of laser irradiation on substrates under-liquid cleaning were studied, and the results demonstrate that laser irradiation effectively removes oxide films from the 316 L stainless steel substrate, reducing surface roughness and enabling cleaning, leveling, and activation effects. Experimental investigations were conducted to analyze the impact of laser-induced thermal effects on the electrodeposition quality. The results show that the thermal accumulation effect of the laser facilitates the enhancement of the deposition rate and quality without exceeding the etching threshold of the plating. Additionally, the influence of laser parameters such as single pulse energy, scan spacing, scan rate, and pulse frequency on the surface morphology of Au plating was studied, and high-quality plating was prepared by optimizing parameters. The test results show that the denseness, corrosion resistance, and bonding of Au plating prepared by laser-induced electrodeposition (LIED) are better than those prepared by electrodeposition (ECD). [ABSTRACT FROM AUTHOR]

Introducing carbon quantum dots (CQDs) into photocatalysts is believed to boost the charge transfer rate and reduce charge complexation. Doping heteroatoms such as N, S, or P enable CQDs to have an uplifting electron transfer capability. However, the application of oxygen-doped CQDs to improve the performance of photocatalysts has rarely been reported. Herein, a type of carbon-oxygen quantum dots (COQDs) was in situ embedded into MIL-53(Fe) to aid peroxydisulfate (PDS)-activated degradation of oxytetracycline (OTC) under visible light irradiation. The successful embedding of COQDs was confirmed by XRD, FT-IR, XPS, SEM, and TEM techniques. Photoelectrochemical testing confirmed its better performance. The prepared COQDs1/MIL-53(Fe) showed 88.2% decomposition efficiency of OTC in 60 min, which was 1.45 times higher than that of pure MIL-53(Fe). In addition, the performance of the material was tested at different pH, OTC concentrations, catalyst dosing, and PDS dosing. It was also subjected to cyclic testing to check stability. Moreover, free radical trapping experiments and electron paramagnetic resonance were conducted to explore the possible OTC deterioration mechanism. Our work provides a new idea for the development of MOFs for water treatment and remediation. [ABSTRACT FROM AUTHOR]

At present, traditional Chinese medicine treatment is considered safe for treating peripheral facial paralysis (PFP). Acupuncture-only and acupuncture combined with tuina are widely used for this purpose. However, it is not clear whether acupuncture combined with tuina is better for treating PFP than acupuncture-only. Conventional meta-analysis and network meta-analysis were used to compare the clinical efficacies of acupuncture combined with tuina and acupuncture-only in the treatment of PFP. Randomized controlled trials (RCTs), with the subjects being patients with PFP and treatment interventions including acupuncture combined with tuina, acupuncture-only, tuina-only, placebo, single Western medicine, and steroids combined with other Western medicine were searched from both Chinese and English databases. The primary outcomes included Modified House–Brackmann (MHBN) scores and Sunnybrook Facial Grading System, whereas the secondary outcomes included cure time, Portmann scores, and physical function scale of Facial Disability Index, using conventional meta-analysis and network meta-analysis. The study included 22 RCTs with a sample size of 1814 patients. The results of conventional meta-analysis (MD = 16.12, 95%CI 13.13,19.10) and network meta-analysis (MD = 14.53, 95%CI 7.57,21.49) indicate that acupuncture combined with tuina was better than acupuncture-only in improving MHBN and shortening the cure time (MD = − 6.09, 95%CI − 7.70, − 4.49). Acupuncture combined with tuina was the optimal therapy for improving MHBN (SUCRA was 100%) and shortening the cure time (SUCRA was 100%). The results of this meta-analysis indicate that acupuncture combined with tuina can significantly improve MHBN and shorten the cure time, compared with acupuncture-only. However, the current evidence is insufficient, and more high-quality clinical studies are needed. Registration: This study had been registered with PROSPERO (CRD42022379395). [ABSTRACT FROM AUTHOR]

Global warming threatens freshwater ecosystems and compromises fish survival. To elucidate the role of miRNAs in the livers of heat stressed largemouth bass, juvenile fish was subject to heat stress under 37 °C. Both mRNA-seq and miRNA-seq were conducted on the liver tissues under control and heat stress conditions. Differential gene expression analysis and enrichment analysis were performed on mRNA and miRNA expression profiles. A total of 406 differentially expressed genes (DEGs) were discovered, of which 212 were up-regulated and 194 were down-regulated. Most of the DEGs were significantly implicated in the regulation of "protein processing in endoplasmic reticulum", "proteasome", "steroid biosynthesis", and "ornithine decarboxylase inhibitor activity" pathways. In addition, 47 differentially expressed miRNAs (DEMs) were identified in largemouth bass livers under heat stress, including 21 up-regulated and 25 down-regulated miRNAs. A negatively regulated miRNA-mRNA network including 12 miRNAs and 19 mRNAs was constructed with DEMs involved in "protein degradation", "calcium ion regulation", "cell apoptosis", and "lipid metabolism". Moreover, this study indicated novel-miR-144 activated the IRE1 signaling pathway by targeting txndc5 to induce liver apoptosis in largemouth bass under heat stress. This study revealed the involvement of miRNA regulation in largemouth bass in response to heat stress. [ABSTRACT FROM AUTHOR]

Microbubble reactors play an important role in the development of gas-liquid reaction process enhancement. However, the urgent demand for high efficiency and low energy consumption in gas-liquid reaction processes, as well as the trend towards large-scale production, have put forward higher requirements for the design and optimization of microbubble reactors. In this study, a self-priming microbubble reactor was designed and its structure parameters were optimized by (computational fluid dynamics) CFD simulations. Based on the grid division method combining structured and unstructured grids, the most suitable mesh number is selected, and the simulation calculation time is saved on the premise of ensuring the accuracy. The effects of five structural parameters on the gas content and energy loss was discussed and the optimal structural parameters of the microbubble reactor were determined as follows: the diffusion section length is 75 mm, the contraction angle is 22°, the diffusion angle is 10.5°, the inlet diameter of the gas phase is 6 mm, the inlet diameter of the liquid phase flowing into the gas chamber is 3 mm, the diffusion section inlet diameter is 5 mm. Under the condition of the same inlet flow rate, the outlet gas content of the optimized gas-liquid reactor is increased by 42.9% compared with the initial structure. In the wastewater treatment experiment, the microbubble reactor reduced the chemical oxygen demand of wastewater by 61% within three hours. This study provides significant references for the design of the self-priming microbubble reactor. [ABSTRACT FROM AUTHOR]

