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Abstract To determine the risk factors for poor prognosis of influenza-associated encephalopathy (IAE), 56 eligible children with IAE who were treated in the pediatric intensive care unit of Wuhan Children’s Hospital from January 2022 to December 2023 were selected for retrospective analysis and grouped according to poor prognosis or not, and independent risk factors for poor prognosis were found by regression analysis. Results showed 26 children (26/30, 46.4%) had a poor prognosis. In the univariate analysis, the poor prognosis group compared with the clinically cured group showed a significant increase in the number of days of hospitalization (3.0 vs. 9.5 days, P

Abstract To develop an atrophic Meibomian Gland Dysfunction (MGD) animal model via liquid nitrogen cryotherapy, the eyelid edges of C57 mice exposure to liquid nitrogen for 30 s. Morphology of MG and ocular surface were assessed using stereomicroscopy and a slit lamp microscope at multiple time points post-injury. Acinar loss and atrophy were observed from day 7, with increased inflammation and apoptosis, and decreased proliferation in acinar cells. Corneal epithelial defects appeared after day 14. Liquid nitrogen induced selective damage to meibomian acinar cells, simulating MGD pathology effectively, with peak effects at day 21, providing a relevant model for atrophic MGD research.

Abstract Evidence suggest that dietary advanced glycation end products (AGEs) might exert harmful effects on female reproductive function. However, population-based studies exploring the associations between dietary AGEs intake and female infertility remain lacking. This studyaimed to determine the relationship between dietary AGEs intake and female infertility based on National Health and Nutrition Examination Survey (NHANES). A cross-sectional analysis of 2863 participants in the NHANES 2013–2018 were included. The dietary AGEs, i.e. Nε-(carboxymethyl)lysine(CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of ultra-performance LC-tandem MS dietary AGEs database and two 24-h dietary recall interviews. Multivariate Logistic regression analyses were adopted to explore the relationships between dietary AGEs intake and self-reported infertility risk. Compared to the lowest tertile, total dietary AGEs (P-trend = 0.089) and CML (P-trend = 0.032) in the upper tertile were positively correlated with female infertility, and the corresponding odds radios (ORs) (95% confidence interval (CI)) were 1.44 (1.01, 2.06) and 1.64 (1.10, 2.45) respectively. Subgroups analysis found that in participants with overweight and obese, each 1-SD increment in dietary AGEs, CML and MG-H1 level was associated with 18% (95% CI: 1-38%), 21% (95% CI: 1-46%), and 16% (95% CI: 0-36%) elevated risk of infertility. Elevated dietary AGEs intake was associated with the higher risk of infertility for female subjects, this positive association was more pronounced in women with excess body weight.

Abstract In the era of the global knowledge economy, the rapid advancement of new-generation information technologies has positioned digital industry at the forefront of socio-economic development. Digital industrial clusters, comprising key enterprises and related institutions, have emerged as global hubs for technological innovation, drawing recognition from governments and international organizations. However, China’s digital industry faces challenges characterized by being “large but not strong” and experiencing “industrial structure softening.” This paper explores the temporal evolution and spatial distribution of China’s digital industry, shedding light on its unique patterns. This study reveals that China’s digital industry has progressed through four distinct phases, evolving from manufacturing-oriented to service-oriented, and experiencing dynamic stability. In terms of spatial distribution, it exhibits a pattern known as the “One Core, Three Poles, and Multiple Strongholds,” with Beijing as the core and Shanghai, Shenzhen, Hangzhou, among others, serving as growth poles. The study identifies factors influencing spatial distribution, including software development, patent authorizations, mobile phone penetration, industrial parks, digital finance, and foreign investment. Manufacturing-based digital industries prioritize innovation and IP protection, while service-based sectors rely on software development, innovation, and international collaboration. The GWR model demonstrates spatial variation, emphasizing the importance of tailored development strategies. This research contributes to understanding the dynamics of China’s digital industry and provides valuable insights for policymakers aiming to create an internationally competitive digital industry cluster.

