RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo.

Circular RNAs (circRNAs) are a class of single-stranded RNAs with a contiguous structure that have enhanced stability and a lack of end motifs necessary for interaction with various cellular proteins. Here, we show that unmodified exogenous circRNA is able to bypass cellular RNA sensors and thereby avoid provoking an immune response in RIG-I and Toll-like receptor (TLR) competent cells and in mice. The immunogenicity and protein expression stability of circRNA preparations are found to be dependent on purity, with small amounts of contaminating linear RNA leading to robust cellular immune responses. Unmodified circRNA is less immunogenic than unmodified linear mRNA in vitro, in part due to the evasion of TLR sensing. Finally, we provide the first demonstration to our knowledge of exogenous circRNA delivery and translation in vivo, and we show that circRNA translation is extended in adipose tissue in comparison to unmodified and uridine-modified linear mRNAs.

Defence and nutrition synergistically contribute to the distinct tolerance of rice subspecies to the stem borer, Chilo suppressalis.

Damage caused by the rice striped stem borer (SSB), Chilo suppressalis (Walker) (Lepidoptera: Pyralidae), is much more severe on indica/xian rice than on japonica/geng rice (Oryza sativa) which matches pest outbreak data in cropping regions of China. The mechanistic basis of this difference among rice subspecies remains unclear. Using transcriptomic, metabolomic and genetic analyses in combination with insect bioassay experiments, we showed that japonica and indica rice utilise different defence responses to repel SSB, and that SSB exploited plant nutrition deficiencies in different ways in the subspecies. The more resistant japonica rice induced patterns of accumulation of methyl jasmonate (MeJA-part of a defensive pathway) and vitamin B1 (VB1-a nutrition pathway) distinct from indica cultivars. Using gene-edited rice plants and SSB bioassays, we found that MeJA and VB1 jointly affected the performance of SSB by disrupting juvenile hormone levels. In addition, genetic variants of key biosynthesis genes in the MeJA and VB1 pathways (OsJMT and OsTH1, respectively) differed between japonica and indica rice and contributed to performance differences; in indica rice, SSB avoided the MeJA defence pathway and hijacked the VB1 nutrition-related pathway to promote development. The findings highlight important genetic and mechanistic differences between rice subspecies affecting SSB damage which could be exploited in plant breeding for resistance.

Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters.

BACKGROUND: There is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. OBJECTIVES: This study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. METHODS: In experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. RESULTS: In experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2-0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. CONCLUSIONS: The optimal dietary Se dose for reproductive health of breeder roosters is 0.25-0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

HPV positivity status in males is related to the acquisition of HPV infection in females in heterosexual couples.

PURPOSE: Few studies have focused on the impact of human papillomavirus (HPV) positivity in male partners on female HPV infection and cervical lesions. The purpose of this study was to evaluate the impact of the HPV infection status of husbands on wives' cervical HPV infection and lesions. METHODS: We surveyed 251 monogamous couples who attended the outpatient department of Fujian Maternity and Child Health Hospital from 2013 to 2021. HPV type analysis was performed on exfoliated cells of the females' cervix and males' urethra by the PCR-reverse dot blot method. We analyzed the prevalence and consistency of HPV types in 251 couples. Subsequently, the risk of HPV infection in females with HPV-positive male partners was analyzed. SPSS version 26 (IBM, Chicago, USA) was used for statistical analysis. RESULTS: In 251 couples, the most commonly detected high-risk HPV (HR-HPV) genotypes were 52, 51, 16, and 58 for males and 16, 52, 18, and 58 for females. Wives with HPV-positive husbands had higher infection rates for most HR-HPV genotypes. HR-HPV positivity in husbands was a risk factor for the development of cervical lesions in wives (OR = 2.250, P = 0.014). Both single-type (OR = 2.085, P = 0.040) and multiple-type (OR = 2.751, P = 0.036) infection in husbands will contributed to an increased risk of non-HR-HPV infection and cervical lesions in wives. CONCLUSION: Husbands' HPV positivity increases the burden of non-HR-HPV infection and increases the risk of cervical lesions developing in wives. It is hoped to provide a reference value for cervical cancer prevention in females and HPV vaccination in males.

Mobility of Condensed Counterions in Ion-Exchange Membranes: Application of Screening Length Scaling Relationship in Highly Charged Environments.