The power of three-dimensional printing in designing personalized scaffolds with precise dimensions and properties is well-known. However, minimally invasive implantation of complex scaffolds is still challenging. Here, we develop amphiphilic dynamic thermoset polyurethanes catering for multi-material four-dimensional printing to fabricate supportive scaffolds with body temperature-triggered shape memory and water-triggered programmable deformation. Shape memory effect enables the two-dimensional printed pattern to be fixed into temporary one-dimensional shape, facilitating transcatheter delivery. Upon implantation, the body temperature triggers shape recovery of the one-dimensional shape to its original two-dimensional pattern. After swelling, the hydrated pattern undergoes programmable morphing into the desired three-dimensional structure because of swelling mismatch. The structure exhibits unusual soft-to-stiff transition due to the water-driven microphase separation formed between hydrophilic and hydrophobic chain segments. The integration of shape memory, programmable deformability, and swelling-stiffening properties makes the developed dynamic thermoset polyurethanes promising supportive void-filling scaffold materials for minimally invasive implantation. 3D printing has potential in designing personalised scaffolds, but minimally invasive implantation is still challenging. Here, the authors report the development of a polyurethane material with temperature triggered shape memory and water triggered deformation that allows for transcatheter delivery. [ABSTRACT FROM AUTHOR]

The amount of digital music available on the internet has grown significantly with the rapid development of digital multimedia technology. Managing these massive music resources is a thorny problem that powerful music media platforms need to face where music genre classification plays an important role, and a good music genre classifier is indispensable for the research and application of music resources in the related aspects, such as efficient organization, retrieval, recommendation, etc. Due to convolutional networks' powerful feature extraction capability, more and more researchers are devoting their efforts to music genre classification models based on convolutional neural networks (CNNs). However, many models do not combine the musical signal features for effective design of the convolutional structure, which cause a simpler convolutional network part of the model and weaker local feature extraction ability. To solve the above problem, our group proposes a model using a 1D res-gated CNN to extract local information of audio sequences rather than the traditional CNN architecture. Meanwhile, to aggregate the global information of audio feature sequences, our group applies the Transformer to the music genre classification model and modifies the decoder structure of the Transformer according to the task. The experiments utilize the benchmark datasets, including GTZAN and Extended Ballroom. Our group conducted contrastive experiments to verify our model, and experimental results demonstrated that our model outperforms most of the previous approaches and can improve the performance of music genre classification. [ABSTRACT FROM AUTHOR]

The current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job. Even with the observed increase in academic programs related to pharmacometrics, this need is unlikely to change in the foreseeable future, as the demand and scope of pharmacometrics applications keep expanding. Further, the field of pharmacometrics is changing. The field largely started when Lewis Sheiner and Stuart Beal published their seminal papers on population pharmacokinetics in the late 1970's and early 1980's and has continued to grow in impact and use since its inception. Physiological-based pharmacokinetics and systems pharmacology have grown rapidly in scope and impact in the last decade and machine learning is just on the horizon. While all these methodologies are categorized as pharmacometrics, no one person can be an expert in everything. So how do you train future pharmacometricians? Leading experts in academia, industry, contract research organizations, clinical medicine, and regulatory gave their opinions on how to best train future pharmacometricians. Their opinions were collected and synthesized to create some general recommendations. [ABSTRACT FROM AUTHOR]

This paper presents an analysis on a geogrid-reinforced embankment with clay-cover by model tests under static and cyclic loading. The deformation and failure surface inside the embankment were obtained by particle image velocimetry (PIV). The test results showed that geogrids effectively improved the ultimate bearing capacity and reduced the vertical settlement and lateral displacement of reinforced embankment. The reinforcement effect increased with the increase in geogrid length, and the ultimate bearing capacity of the embankment reinforced with the longest geogrid was 51.9 kPa, which was 79% higher than that of unreinforced embankment. The wrapped clay formed an effective lateral constraint on the outward movement of the slope soil under pressure. When the reinforced embankment was damaged, the internal displacement significantly reduced, and the sliding surface in the middle of the embankment pointing to the foot of slope began to move into the embankment in an arc shape. In the cyclic loading test, the stress concentration effect inside embankment reduced by geogrid reinforcement. During each cycle, the earth pressure varied with a stable half-sine wave. The conclusions drawn from this study can provide an important fundamental data for the construction in geotechnical and road engineering. [ABSTRACT FROM AUTHOR]

Artificial intelligence models play a crucial role in monitoring and maintaining railroad infrastructure by analyzing image data of foreign objects on power transmission lines. However, the availability of publicly accessible datasets for railroad foreign objects is limited, and the rarity of anomalies in railroad image data, combined with restricted data sharing, poses challenges for training effective foreign object detection models. In this paper, the aim is to present a new dataset of foreign objects on railroad transmission lines, and evaluating the overall performance of mainstream detection models in this context. Taking a unique approach and leveraging large-scale models such as ChatGPT (Chat Generative Pre-trained Transformer) and text-to-image generation models, we synthesize a series of foreign object data. The dataset includes 14,615 images with 40,541 annotated objects, covering four common foreign objects on railroad power transmission lines. Through empirical research on this dataset, we validate the performance of various baseline models in foreign object detection, providing valuable insights for the monitoring and maintenance of railroad facilities. [ABSTRACT FROM AUTHOR]