Abstract In recent years, as river-borne sediment transport has decreased, land loss in estuarine areas has become increasingly severe. Particularly from 2009 to 2022, due to the reduced sediment load from the upper reaches of the Yangtze River, significant changes in the erosion-deposition conditions at the Yangtze River Estuary have become a critical concern. The suspended sediment concentration (SSC) in the estuary is closely linked to sediment content, and against this backdrop, this study aims to thoroughly explore the response mechanisms of the Yangtze River Estuary’s SSC to changes in erosion-deposition conditions, with the goal of providing scientific bases and strategic recommendations for erosion-deposition management. To this end, this research collected historical water depth data for the Yangtze River Estuary, measured vertical distribution of SSC in September 2022, surface suspended sediment concentration (SSSC) data from 2021 to 2023, and 25 factors influencing SSSC, to analyze in detail the changes in the erosion-deposition conditions at the Yangtze River Estuary and the response mechanisms of SSC to these changes. The analysis showed that between 2009 and 2022, the mouth bar area of the Yangtze River Estuary experienced net erosion for the first time since 1958, with an annual erosion rate reaching 63.2 × 10^6 m3/yr, and the highest erosion rate occurring in the North Passage area, reaching 83.3 mm/yr. This phenomenon is likely caused by human-induced changes in underwater topography, with the Yangtze River Estuary shifting from deposition to erosion. Between 2021 and 2023, the turbidity maximum zone (TMZ) of the Yangtze River Estuary did not show regular changes in SSSC, which may be related to the frequent occurrence of typhoons and changes in sediment supply in the submerged delta of the Yangtze River Estuary.

Abstract Machinery operation is a major source of carbon emissions in building deconstruction. Early intervention through Design for Deconstruction (DfD) is crucial for emission reduction, yet the factors influencing these emissions are underexplored. This study integrates parametric BIM with multi-objective optimization (MOO) to assess mechanical carbon emissions in deconstruction. Using the Octopus solver in Grasshopper for Rhino, the study analyzes independent variables—possible working hours (PWH), vertical speed (VS), and horizontal speed (HS)—and dependent variables—minimum mechanical carbon emissions (MCE (min)), minimum deconstruction period (DP (min)), and maximum working efficiency (WE (max)). A lightweight steel roof truss structure is analyzed, comparing real-world deconstruction with optimized DfD schemes. Sensitivity analysis for BIM-MOO optimized results reveal that: (1) Adjusting PWH, VS, and HS significantly affects WE and DP, though with limited impact on carbon emissions; (2) VS influences WE and DP more than HS; (3) Limiting DP is essential for balancing WE, DP, and MCE, with WE adjusted to 20–60% and modifications to PWH and VS achieving balanced management. This study underscores the importance of early design and real-time adjustments for efficient, low-emission deconstruction, supporting the advancement of green building practices.

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

Abstract In order to solve the influence of the complex interaction relationships among subjects on the system solution accuracy and speed of the Multi-Microgrid system under the high penetration rate of new energy. Firstly, the paper establishes the bi-level optimal scheduling Stackelberg game model based on shared energy storage, considering the inter-subject interaction in MMG. Subsequently, based on the four improvement methods of Chaotic Map, Quantum Behavior, Gaussian Distribution, and Nonlinear Control Strategy, the Chaotic Gaussian Quantum Crayfish Optimization Algorithm is proposed to solve the optimization scheduling model. The improved algorithm exhibits superior initial solutions and enhanced search capability. In comparison to the original algorithm, the relative errors of the CGQCOA optimization outcomes are 98%, 20.96%, 98.74% and 16.55%, respectively, enhancing the model-solving accuracy and the speed of convergence to the optimal solution. Finally, the simulation demonstrates that the revenue of Microgrid 1, Microgrid 2, and Microgrid 3 have increased by 0.73%, 1.17%, and 1.04%, respectively. Concurrently, the penalty cost of pollutant emission has decreased by 5.9%, 11.5%, and 12.68%, respectively. Furthermore, the revenue of the shared storage have increased by 1.91%. These findings validate the efficacy of the methodology proposed in enhancing the revenue of the various subjects and reducing pollutant gas emission.

Abstract Obesity has become a global health problem. In recent years, the influence of dietary microbes in the obese population has attracted the attention of scholars. Our study aimed to investigate the link between live microbe intake and obesity in adults. Participants (aged over 20 years) for this study were from the 1999–2018 National Health and Nutrition Examination Survey (NHANES). Participants were categorised into low, medium and high dietary live microbe intake groups. Linear regression was used to analyse the link between live microbe intake and body mass index (BMI) and waist circumference (WC). Logistic regression was used to analyse the link between live microbe intake and obesity and abdominal obesity prevalence. Restricted cubic spline curves (RCS) were used to check whether there was a non-linear relationship between live microbe intake and obesity. A total of 42,749 participants were included in this study and the number of obese reached 15,463. We found that live microbe intake was negatively linked to BMI and WC. In models adjusted for all confounders, the high live microbe intake group had lower obesity (OR = 0.812, 95%CI: 0.754–0.873) and abdominal obesity prevalence (OR = 0.851, 95%CI: 0.785–0.923) than the lowest intake group. Upon further quantification of live microbe intake, we found similar results. RCS analyses showed that live microbe intake was nonlinearly negatively correlated with BMI, WC, obesity, and abdominal obesity prevalence (P for non-linearity

Abstract Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.