Ion-exchange membranes (IEMs) are widely used in water, energy, and environmental applications, but transport models to accurately simulate ion permeation are currently lacking. This study presents a theoretical framework to predict ionic conductivity of IEMs by introducing an analytical model for condensed counterion mobility to the Donnan-Manning model. Modeling of condensed counterion mobility is enabled by the novel utilization of a scaling relationship to describe screening lengths in the densely charged IEM matrices, which overcame the obstacle of traditional electrolyte chemistry theories breaking down at very high ionic strength environments. Ionic conductivities of commercial IEMs were experimentally characterized in different electrolyte solutions containing a range of mono-, di-, and trivalent counterions. Because the current Donnan-Manning model neglects the mobility of condensed counterions, it is inadequate for modeling ion transport and significantly underestimated membrane conductivities (by up to ≈5× difference between observed and modeled values). Using the new model to account for condensed counterion mobilities substantially improved the accuracy of predicting IEM conductivities in monovalent counterions (to as small as within 7% of experimental values), without any adjustable parameters. Further adjusting the power law exponent of the screen length scaling relationship yielded reasonable precision for membrane conductivities in multivalent counterions. Analysis reveals that counterions are significantly more mobile in the condensed phase than in the uncondensed phase because electrostatic interactions accelerate condensed counterions but retard uncondensed counterions. Condensed counterions still have lower mobilities than ions in bulk solutions due to impedance from spatial effects. The transport framework presented here can model ion migration a priori with adequate accuracy. The findings provide insights into the underlying phenomena governing ion transport in IEMs to facilitate the rational development of more selective membranes.

Efficient Multi-Sound Source Localization Algorithm for Transformer Faults Based on Polyphase Filters.

Power transformers play a critical role in power systems, and the early detection of their faults and defects, accounting for over 30%, can be achieved through abnormal sound analysis. Sound source localization based on microphone arrays has proven effective in focusing on the troubleshooting scope, preventing potential severe hazards caused by delays in fault removal, and significantly reducing operational and maintenance difficulties and costs. However, existing microphone array-based sound source localization algorithms face challenges in maintaining both accuracy and simplicity and especially suffer from a sharp decrease in performance when dealing with multiple sound sources. This paper presents a multi-sound source localization algorithm for transformer faults based on polyphase filters, integrating the sum-difference monopulse angle measurement technique into the microphone array. Firstly, the signals received from the transformers are divided into multiple subbands using polyphase filters, allowing for multi-source separation and reducing the sampling rate of each subband. Next, the time-domain signals in subbands subject to noise suppression are processed into sum and difference beams. The resulting beam outputs are transformed into frequency-domain signals using the Fast Fourier Transform (FFT), effectively enhancing the signal-to-noise ratio (SNR) for separate sound sources. Finally, each subband undergoes sum-difference monopulse angle measurement in the frequency domain to achieve the high-precision localization of specific faults. The proposed algorithm has been demonstrated to be effective in achieving higher localization accuracy and reducing computational complexity in the presence of actual amplitude-phase errors in microphone arrays. These advantages can facilitate its practical applications. By enabling early targeting of fault sources when abnormalities occur, this algorithm provides valuable assistance to operation and maintenance personnel, thereby enhancing the maintenance efficiency of transformers.

Effects of Sapindus mukorossi Seed Oil on Bone Healing Efficiency: An Animal Study.

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.

Selenium Deficiency Dysregulates One-Carbon Metabolism in Nutritional Muscular Dystrophy of Chicks.

BACKGROUND: Nutritional muscular dystrophy (NMD) in animals is induced by dietary selenium (Se) deficiency. OBJECTIVES: This study was conducted to explore the underlying mechanism of Se deficiency-induced NMD in broilers. METHODS: One-day-old male Cobb broilers (n = 6 cages/diet, 6 birds/cage) were fed a Se-deficient diet (Se-Def, 47 µg Se/kg) or the Se-Def supplemented with 0.3 mg Se/kg (control) for 6 wk. Thigh muscles of broilers were collected at week 6 for measuring Se concentration, histopathology, and transcriptome and metabolome assays. The transcriptome and metabolome data were analyzed with bioinformatics tools and other data were analyzed with Student's t tests. RESULTS: Compared with the control, Se-Def induced NMD in broilers, including reduced (P < 0.05) final body weight (30.7%) and thigh muscle size, reduced number and cross-sectional area of fibers, and loose organization of muscle fibers. Compared with the control, Se-Def decreased (P < 0.05) the Se concentration in the thigh muscle by 52.4%. It also downregulated (P < 0.05) GPX1, SELENOW, TXNRD1-3, DIO1, SELENOF, H, I, K, M, and U by 23.4-80.3% in the thigh muscle compared with the control. Multi-omics analyses indicated that the levels of 320 transcripts and 33 metabolites were significantly altered (P < 0.05) in response to dietary Se deficiency. Integrated transcriptomics and metabolomics analysis revealed that one-carbon metabolism, including the folate and methionine cycle, was primarily dysregulated by Se deficiency in the thigh muscles of broilers. CONCLUSIONS: Dietary Se deficiency induced NMD in broiler chicks, potentially with the dysregulation of one-carbon metabolism. These findings may provide novel treatment strategies for muscle disease.