In this paper, we concentrate on a non-orthogonal multiple access (NOMA)-enabled UAV data collection network for Internet of Things devices (IoTDs), where a unmanned aerial vehicle (UAV) is deployed as an aerial base station. During its flight period, the UAV can collect data from IoTDs and take advantage of the simultaneous wireless information and power transfer technology to charge the batteries of IoTDs. With the aid of NOMA, spectrum efficiency has been improved. We aim to prolong the lifetime of the IoT network, via jointly optimizing the UAV trajectory, the time allocation for information communication and wireless power transfer, the IoTDs' transmit power, as well as the IoTDs' group scheduling for NOMA. Then, we use the block coordinate decent and successive convex approximation techniques to tackle the non-convexity of the formulated problem. Numerical results show that the proposed solution increases the residual energy of the IoTDs, thus prolonging the lifetime of the network. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. Methods: This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). Results: Safety analyses included 667 patients (female, 82.3%; mean age, 53.3 years; mean RA duration, 86.9 months); 106/667 (15.9%) were 65–74 years old and 19/667 (2.8%) were ≥ 75 years old; 87.0% received baricitinib 2 mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100 PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. Conclusions: This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. Trial Registration: EU PAS Register: EUPAS34213. [ABSTRACT FROM AUTHOR]

To solve the problem that twist springback of thin-walled component with asymmetric complex section cannot meet the high-precision quality requirement, FEA (finite element analysis) model of multi-pass roll forming (RF) process is established. Different material constitutive models are verified with RF tests, and the developed FEA model with variable elastic modulus and Yld2000 yield criterion is carried out to predict twist springback accurately. The mechanism of twist springback is studied by numerical simulations that twist springback results from the torque produced with the uneven residual longitudinal stress distribution due to the asymmetric forming for asymmetric section. The effect of different forming strategies on twist springback is discussed that developed UDT-type (USTB-Durable T) method with constant-arc-length method can effectively control twist springback. Orthogonal test is designed to study the effect of process parameters on twist springback. Results indicate that forming stands has the greatest impact on twist angle, followed by roll diameter and inter-distance, and roll gap has the smallest impact. The developed design and forming parameters are applied to control twist springback of asymmetric complex-section product. The actual product is deformed in industrial production line with the twist angle of less than 2 ∘ / m to meet high-precise quality requirement. [ABSTRACT FROM AUTHOR]

TB6 titanium alloy has the characteristics of high strength, high fatigue life, and low stiffness, making it a favored choice for critical load-bearing components in helicopters and large passenger aircraft. However, it is difficult to realize efficient and high-quality processing of TB6 by using traditional mechanical cutting technology because of its inherent characteristics. Electrochemical jet machining technology can dissolve materials through electrochemistry, which has prominent advantages such as no cutting force and high processing flexibility, making it a promising method for achieving efficient and high-quality TB6 titanium alloy processing. This paper focuses on the electrochemical dissolution behaviors of TB6 titanium alloy, as well as the electrochemical jet machining characteristics. The current efficiency and polarization curves of TB6 titanium alloy in different solutions were tested at different temperatures. The phenomenon of bubble generation and black product falling during the test was captured. The surface dissolution process of TB6 titanium alloy at different current densities was investigated through scanning electron microscope pictures. Finally, the electrochemical jet machining experiment was conducted. The surface characteristics of the micro-grooves obtained by electrochemical jet machining, including morphology, cross-sectional profile, and surface roughness, were explored. The research findings revealed that, at high current densities exceeding 200 A/cm2, electrochemical dissolution exhibited greater uniformity while stray corrosion was significantly reduced. Excellent surface quality with a minimum surface roughness of Ra 0.373 μm was achieved in electrochemical jet machining of TB6 titanium alloy with 20 wt% NaCl solution. [ABSTRACT FROM AUTHOR]

Objective: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. Methods: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. Results: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. Conclusions: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy. [ABSTRACT FROM AUTHOR]

The level set method is a classical method to solve the Chan-Vese model for the binary image segmentation problem. Some efficient methods such as the convex relaxed methods and the steep descent methods based on a suitable constraint have been proposed to overcome the singularity of the LSM. However, the effectiveness of using these schemes is still limited by the chosen threshold value or the Courant-Friedrichs-Lewy condition. To this end, this paper, based on the Lagrangian dual scheme from the numerical optimization theory, proposes a novel numerical method to solve the CV model. Specifically, the binary constraint of the level set function can be transformed into a nonsmooth optimization problem via the help of the Lagrangian dual scheme. Then the Dual-based Alternating Direction of Method of Multipliers can be employed to solve this transform form. Numerical experiments show that the average (± std.dev) Segmentation Error (SE) of the proposed method on two groups of synthetic images are 5.59%(± 0.19%) and 5.01%(± 3.61%). The Precision, Segmentation Accuracy (SA) and F1-Score (F1S) of natural gray and natural color image reach 75.17%(± 12.42%), 98.87%(± 1.16%), 94.99%(± 5.23%) and 81.91%(± 14.85%), 98.38%(± 0.99%), 86.39%(± 11.72%), respectively, which are better than the other three comparison schemes. Therefore, our proposed method is more robust to initialization, faster and more accurate than three classical methods to solve the CV model. [ABSTRACT FROM AUTHOR]

Introduction: Polymorphisms in the Thiopurine S-Methyltransferase (TPMT) gene are associated with decreased TPMT activity, but little is known about their impact on TPMT protein expression in the liver. This project is to conduct a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with altered TPMT protein expression in human livers and to determine if demographics affect hepatic TPMT protein expression. Methods: Human liver samples (n = 287) were genotyped using a whole genome genotyping panel and quantified for TPMT protein expression using a Data-Independent Acquisition proteomics approach. Results and Discussion: Thirty-one SNPs were found to be associated with differential expression of TPMT protein in the human livers. Subsequent analysis, conditioning on rs1142345, a SNP associated with the TPMT*3A and TPMT*3C alleles, showed no additional independent signals. Mean TPMT expression is significantly higher in wildtype donors compared to those carrying the known TPMT alleles, including TPMT*3A, TPMT*3C, and TPMT*24 (0.107 ± 0.028 vs. 0.052 ± 0.014 pmol/mg total protein, P = 2.2 × 10−16). After removing samples carrying the known TPMT variants, European ancestry donors exhibited significantly higher expression than African ancestry donors (0.109 ± 0.026 vs. 0.090 ± 0.041 pmol/mg total protein, P = 0.020). Conclusion: The GWAS identified 31 SNPs associated with TPMT protein expression in human livers. Hepatic TPMT protein expression was significantly lower in subjects carrying the TPMT*3A, TPMT*3C, and TPMT*24 alleles compared to non-carriers. European ancestry was associated with significantly higher hepatic TPMT protein expression than African ancestry, independent of known TPMT variants. [ABSTRACT FROM AUTHOR]