Abstract Post-discharge coping difficulty presents a significant challenge for mothers of preterm infants. The readiness for hospital discharge and parenting self-efficacy are crucial factors influencing post-discharge coping difficulty. However, the pathways through which these factors impact post-discharge coping difficulty remain unclear. This study aims to investigate the impact of readiness for hospital discharge on post-discharge coping difficulty and the mediating role of parenting self-efficacy among mothers of preterm infants. A prospective study involving 462 mothers of preterm infants from six tertiary hospitals in Shandong Province was conducted. Mothers were evaluated on the day of discharge (using the Baseline characteristics and Readiness for Hospital Discharge Scale) and three weeks post-discharge (utilizing the Parenting Sense of Competence Scale-Efficacy subscale and Post-Discharge Coping Difficulty Scale). Structural equation modeling was employed to analyze the mediating effect. The results of this study revealed that readiness for hospital discharge significantly decreased post-discharge coping difficulty (β = − 0.533, P

Abstract Feeding behavior, the most fundamental physiological activity, is controlled by two opposing groups of factors, orexigenic and anorexigenic factors. The sulfakinin family, an insect analogue of the mammalian satiety factor cholecystokinin (CCK), has been shown to suppress food intake in various insects. Nevertheless, the mechanisms through which sulfakinin regulates feeding behavior remain a biological question. This study aimed to elucidate the signaling pathway mediated by the anorexigenic peptide sulfakinin in Bombyx mori. We identified the Bombyx mori neuropeptide G protein-coupled receptor A9 (BNGR-A9) as the receptor for sulfakinin through functional assays. Stimulation with sulfakinin triggered a swift increase in intracellular IP3, Ca2+, and a notable enhancement of ERK1/2 phosphorylation, in a manner sensitive to a Gαq-specific inhibitor. Treatment with synthetic sulfakinin resulted in decreased food consumption and average body weight. Additionally, administering synthetic sulfakinin to silkworms significantly elevated hemolymph trehalose levels, an effect markedly reduced by pre-treatment with BNGR-A9 dsRNA. Consequently, our findings establish the sulfakinin/BNGR-A9 signaling pathway as a critical regulator of feeding behavior and hemolymph trehalose homeostasis in Bombyx mori, highlighting its roles in the negative control of food intake and the positive regulation of energy balance.

Abstract The purpose of this study is to evaluate loose suture-related inflammation and activation of conjunctiva-associated lymphoid tissue (CALT) in patients after keratoplasty. The patients who were treated with keratoplasty at the First Affiliated Hospital of Harbin Medical University between 2015 and 2022 were recruited into the study. We evaluated the time and location of loose suture development in patients after keratoplasty. In addition, in vivo confocal microscopy was used to evaluate the activation of CALT and the accumulation of inflammatory cells around loose sutures. Meso Scale Discovery assay detection kits were used to evaluate the inflammatory cytokines in the tears of patients before and after the loose suture was removed. In this study, we collected the information from 212 cases (212 eyes) who had PK (126 eyes) and DALK-treated (86 eyes) for corneal transplantation, including 124 males and 88 females, aged 14–84 years old. The average age was 50.65 ± 16.81 years old. Corneal sutures were more prone to loose at 3 months and 6 months after keratoplasty, and the frequent sites were at 5 and 6 o’clock. An increased number of inflammatory cells could be observed around the loose sutures than normal sutures (P