Heat Stress Impairs Male Reproductive System with Potential Disruption of Retinol Metabolism and Microbial Balance in the Testis of Mice.

BACKGROUND: Heat stress (HS) has a harmful impact on the male reproductive system, primarily by reducing the sperm quality. The testicular microenvironment plays an important role in sperm quality. OBJECTIVES: This study aimed to explore the underlying mechanism by which HS impairs the male reproductive system through the testicular microenvironment. METHODS: Ten-week-old male mice (n = 8 mice/group) were maintained at a normal temperature (25°C, control) or subjected to HS (38°C for 2 h each day, HS) for 2 wk. The epididymides and testes were collected at week 2 to determine sperm quality, histopathology, retinol concentration, the expression of retinol metabolism-related genes, and the testicular microbiome. The testicular microbiome profiles were analyzed using biostatistics and bioinformatics; other data were analyzed using a 2-sided Student's t test. RESULTS: Compared with the control, HS reduced (P < 0.05) sperm count (42.4%) and motility (97.7%) and disrupted the integrity of the blood-testis barrier. Testicular microbial profiling analysis revealed that HS increased the abundance of the genera Asticcacaulis, Enhydrobacter, and Stenotrophomonas (P < 0.05) and decreased the abundance of the genera Enterococcus and Pleomorphomonas (P < 0.05). Notably, the abundance of Asticcacaulis spp. showed a significant negative correlation with sperm count (P < 0.001) and sperm motility (P < 0.001). Moreover, Asticcacaulis spp. correlated significantly with most blood differential metabolites, particularly retinol (P < 0.05). Compared with the control, HS increased serum retinol concentrations (25.3%) but decreased the testis retinol concentration by 23.7%. Meanwhile, HS downregulated (P < 0.05) the expression of 2 genes (STRA6 and RDH10) and a protein (RDH10) involved in retinol metabolism by 27.3%-36.6% in the testis compared with the control. CONCLUSIONS: HS reduced sperm quality, mainly because of an imbalance in the testicular microenvironment potentially caused by an increase in Asticcacaulis spp. and disturbed retinol metabolism. These findings may offer new strategies for improving male reproductive capacity under HS.

The fibrous character of pericellular matrix mediates cell mechanotransduction.

Cells in solid tissues sense and respond to mechanical signals that are transmitted through extracellular matrix (ECM) over distances that are many times their size. This long-range force transmission is known to arise from strain-stiffening and buckling in the collagen fiber ECM network, but must also pass through the denser pericellular matrix (PCM) that cells form by secreting and compacting nearby collagen. However, the role of the PCM in the transmission of mechanical signals is still unclear. We therefore studied an idealized computational model of cells embedded within fibrous collagen ECM and PCM. Our results suggest that the smaller network pore sizes associated with PCM attenuates tension-driven collagen-fiber alignment, undermining long-range force transmission and shielding cells from mechanical stress. However, elongation of the cell body or anisotropic cell contraction can compensate for these effects to enable long distance force transmission. Results are consistent with recent experiments that highlight an effect of PCM on shielding cells from high stresses. Results have implications for the transmission of mechanical signaling in development, wound healing, and fibrosis.

T-2 toxin-induced intestinal damage with dysregulation of metabolism, redox homeostasis, inflammation, and apoptosis in chicks.

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.

Genomic signatures and evolutionary history of the endangered blue-crowned laughingthrush and other Garrulax species.