This paper presents a WR-2.2 band waveguide orthogonal mode transducer (OMT) for an ice cloud remote sensing radiometer. A holistic approach is proposed to the design and manufacturing. Given the difficulties of using computer numerically controlled (CNC) milling techniques to fabricate the OMT and its assembly, both the design and fabrication processes are optimized to reduce the possibility of error, which could affect OMT performance. In the design, the OMT utilizes a side-arm structure, with a compact 90° waveguide twist designed in the side-arm path to reduce insertion loss and achieve two symmetric and opposing output ports in the radiometer. Regarding the challenges in CNC milling technology for such high frequencies, a comprehensive sensitivity analysis is performed following the OMT design to identify the design parameters with high sensitivity. Then, an acceptable tolerance range for CNC milling is obtained. To control fabrication uncertainty and minimize tolerance, an effective fabrication refinement strategy is proposed for accessible CNC machining, reducing the range of fabrication errors to − 3 to 2 µm within 3 iterations. Comprehensive measurements and analyses are performed on the fabricated OMT as well as the one with an antenna and a receiver. The measured insertion losses of the H and V copolarization of the OMT are better than 1.4 dB and 2 dB, respectively. The isolation is better than 40 dB. The measured H and V cross-polarizations are better than 25 dB. They demonstrate the OMT with a good performance for radiometer system. [ABSTRACT FROM AUTHOR]

Novel view synthesis using implicit neural functions such as Neural Radiance Field (NeRF) has achieved significant progress recently. However, it is very computationally expensive to train a NeRF due to the disordered frequency optimization. In this paper, we propose the Pyramid NeRF, which guides the NeRF training in a 'low-frequency first, high-frequency second' style using the image pyramids and could improve the training and inference speed at 15 × and 805 × , respectively. The high training efficiency is guaranteed by (i) organized frequency-guided optimization could improve the convergency speed and efficiently reduce the training iterations and (ii) progressive subdivision, which replaces a single large multi-layer perceptron (MLP) with thousands of tiny MLPs, could significantly decrease the execution time of running MLPs. Experiments on various synthetic and real scenes verify the high efficiency of the Pyramid NeRF. Meanwhile, the structure and perceptual similarities could be better recovered. [ABSTRACT FROM AUTHOR]

A high-performance grouting material is proposed to enhance the support effect of anchoring pipes in soft rock mass tunnels in this paper. Through mix proportion and strength tests, the initial setting time, compressive strength, and flowability of the grouting material were determined. Furthermore, based on grouting and pulling tests, the recommended parameters of the anchoring pipe were proposed. The results show that pure cement paste is an ideal grouting material for on-site application, demonstrating excellent anchoring, fluidity, high strength, and rapid hardening. Under optimal conditions of water-cement ratio at 0.46 and retarder proportion at 0.4‰, the initial settling time and the compressive strength of the grouting material are approximately 45 minutes and 28.5 MPa within 4 hours, respectively. The anchoring force of an anchoring pipe with a length of 6 m and a diameter of 76 mm can reach 448.9 kN within the same period. A field test involving anchoring pipes and pure cement paste was conducted during tunnel construction, resulting in a substantial reduction of maximum settlement and convergence of the tunnel by 57.53% and 40.48%, respectively. These results demonstrate the effectiveness of the proposed material and anchoring pipe in controlling deformation in soft rock tunnels. [ABSTRACT FROM AUTHOR]

This study investigated the effect of heat stress on the physiological parameters, oxidation resistance ability and immune responses in juvenile hybrid yellow catfish. Heat stress group exposed to 35 °C and control to 28 °C. Blood and liver were sampled at different hours' post-exposure. Results showed that red blood cell (RBC), white blood cell (WBC) counts, Hemoglobin (HGB) levels and hematocrit (HCT) values increased significantly (P < 0.05) post-exposure to heat stress. This indicates the increase of cell metabolism. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, total cholesterol (TC), total protein (TP), triglyceride (TG) and glucose increased significantly (P < 0.05) indicating the need to cope with stress and cell damage. Liver TC, TG, COR hormone, C3 complement increased significantly from 24 to 96 h. Heat stress mostly affects the hepatic antioxidant and immune resistance functions, resulting in increments of cortisol levels, lysozyme, superoxide dismutase (SOD), and catalase (CAT) enzyme activities. The increase of Malondialdehyde (MDA), alkaline phosphatase (AKP) indicate stimulation of the immune responses to protect the liver cells from damage. The decrease in Liver TP indicated liver impairment. Decrease in Glycogen content from 6 to 96 h indicated mobilization of more metabolites to cope with increased energy demand. Interestingly, results showed that heat stress trigged costly responses in the experimental fish like accelerated metabolism and deplete energy reserves, which could indirectly affect ability of fish to set up efficient long term defense responses against stress. These results provide insight into prevention and management of stress in juvenile hybrid yellow catfish. [ABSTRACT FROM AUTHOR]