Abstract Simulated moving bed (SMB) technology is considered one of the most successful techniques in chromatographic separation. However, due to the nonlinearity caused by discrete events and sensitivity to numerous separation performance parameters, purity control in SMB systems has been a challenging issue. Fuzzy controllers are increasingly popular in industrial environments due to their simplicity and effectiveness in handling nonlinearity. However, traditional fuzzy controllers used in industry often overlook considerations of error acceleration, resulting in slight deviations from target values under steady-state conditions and oscillatory behavior when system parameters change. This study proposes an advanced fuzzy controller, where in a series of experiments, the purity control targets for component B are set at 94% and 96%, and for component A are set at 96% and 96%, respectively. Experimental results indicate that the advanced fuzzy controller achieves higher precision, with an average deviation of around 0.1%, for both components B and A. Importantly, under variations in adsorbent parameter(from 0.01 to 0.03), feed concentration(from 4.5 to 5.2), and switching time(from 178 to 182), the experimental results demonstrate smoother control with the advanced controller, particularly when oscillations occur with conventional fuzzy controllers due to switching time variations, indicating robust control with the advanced fuzzy controller.

Abstract Global greenhouse gas emission, major factor driving climate change, has been increasing since nineteenth century. STIRPAT and CEVSA models were performed to estimate the carbon emission peaks and terrestrial ecosystem carbon sinks at the provincial level in China, respectively. Utilizing the growth characteristics and the peak time criteria for the period 1997–2019, the patterns of energy consumption and CO2 emissions from 30 Chinese provinces are categorized into four groups: (i) one-stage increase (5 provinces), (ii) two-stage increase (10 provinces), (iii) maximum around 2013 (13 provinces), and (iv) maximum around 2017 (2 provinces). According to the STIRPAT model, the anticipated time of peak CO2 emissions for Beijing from the third group is ~ 2025 in both business-as-usual and high-speed scenarios. For Xinjiang Uygur autonomous region from the first group and Zhejiang province from the second group, the expected peak time is 2025 to 2030. Shaanxi province from the fourth group is likely to reach carbon emission peak before 2030. The inventory-based estimate of China’s terrestrial carbon sink is ~ 266.2 Tg C/a during the period 1982–2015, offsetting 18.3% of contemporary CO2 emissions. The province-level CO2 emissions, peak emissions and terrestrial carbon sinks estimates presented here are significant for those concerned with carbon neutrality.

Abstract The increasing number of plant mitochondrial DNA genomes (mtDNA) sequenced reveals the extent of transfer from both chloroplast DNA genomes (cpDNA) and nuclear DNA genomes (nDNA). This study created a library and assembled the chloroplast and mitochondrial genomes of the leafy sweet potato better to understand the extent of mitochondrial and chloroplast gene transfer. The full-length chloroplast genome of the leafy sweet potato (OM808940) is 161,387 bp, with 132 genes annotated, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The mitochondrial genome (OM808941) was 269,578 bp in length and contained 69 functional genes, including 39 protein-coding genes, 6 rRNA genes, and 24 tRNA genes. 68 SSR loci were found in the leafy sweet potato organelle genome, including 54 in the chloroplast genome and 14 in the mitochondria genome. In the sweet potato mitochondrial genome, most genes have RNA editing sites, and the conversion ratio from hydrophilic amino acids to hydrophobic amino acids is the highest, reaching 47.12%. Horizontal transfer occurs in the sweet potato organelle genome and nuclear genome. 40 mitochondrial genome segments share high homology with 14 chloroplast genome segments, 33 of which may be derived from chloroplast genome horizontal transfer. 171 mitochondrial genome sequences come from the horizontal transfer of nuclear genome. The phylogenetic analysis of organelle genes revealed that the leafy sweet potato was closely related to the tetraploid wild species Ipomoea tabascana and the wild diploid species Ipomoea trifida.

Abstract The purpose of this study is to compare the accuracy and effectiveness of ultrasound-guided and fluoroscopy-guided lumbar selective nerve root block (SNRB), and to explore the feasibility of ultrasound-guided methods. This retrospective study included patients with lumbar radicular pain who underwent ultrasound-guided and fluoroscopy-guided selective nerve root block at Honghui Hospital Affiliated to Xi’an Jiaotong University from August 2020 to August 2022. Patients were divided into U-SNRB group and F-SNRB group according to ultrasound-guided or fluoroscopy-guided selective nerve root block. There were 43 patients in U-SNRB group and 20 patients in F-SNRB group. The pain visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, related indexes and complications were recorded and compared between the two groups before, 30 min, 1 month and 6 months after block. To evaluate the feasibility, accuracy and effectiveness of ultrasound-guided selective nerve root block. There were no complications in the process of selective nerve root block in both groups. The operating time and the times of closing needle angle adjustment in U-SNRB group were better than those in F-SNRB group, and the difference was statistically significant (P 0.05). The accuracy of ultrasound-guided selective nerve root block and the degree of pain relief of patients were similar to those of fluoroscopy guidance, but the operation time and needle angle adjustment times were significantly less than that of fluoroscopy, and could effectively reduce radiation exposure. Therefore, it can be used as a better way to guide for choice.