BACKGROUND: The blue-crowned laughingthrush (Garrulax courtoisi) is a critically endangered songbird endemic to Wuyuan, China, with population of ~323 individuals. It has attracted widespread attention, but the lack of a published genome has limited research and species protection. RESULTS: We report two laughingthrush genome assemblies and reveal the taxonomic status of laughingthrush species among 25 common avian species according to the comparative genomic analysis. The blue-crowned laughingthrush, black-throated laughingthrush, masked laughingthrush, white-browed laughingthrush, and rusty laughingthrush showed a close genetic relationship, and they diverged from a common ancestor between ~2.81 and 12.31 million years ago estimated by the population structure and divergence analysis using 66 whole-genome sequencing birds from eight laughingthrush species and one out group (Cyanopica cyanus). Population inference revealed that the laughingthrush species experienced a rapid population decline during the last ice age and a serious bottleneck caused by a cold wave during the Chinese Song Dynasty (960-1279 AD). The blue-crowned laughingthrush is still in a bottleneck, which may be the result of a cold wave together with human exploitation. Interestingly, the existing blue-crowned laughingthrush exhibits extremely rich genetic diversity compared to other laughingthrushes. These genetic characteristics and demographic inference patterns suggest a genetic heritage of population abundance in the blue-crowned laughingthrush. The results also suggest that fewer deleterious mutations in the blue-crowned laughingthrush genomes have allowed them to thrive even with a small population size. We believe that cooperative breeding behavior and a long reproduction period may enable the blue-crowned laughingthrush to maintain genetic diversity and avoid inbreeding depression. We identified 43 short tandem repeats that can be used as markers to identify the sex of the blue-crowned laughingthrush and aid in its genetic conservation. CONCLUSIONS: This study supplies the missing reference genome of laughingthrush, provides insight into the genetic variability, evolutionary potential, and molecular ecology of laughingthrush and provides a genomic resource for future research and conservation.

Comparison of interaction, structure, and cell proliferation of α-lactalbumin-safflower yellow complex induced by microwave heating or conventional heating.

BACKGROUND: The protein-polyphenol interaction mechanism has always been a research hotspot, but their interaction is affected by heat treatment, which is widely applied in food processing. Moreover, the effects of microwave or water-bath heating on the protein-polyphenol interaction mechanism have been not clarified. The pasteurization condition (65 °C, 30 min) was selected to compare the effects of microwave or water bath on binding behavior, structure, and cell proliferation between α-lactalbumin (α-LA) and safflower yellow (SY), thus providing a guide for the selection of functional dairy processing conditions. RESULTS: Microwave heat treatment of α-LA-SY resulted in stronger fluorescence quenching than that of conventional heat treatment. Moreover, the binding constant Ka of all α-LA-SY samples was augmented significantly after microwave or water bath treatment, and microwave-heated α-LA-SY showed the maximum Ka . Fourier transform infrared spectroscopy showed that microwave heating resulted in more ordered structures of α-LA into its disordered structures than water bath heating. However, the ferric reducing antioxidant power and chroma value of α-LA-SY were more reduced by microwave heating than by water bath heating. Moreover, microwave heating facilitated the cell proliferation of α-LA-SY compared with water bath treatment. CONCLUSION: It was demonstrated that microwave heating promoted interaction between α-LA and SY more than water bath heating did. Microwave heat treatment was a safe and effective way to enhance the binding affinity of α-LA to SY, being a potential application in food industry. © 2022 Society of Chemical Industry.

Structural and Dynamic Disorder, Not Ionic Trapping, Controls Charge Transport in Highly Doped Conducting Polymers.

Doped organic semiconductors are critical to emerging device applications, including thermoelectrics, bioelectronics, and neuromorphic computing devices. It is commonly assumed that low conductivities in these materials result primarily from charge trapping by the Coulomb potentials of the dopant counterions. Here, we present a combined experimental and theoretical study rebutting this belief. Using a newly developed doping technique based on ion exchange, we prepare highly doped films with several counterions of varying size and shape and characterize their carrier density, electrical conductivity, and paracrystalline disorder. In this uniquely large data set composed of several classes of high-mobility conjugated polymers, each doped with at least five different ions, we find electrical conductivity to be strongly correlated with paracrystalline disorder but poorly correlated with ionic size, suggesting that Coulomb traps do not limit transport. A general model for interacting electrons in highly doped polymers is proposed and carefully parametrized against atomistic calculations, enabling the calculation of electrical conductivity within the framework of transient localization theory. Theoretical calculations are in excellent agreement with experimental data, providing insights into the disorder-limited nature of charge transport and suggesting new strategies to further improve conductivities.

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF-κB/C-myc.

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR-HPV infection and high-grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF-κB, C-myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR-HPV infection-related cervical lesions through host NF-κB and C-myc signaling.

Effects of tendon viscoelasticity on the distribution of forces across sutures in a model tendon-to-bone repair.

Tears to the rotator cuff often require surgical repair. These repairs often culminate in re-tearing when sutures break through the tendon in the weeks following repair. Although numerous studies have been performed to identify suturing strategies that reduce this risk by balancing forces across sutures, none have accounted for how the viscoelastic nature of tendon influences load sharing. With the aim of providing insight into this problem, we studied how tendon viscoelasticity, tendon stiffness, and suture anchor spacing affect this balancing of forces across sutures. Results from a model of a three-row sutured re-attachment demonstrated that optimized distributions of suture stiffnesses and of the spacing of suture anchors can balance the forces across sutures to within a few percent, even when accounting for tendon viscoelasticity. Non-optimized distributions resulted in concentrated force, typically in the outermost sutures. Results underscore the importance of accounting for viscoelastic effects in the design of tendon to bone repairs.