A large number of studies have indicated that Chinese herbaceous polysaccharides possessed immune-promoting effects in animal husbandry. However, the function of Salvia miltiorrhiza polysaccharides (SMP) in fish remains poorly understood. In the present study, juvenile hybrid sturgeons (Acipenser baerii♀ × Acipenser schrenckii♂) were studied to assess the effects of SMP on growth performance, antioxidant capacity, non-specific immunity, and resistance to Streptococcus iniae. The results showed that weight gain rate, specific growth rate, and daily growth coefficient had no difference from those of the control group, but 0.1% SMP significantly increased the thickness of muscle layer and height and number of intestinal villus (P < 0.05). 0.5% and 0.7% SMP could significantly increase the T-AOC activity in the liver and valvular intestine, along with 0.5% SMP that significantly decreased the MDA content in the liver (P < 0.05). Moreover, all experimental groups could significantly increase serum TP and GLO contents. After infection with S. iniae, the survival rate of the experimental groups was higher than that of the control group, especially in 0.5% SMP group. In conclusion, dietary supplementation of SMP could enhance the antioxidant and non-specific immune capacity of hybrid sturgeon, thus improving disease resistance and promoting the healthy breeding of juvenile hybrid sturgeon. Our findings provide novel recommendations for the application of SMP supplementation in farmed fish. [ABSTRACT FROM AUTHOR]

Psoriasis, an inflammatory autoimmune skin disease, is characterized by scaly white or erythematous plaques, which severely influence patients' quality of life and social activities. Mesenchymal stem cells derived from the human umbilical cord (UCMSCs) represent a promising therapeutic approach for psoriasis because of its unique superiority in ethical agreeableness, abundant source, high proliferation capacity, and immunosuppression. Although cryopreservation provided multiple benefits to the cell therapy, it also greatly compromised clinical benefits of MSCs due to impaired cell functions. The current study aims to evaluate the therapeutic efficacy of cryopreserved UCMSCs in a mouse model of psoriasis as well as in patients with psoriasis. Our results showed that cryopreserved and fresh UCMSCs have comparable effects on the suppression of psoriasis-like symptoms such as thickening, erythema, and scaling, and serum IL-17 A secretion in mice model of psoriasis. Moreover, psoriatic patients injected with cryopreserved UCMSCs had a significant improvement in the Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), and Patient Global Assessments (PtGAs) scores compared to baseline values. Mechanically, cryopreserved UCMSCs markedly inhibit the proliferation of PHA-activated PBMCs, type 1 T helper (Th1) and type 17 T helper (Th17) cell differentiation and secretion of inflammatory cytokines including IFN-γ, TNF-a and IL-17 A in PBMCs stimulated by anti-CD3/CD28 beads. Taken together, these data indicated that cryopreserved UCMSCs exhibited great beneficial effect on psoriasis. Thus, cryopreserved UCMSCs can be systemically administered as "off-the-shelf" cell product for psoriasis therapy. Trial Registration ChiCTR1800019509. Registered on November 15, 2018—Retrospectively registered, http://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

The degradation of components resulted from wear is unavoidable in service, which could be partly solved by applying surface treatment technique. Stellite-6 cobalt-based alloy is considered as a potential cladding material to improve the wear resistance of base materials owing to its excellent hardness and strength. The microstructural evolution and local mechanical properties of Co-rich matrix and Cr-rich eutectic carbide of Stellite-6 cladding with different aging times at 900 °C are investigated by optical microscopy, field emission scanning electron microscope and nanoindentation testing. The tribological characteristics of the matrix and eutectic carbide itself are systematically investigated using the single-pass nano-scratch testing. In the matrix region, the carbide precipitations occur after 5 h and coarsens after 10 h aging. The nanoindentation results indicate that the hardness of the matrix regions is significantly increased due to the presence of dispersed carbide and fine stripe-like precipitations. The nano-scratch tests depict that the wear resistance is improved with higher matrix hardness to support eutectic carbide based on aging treatment. Potential improvement on tribological performance through the aging treatment procedure is proved based on the micromechanical and wear behaviors of matrix and eutectic carbide were identified. [ABSTRACT FROM AUTHOR]

Laser-induced plasma-assisted ablation (LIPAA) is a promising microfabrication method. In the experiment, a piece of transparent material (quartz) was placed above the absorption material (copper plate). The effects of laser fluence, repetition rate, and scan speed on the results and their mechanism were analyzed. The changes of micro-texture size, copper content, and contact angle (CA) on quartz surface were discussed. The micro-texture height keeps between 2.6 and 3.1 μm when the repetition rate increases to 2.5 MHz. The micro-texture size increased with the laser fluence and decreased with the scan speed. The copper content reached a maximum of 39% at 1.91 MW/cm2 and 2.5 MHz. The quartz surface processing area achieves hydrophobic performance without any post-treatment. The CA reached its optimal value of 146° at 900 mm/s and 2 MHz. There is a correlation between hydrophobicity and micro-texture size. The research results can provide a reference for optimizing the LIPAA parameters of quartz. The studied LIPAA method can potentially be employed for the fast and effective fabrication of hydrophobic surfaces without post-treatment. [ABSTRACT FROM AUTHOR]

Relaxor ferroelectric capacitors receive extensive attention for the energy storage applications due to their slim polarization–electric field hysteresis loops. Typically, relaxor ferroelectrics can be designed through introducing multiple heterovalent cations in the ferroelectrics to break the long-range ferroelectric order and form polar nanoregion. Here, medium-entropy relaxor ferroelectric (Bi0.7Na0.67Li0.03)0.5Sr0.3TiO3 (BNLST) thin films with A-site chemical heterogeneity, synthesized by a chemical solution method, are studied as dielectric capacitors for the energy storage application. Mn doping is utilized to occupy cation vacancies to improve the electrical properties. High energy density (47 J cm−3), good efficiency (69%), and good frequency, temperature and fatigue stability are obtained simultaneously. These results show the potential applications of SBNLT relaxor ferroelectric thin film for dielectric energy storage. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory disorders of the central nervous system targeting aquaporin‐4 (AQP4). The risk factors for NMOSD remain to be determined, though they may be related to diet and nutrition. This study aimed to explore the possibility of a causal relationship between specific food intake and AQP4-positive NMOSD risk. The study followed a two-sample Mendelian randomization (MR) design. Genetic instruments and self-reported information on the intake of 29 types of food were obtained from a genome-wide association study (GWAS) on 445,779 UK Biobank participants. A total of 132 individuals with AQP4-positive NMOSD and 784 controls from this GWAS were included in our study. The associations were evaluated using inverse-variance-weighted meta-analysis, weighted-median analysis, and MR-Egger regression. A high consumption of oily fish and raw vegetables was associated with a decreased risk of AQP4-positive NMOSD (odds ratio [OR] = 1.78 × 10−16, 95% confidence interval [CI] = 2.60 × 10−25–1.22 × 10−7, p = 0.001; OR = 5.28 × 10−6, 95% CI = 4.67 × 10−11–0.598, p = 0.041, respectively). The results were consistent in the sensitivity analyses, and no evidence of directional pleiotropy was observed. Our study provides useful implications for the development of AQP4-positive NMOSD prevention strategies. Further research is needed to determine the exact causal relationship and mechanisms underlying the association between specific food intake and AQP4-positive NMOSD. [ABSTRACT FROM AUTHOR]