Abstract Vehicle speed, road roughness grade and sprung mass are the three main factors to influence suspension control and state estimation. Aiming at the problem that fixed state observer cannot guarantee the estimation accuracy of suspension with driving scenario changes, a suspension state observer based on interactive multiple model adaptive Kalman filter (IMMAKF) is established. Firstly, an adaptive control suspension is proposed based on LQR algorithm and multi-objective optimization algorithm, which can automatically adjust the controller parameters according to the vehicle speed, road roughness grade and sprung acceleration parameters, so as to keep the optimal control effect of the suspension. Secondly, the theoretical model of IMMAKF is derived, and two kinds of IMMAKF suspension state observers and controllers are established. Finally, a simulation condition with the vehicle speed, road roughness grade and sprung mass changing simultaneously is established. The simulation results shows that: compared with ordinary IMMKF, AKF and KF observers, the estimation accuracy of IMMAKF5 is improved. Except for state observation, IMMAKF can be used to identify the road roughness grade and estimate the suspension sprung mass.

Abstract Colorectal cancer is a leading cause of cancer-related deaths globally. In recent years, the use of convolutional neural networks in computer-aided diagnosis (CAD) has facilitated simpler detection of early lesions like polyps during real-time colonoscopy. However, the majority of existing techniques require a large training dataset annotated by experienced experts. To alleviate the laborious task of image annotation and utilize the vast amounts of readily available unlabeled colonoscopy data to further improve the polyp detection ability, this study proposed a novel self-supervised representation learning method called feature pyramid siamese networks (FPSiam). First, a feature pyramid encoder module was proposed to effectively extract and fuse both local and global feature representations among colonoscopic images, which is important for dense prediction tasks like polyp detection. Next, a self-supervised visual feature representation containing the general feature of colonoscopic images is learned by the siamese networks. Finally, the feature representation will be transferred to the downstream colorectal polyp detection task. A total of 103 videos (861,400 frames), 100 videos (24,789 frames), and 60 videos (15,397 frames) in the LDPolypVideo dataset are used to pre-train, train, and test the performance of the proposed FPSiam and its counterparts, respectively. The experimental results have illustrated that our FPSiam approach obtains the optimal capability, which is better than that of other state-of-the-art self-supervised learning methods and is also higher than the method based on transfer learning by 2.3 mAP and 3.6 mAP for two typical detectors. In conclusion, FPSiam provides a cost-efficient solution for developing colorectal polyp detection systems, especially in conditions where only a small fraction of the dataset is labeled while the majority remains unlabeled. Besides, it also brings fresh perspectives into other endoscopic image analysis tasks.

Abstract The present study investigated the composition, abundance, and diversity of gut microbes in full-term and late-preterm infants from a medical center in eastern China. A total of 144 genomes of stool samples were captured for 16S rRNA metagenomic analyses. A high abundance of commensal intestinal bacteria was detected in these samples such as Phocaeicola vulgatus, Escherichia coli, and Faecalibacterium prausnitzii, indicating a relatively consistent diversity of gut microbes in the present full-term infants aged 38–40 weeks. However, late preterm infants (n = 50) with mandatory antimicrobials feeding exhibited lower diversity but a higher composition of opportunistic pathogens such as Enterococcus species. Centralized on the situation, we explored the regulatory effect of Clostridium butyricum as probiotics on these late preterm infants. The consumption of C. butyricum did not restore the composition of gut microbes altered by antimicrobials to normal levels, although several opportunistic pathogens decreased significantly after probiotic therapy including Staphylococcus aureus, Sphingomonas echinoides, and Pseudomonas putida. We also compared the effects of day-fed versus night-fed probiotics. Intriguingly, the nighttime feeding showed a higher proportion of C. butyricum compared with probiotic day-feeding. Finally, fecal metabolome and metabolites were analyzed in late preterm infants with (n = 20) or without probiotic therapy (n = 20). The KEGG enrichment analysis demonstrated that vitamin digestion and absorption, synaptic vesicle cycle, and biotin metabolism were significantly increased in the probiotic-treated group, while MSEA indicated that a series of metabolism were significantly enriched in probiotic-treated infants including glycerolipid, biotin, and lysine, indicating the complex effects of probiotic therapy on glutathione metabolism and nutrients digestion and absorption in late preterm infants. Overall, this study provided metagenomic and metabolomic profile of the gut microbes in full-term newborns and late preterm infants in eastern China. Further studies are needed to support and elucidate the role of probiotic feeding in late preterm infants with mandatory antimicrobial treatment.