Night sky brightness monitoring network in Wuxi, China.

The rapid development of cities has brought tremendous pressure to astronomical observation, energy security, and the ecosystem. Automatic monitoring of night sky brightness (NSB) can help us to understand its regional differences and time variations of NSB effectively and to investigate the human and natural factors which lead to these changes. In this paper, the construction of Wuxi City night sky brightness monitoring network (WBMN) in China is presented. In addition to introducing the equipment and the installation of the network, a brief analysis of the data obtained from the stations will also be presented. The impact of human activities on the NSB is illustrated through its changes during the Spring Festival (lunar new year) and non-festival nights, and through a comparison study between NSB data taken from locations of different land usages. It is concluded that, while the reduction in human activities after non-festival midnights or the reduction in moon illumination near the new moon epoch led to darker night skies, brightening of the night skies may be attributed to firework displays during the nights of Spring Festival in 2019. On the other hand, the absence of firework during the Spring Festival in 2020 may explain the darker night skies. Finally, there is an evidence that the urban developments in Wuxi are degrading night sky quality.

SAVSDN: A Scene-Aware Video Spark Detection Network for Aero Engine Intelligent Test.

Due to carbon deposits, lean flames, or damaged metal parts, sparks can occur in aero engine chambers. At present, the detection of such sparks deeply depends on laborious manual work. Considering that interference has the same features as sparks, almost all existing object detectors cannot replace humans in carrying out high-precision spark detection. In this paper, we propose a scene-aware spark detection network, consisting of an information fusion-based cascading video codec-image object detector structure, which we name SAVSDN. Unlike video object detectors utilizing candidate boxes from adjacent frames to assist in the current prediction, we find that efforts should be made to extract the spatio-temporal features of adjacent frames to reduce over-detection. Visualization experiments show that SAVSDN can learn the difference in spatio-temporal features between sparks and interference. To solve the problem of a lack of aero engine anomalous spark data, we introduce a method to generate simulated spark images based on the Gaussian function. In addition, we publish the first simulated aero engine spark data set, which we name SAES. In our experiments, SAVSDN far outperformed state-of-the-art detection models for spark detection in terms of five metrics.

Brand equity and the Covid-19 stock market crash: Evidence from U.S. listed firms.

Brand equity has played an important role in firms' stock performance, especially during the stock market crash provoked by Covid-19. Our manuscript investigates how brand equity impacts stock performance during the Covid-19 crash. Firms with top brands should be a particularly attractive "safe harbor" in the crash to investors since consumer loyalty and demand advantages brought by brand equity enable firms to retain stable cash flows and mitigate the macroeconomic shock. Based on U.S. listed firms, we find that firms with top brands experience higher stock returns, lower systematic risk and lower idiosyncratic risk in the Covid-19 crash than other firms. Moreover, our findings are used to distinguish the brand equity effect from the corporate social responsibility (CSR) effect on stock performance during the Covid-19 crash.

mRNA Delivery for Therapeutic Anti-HER2 Antibody Expression In Vivo.

Antibody-based drugs are a leading class of biologics used to treat a variety of diseases, including cancer. However, wide antibody implementation is hindered by manufacturing challenges and high production cost. Use of in-vitro-transcribed mRNA (IVT-mRNA) for endogenous protein expression has the potential to circumvent many of the shortcomings of antibody production and therapeutic application. Here, we describe the development of an IVT-mRNA system for in vivo delivery of a humanized anti-HER2 (also known as ERBB2) antibody, trastuzumab, and demonstrate its anticancer activity. We engineered the IVT-mRNA sequence to maximize expression, then formulated the IVT-mRNA into lipid-based nanoparticles (LNPs) to protect the mRNA from degradation and enable efficient in vivo delivery. Systemic delivery of the optimized IVT-mRNA loaded into LNPs resulted in antibody serum concentrations of 45 ± 8.6 µg/mL for 14 days after LNP injection. Further studies demonstrated an improved pharmacokinetic profile of the produced protein compared to injection of trastuzumab protein. Finally, treatment of tumor-bearing mice with trastuzumab IVT-mRNA LNPs selectively reduced the volume of HER2-positive tumors and improved animal survival. Taken together, the results of our study demonstrate that using IVT-mRNA LNPs to express full-size therapeutic antibodies in the liver can provide an effective strategy for cancer treatment and offers an alternative to protein administration.