Exposure–response (E–R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and external drug development questions (e.g., optimal dose, frequency of administration, dose adjustments for special populations). This white paper is the output of an industry-government collaboration among scientists with broad experience in E–R modeling as part of regulatory submissions. The goal of this white paper is to provide guidance on what the preferred methods for E–R analysis in oncology clinical drug development are and what metrics of exposure should be considered. [ABSTRACT FROM AUTHOR]

How to improve charging processes and suppress self-discharging processes has always been one of the key issues to achieve quantum batteries with high performance. Although a quantum battery is inevitably influenced by composite environments, this situation is still little understood, particularly regarding the influence of the memory effect of the composite environments and the coupling between composite environments. In this work, we investigate the effects of the composite environments, composed of two identical parts each containing a single cavity mode decaying to a reservoir, on the charging and self-discharging processes of a quantum battery. We show that increasing the two-mode coupling can effectively enhance the charging performance (i.e., the stored energy, the charging power, ergotropy) and restrain the self-discharging process (i.e., suppressing the process of dissipating the energy). However, different from the effect of two-mode coupling, we reveal that the memory effect of the reservoir in this composite environment is unfavorable to the charging process of the quantum battery, which is in sharp contrast to previous studies where the memory effect can significantly improve the charging performance of a quantum battery. Our results may benefit to the realization of quantum batteries with high performance under the actual complex environmental noise. [ABSTRACT FROM AUTHOR]

Relaxor ferroelectric thin films, that demonstrate high energy storage performances due to their slim polarization–electric field hysteresis loops, have attracted extensive attentions in the application of miniaturized advanced pulsed power electronic systems. However, the ubiquitous defects induced in the thin films, for example, due to the volatilization of cations, limit the energy storage performance to a great extent due to the reduced breakdown strength. Here, the shallow trap defects, but not the oxygen vacancy, in 0.9Sr0.7Bi0.2TiO3-0.1BaTiO3 (SBT-BT) relaxor ferroelectric thin films are effectively suppressed by the Mn doping. An improved high energy storage density of 55 J/cm3 and an optimized high energy storage efficiency of 80.9% are achieved in the Mn-doped SBT-BT relaxor ferroelectric thin films, and high fatigue resistance, frequency and temperature stability are also achieved simultaneously. These results indicate this SBT-BT-based relaxor ferroelectric thin films exhibit high energy storage performance and can be used as an important component in energy storage electrical and electronic systems. More importantly, this work provides an effective approach to achieve high energy storage performances by shallow trap defect quenching. [ABSTRACT FROM AUTHOR]

Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3. Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance. Most cases of craniofacial microsomia are sporadic but familial cases have been reported. Here the authors report that variants in FOXI3 can cause a small fraction of cases with different modes of inheritance including autosomal dominant with reduced penetrance. [ABSTRACT FROM AUTHOR]

On the basis of first-principles calculations, we investigate the electronic and magnetic properties of 1T phase chromium sulfide halide CrXY (X = O, S, Se; Y = Cl, Br, I) monolayers in CrCl2 structure with the P 3 ¯ m1 space group. Except for the CrOI monolayer, all CrXY monolayers are stable and ferromagnetic semiconductors. Our results show that the ferromagnetic coupling is dominated by the kinetic exchange between the empty eg-orbital of Cr atoms and the p-orbital of anions under the three-fold rotational symmetry. In this context, the coupling strength allows for being greatly enhanced by turning the nature of Cr–X bonds, i.e., increasing the covalent contribution of the bonds by minimizing the energy difference of the coupled orbitals. As we illustrate for the example of CrOY, the Curie temperature (Tc) is nearly tripled by substituting O by S/Se ion, eventually reaching the highest Tc in CrSeI monolayer (334 K). The high stabilities and Curie temperature manifest these monolayer ferromagnetic materials feasible for synthesis and applicable to 2D spintronic devices. [ABSTRACT FROM AUTHOR]

Hatching enzyme (HE) is the most critical enzyme in the process of fish hatching. Pikeperch, Sander lucioperca, is one of economical and ferocious fish with long embryonic incubation and its long and irregular hatching time easily leads to the decrease of its fingerlings due to cannibalism. HE is one of the most important factors that affect the membrane effusion of fish eggs during incubation. The present study aimed to clone HE genes and to reveal the HE expression patterns of pikeperch during its hatching process. In this study, the full-length cDNAs of high choriolytic enzyme gene (HCE) and low choriolytic enzyme gene (LCE) from pikeperch were cloned and their expressions were performed using qRT-PCR and in situ hybridization. The results showed that the full-length cDNAs of HCE and LCE were comprised of 1189 bp and 1147 bp, respectively, and the open reading frames (ORFs) obtained were 876 bp and 798 bp, encoded proteins of 291 and 265 amino acids, respectively. Phylogenetic analysis showed high homology of HE in Percidae, far from amphibians, birds, and insects. HE genes maintained high expression from body segment appearance stage to hatching stage, and low expression in early embryo and larval stage of pikeperch. HE transcripts were initially detectable at body segment appearance stage in the head region and on the surface of the yolk sac. At hatching stage, strong staining was observed in the whole body from head to the tail. Compared with other fishes, the special spatiotemporal expression pattern of hatching enzyme may be the key factor leading to the irregular hatching time of pikeperch. Our study might enhance our understanding of the hatching mechanism of pikeperch. [ABSTRACT FROM AUTHOR]

Scientific and reasonable premium rate is the premise to guarantee the high-quality development of agricultural insurance, while unscientific premium rate is the important reason for adverse selection and insufficient use of financial funds in the development of agricultural insurance. Using the method of leading indicators and cluster analysis, this paper have regionalized the planting risk of jujube at the county level in Aksu Region of Xinjiang, China. The mixed Copula-stochastic optimization model have been used to determine the premium rate of jujube revenue insurance in different planting risk areas. Under the 100% guarantee level, the amount of revenue insurance for jujube in low, medium, higher and highest risk areas are 28,026.72 yuan/ha, 25,969.49 yuan/ha, 29,149.02 yuan/ha and 12,256.68 yuan/ha, respectively. The gross rate are 12.79%, 15.17%, 47.99% and 12.65% respectively, and the premium are 3585.93 yuan/ha, 3939.84 yuan/ha, 13,988.87 yuan/ha and 1550.44 yuan/ha respectively. In addition to the highest-risk area due to low insurance amount resulting in lower rates and premiums, the rates and premiums of the other three risk areas are consistent with the effect of their risk levels. In this paper, we propose a new pricing method of crop revenue insurance, which has a good theoretical significance for improving the credibility of crop revenue insurance pricing results, and has an important practical significance for changing the "unified" mode of current policy insurance reward and subsidy scheme of forestry and fruit industry in Xinjiang. [ABSTRACT FROM AUTHOR]

Inspired by animals or plants in nature, the surface of many industrial products is endowed with superhydrophobic properties according to the principle of bionics, thus solving multiple industrial problems, such as self-cleaning, underwater drag reduction, droplet or bubble control, delayed icing, corrosion prevention, biomimetic deposition, optical applications, anisotropy, oil–water separation and so on. As an advanced method for preparing superhydrophobic surfaces, laser biomimetic manufacturing has the characteristics of high efficiency, flexibility and controllability. Therefore, laser biomimetic manufacturing technology has received extensive attention in recent years, and has been widely studied in the superhydrophobic fields. This paper highlights the latest research progress of application of functional superhydrophobic surface prepared by laser biomimetic manufacturing. Finally, the future research directions for functional superhydrophobic surface are discussed, and the development has been prospected. [ABSTRACT FROM AUTHOR]

A large number of pathogenic bioaerosols are generated during the treatment process of wastewater treatment plants (WWTPs), and they can pose potential risks to human health. Therefore, this study systematically analyzed the emission characteristics of Staphylococcus aureus bioaerosols released from an inverted umbrella aeration tank, a microporous aeration tank, and a residual sludge storage yard in a WWTP, and quantitatively evaluated the health risks of four kinds of exposed populations with nasal/oral breathing patterns under optimistic and conservative estimations. The results displayed that the bioaerosol concentration in inverted umbrella aeration tank was higher than that in microporous aeration tank and residual sludge storage yard. Aerosolization ratio in residual sludge storage yard was an order of magnitude lower than that in aeration tanks. Sludge workers were at higher health risks than the other three exposed populations. The health risks of nasal breathers (infection risk: 1.62 × 10−5–2.56 × 10−3 pppy; disease burden: 4.24 × 10−8–6.72 × 10−6 DALYs pppy) were 0.61–0.63 times higher than those of oral breathers (infection risk: 9.95 × 10−6–1.59 × 10−3 pppy; disease burden: 2.61 × 10−8–4.18 × 10−6 DALYs pppy). For female field engineers using oral breathing, laboratory technicians, and researchers without personal protective equipment (PPE), infection risk and disease burden had the opposite results, which indicated that satisfying one certain benchmark did not mean absolute safety. In addition, health risks of exposed populations were reduced by an order of magnitude after wearing PPE. This study can provide a reliable theoretical basis for the risk prevention of bioaerosols and supply data support for the strategies of health risk control perspectives for local sewage utilities. [ABSTRACT FROM AUTHOR]

With the rapid development of the Internet of Vehicles (IOV), how to effectively distributed content in IOV has been a key issue. To tackle this problem, vehicular edge computing is proposed as an effective solution. However, The expensive cost of deploying infrastructures such as roadside unit (RSU), which limits the range of content distribution. Besides, the rapid mobility of the vehicle seriously affects the efficiency of content distribution. To address this issue, in the article, we propose an approach of the content distribution scheme based on Fuzzy Logic and Coalition Graph Games. Specifically, first, the fuzzy logic is used to calculate the vehicle's ability as a relay vehicle within the RSU communication range, and according to the density of the vehicle to determine the proportion of the selected relay vehicle. Then, we divided the road into sections, established alliance according to user similarity index and applied the coalition game theory in every block for content distribution. Extensive simulations validate that the proposed scheme show good performance in terms of reducing latency, energy consumption and expanding the distribution range of content. [ABSTRACT FROM AUTHOR]

In August 2021, the US Food and Drug Administration approved Nexviazyme (avalglucosidase alfa-ngpt) for intravenous infusion to treat patients 1 year of age and older with late-onset Pompe disease (LOPD). The effectiveness and safety were studied in patients with LOPD and patients with infantile-onset Pompe disease (IOPD). The dosage(s) tested in clinical trials was 20 mg/kg every other week (qow) in patients with LOPD and 20 mg/kg and 40 mg/kg qow in patients with IOPD. While patients 3 years old and greater with LOPD were eligible for participation in the pivotal trial, the youngest patient enrolled was 16 years old. Therefore, pediatric patients with LOPD were not well represented in the clinical trial. The prevalence of LOPD in pediatrics is extremely low. Thus, conducting a clinical trial in pediatric patients with LOPD would be challenging. Given the similar pathophysiology, mechanism of action, and disease manifestations across the age spectrum of patients with LOPD, the approved dosages for pediatric patients younger than 16 years old with LOPD were based on extrapolation of efficacy using a model-informed exposure bridging strategy, leveraging the safety data from pediatric patients with IOPD. Specifically, the exposure associated with 20 mg/kg qow in adult patients with LOPD was the target exposure for bridging of efficacy. The safety data obtained with 40 mg/kg qow in patients with IOPD was leveraged to support approval in pediatric patients with LOPD aged 1 year and older. This article illustrates a regulatory use of model-informed extrapolation approach for dose selection in pediatric patients with a rare disease. [ABSTRACT FROM AUTHOR]

Aims: Plant-plant interactions are determined by resource availability. However, its responses to differences in soil phosphorus (P) and water and the rhizospheric driving mechanism have not been systematically revealed. Methods: A pot-culture experiment was conducted in monoculture and in mixture with maize and grass pea. Resource stress treatments were created by organic and inorganic P applications (phytate and KH2PO4) as well as drought and well-watered treatments to address the above issue. Results: Intercropping increased system yield and biomass by 3.5% and 4.5% on average in soils with sufficient P and water, and by 12.0% and 11.7% under stressful conditions respectively. With increasing water and P availability, the yield-based interaction types transited from mutually facilitated to maize facilitated with grass pea as facilitator. Comparatively, the biomass-based facilitation shifting from maize facilitated and grass pea neutral to both being facilitated with increasing stress. This shift was probably mediated by complementary use of soil water in the two species, and rhizospheric acidification in grass pea. Also, rhizospheric interactions promoted phosphatase secretion by 5.3–22.2%, and mobilized organic P to buffer P limitation under P-deficient soils. Regardless of crop species, reproductive and vegetative biomass fell into a typical allometric pattern (α > 1). The rhizospheric interactions drove the differentiated biomass allocation patterns and the species-specific interaction transition. Conclusion: High P and water environments intensified the asymmetric interspecific competition. The trait-dependent facilitation shift was mechanically driven by rhizospheric interaction in intercropping systems. The findings update the understanding on stress gradient hypothesis in a modified model. [ABSTRACT FROM AUTHOR]

Acquired resistance to systemic treatments is inevitable in most cancers, but the genetic basis for this in many cancer types has remained elusive due to constraints in obtaining tissue specimens longitudinally. In the management of gastrointestinal cancers, molecular profiling is conventionally performed at a single time point, although serial evaluations may yield biological insights that inform treatment decisions. We characterize genetic changes in serial liquid biopsies which provide real-time snapshots of tumor genetics and heterogeneity in refractory non-colorectal gastrointestinal cancers, and determine the clinical utility of repeat circulating tumor DNA (ctDNA) testing. In a national cohort of 449 patients with pancreatic, biliary, esophagogastric, and hepatocellular cancers, resistance to conventional therapies is broadly associated with tumor evolution. Emergent ctDNA alterations only detectable at progression occurs in 63% of patients and are frequently associated with treatment actionability. Tumor mutation burden is dynamic in cancers undergoing treatment, but is not associated with time to progression. Objective tumor responses in a case series of patients receiving treatment matched to emergent alterations show that repeat liquid biopsies may have clinical benefit by expanding treatment options in advanced gastrointestinal cancers. Acquired resistance can be associated with genetic changes, however, clinical molecular profiling is usually only considered at the time of diagnosis. Here, the authors use serial ctDNA profiling of 449 gastrointestinal cancers to demonstrate widespread tumour evolution associated with treatment resistance and its potential implications for treatment. [ABSTRACT FROM AUTHOR]

In this paper, we study the number of traveling wave families near a shear flow under the influence of Coriolis force, where the traveling speeds lie outside the range of the flow u. Under the β -plane approximation, if the flow u has a critical point at which u attains its minimal (resp. maximal) value, then a unique transitional β value exists in the positive (resp. negative) half-line such that the number of traveling wave families near the shear flow changes suddenly from finite to infinite when β passes through it. On the other hand, if u has no such critical points, then the number is always finite for positive (resp. negative) β values. This is true for general shear flows under mildly technical assumptions, and for a large class of shear flows including a cosine jet u (y) = 1 + cos (π y) 2 (i.e. the sinus profile) and analytic monotone flows unconditionally. The sudden change of the number of traveling wave families indicates that long time dynamics around the shear flow is much richer than the non-rotating case, where no such traveling wave families exist. [ABSTRACT FROM AUTHOR]

Neuromorphic computing memristors are attractive to construct low-power- consumption electronic textiles due to the intrinsic interwoven architecture and promising applications in wearable electronics. Developing reconfigurable fiber-based memristors is an efficient method to realize electronic textiles that capable of neuromorphic computing function. However, the previously reported artificial synapse and neuron need different materials and configurations, making it difficult to realize multiple functions in a single device. Herein, a textile memristor network of Ag/MoS2/HfAlOx/carbon nanotube with reconfigurable characteristics was reported, which can achieve both nonvolatile synaptic plasticity and volatile neuron functions. In addition, a single reconfigurable memristor can realize integrate-and-fire function, exhibiting significant advantages in reducing the complexity of neuron circuits. The firing energy consumption of fiber-based memristive neuron is 1.9 fJ/spike (femtojoule-level), which is at least three orders of magnitude lower than that of the reported biological and artificial neuron (picojoule-level). The ultralow energy consumption makes it possible to create an electronic neural network that reduces the energy consumption compared to human brain. By integrating the reconfigurable synapse, neuron and heating resistor, a smart textile system is successfully constructed for warm fabric application, providing a unique functional reconfiguration pathway toward the next-generation in-memory computing textile system. Neuromorphic computing memristors are attractive to construct low-power- consumption electronic textiles. Here, authors report an ultralow-power textile memristor network of Ag/MoS2/HfAlOx/carbon nanotube with reconfigurable characteristics and firing energy consumption of 1.9 fJ/spike. [ABSTRACT FROM AUTHOR]