Abstract The PI3K-Akt-mTOR (PAM) pathway is implicated in tumor progression in many tumor types, including metastatic gastric cancer (GC). The initial promise of PAM inhibitors has been unrealized in the clinic, presumably due, in part, to the up-regulation of Akt signaling that occurs when the pathway is inhibited. Here we present that DIACC3010 (formerly M2698), an inhibitor of two nodes in the PAM pathway, p70S6K and Akt 1/3, blocks the pathway in in vitro and in vivo preclinical models of GC while providing a mechanism that inhibits signaling from subsequent Akt up-regulation. Utilizing GC cell lines and xenograft models, we identified potential markers of DIACC3010-sensitivity in Her2-negative tumors, i.e., PIK3CA mutations, low basal pERK, and a group of differentially expressed genes (DEGs). The combination of DIACC3010 and trastuzumab was evaluated in Her2-positive cell lines and models. Potential biomarkers for the synergistic efficacy of the combination of DIACC3010 + trastuzumab also included DEGs as well as a lack of up-regulation of pERK. Of 27 GC patient-derived xenograft (PDX) models tested in BALB/c nu/nu mice, 59% were sensitive to DIACC3010 + trastuzumab. Of the 21 HER2-negative PDX models, DIACC3010 significantly inhibited the growth of 38%. Altogether, these results provide a path forward to validate the potential biomarkers of DIACC3010 sensitivity in GC and support clinical evaluation of DIACC3010 monotherapy and combination with trastuzumab in patients with HER2- negative and positive advanced GCs, respectively.

Abstract The large-scale simulation of dynamical systems is critical in numerous scientific and engineering disciplines. However, traditional numerical solvers are limited by the choice of step sizes when estimating integration, resulting in a trade-off between accuracy and computational efficiency. To address this challenge, we introduce a deep learning-based corrector called Neural Vector (NeurVec), which can compensate for integration errors and enable larger time step sizes in simulations. Our extensive experiments on a variety of complex dynamical system benchmarks demonstrate that NeurVec exhibits remarkable generalization capability on a continuous phase space, even when trained using limited and discrete data. NeurVec significantly accelerates traditional solvers, achieving speeds tens to hundreds of times faster while maintaining high levels of accuracy and stability. Moreover, NeurVec’s simple-yet-effective design, combined with its ease of implementation, has the potential to establish a new paradigm for fast-solving differential equations based on deep learning.

Abstract In the context of “space of flows”, city-based innovation correlation in driving economic growth is no longer limited to the traditional hierarchical structure. It is of great significance to explore Chinese cities innovation association network from the perspective of high-tech zones which gather a large number of innovation resources. Here our report is to provide new ideas for improving the innovation capability of high-tech zones and accelerating the construction of Chinese high-quality innovation system. Here we take 142 cities with high-tech zones as research samples, and explore the characteristics and influencing factors of spatial network of city-based innovation correlation in China, through modified gravity modelsocial, network analysis and QAP analysis. The results show that city-based innovation network is not closely connected, the number of redundant connection channels is low efficiency, showing a four-level spatial pattern of “Z” shaped spindle. Among them, degree centrality of cities in eastern China is higher than that in the western region, the core cities in central China play a bridging role, and western remote cities are easily affected by related cities. Moreover, there are four innovation cohesion subgroups, including the northern hinterland subgroup, the eastern coastal subgroup, the southern subgroup and the western cooperation subgroup. Furthermore, the results of the influencing factors analysis show the differences in administrative level, economic development level, openness to the outside world, and investment in technology are conducive to the innovation association between cities, while the similarities in spatial adjacency and industrial structure will promote the strong innovation association between cities.

Abstract Dentin sialophosphoprotein (DSPP) is primarily expressed by differentiated odontoblasts (dentin-forming cells), and transiently expressed by presecretory ameloblasts (enamel-forming cells). Disease-causing DSPP mutations predominantly fall into two categories: 5’ mutations affecting targeting and trafficking, and 3’ − 1 frameshift mutations converting the repetitive, hydrophilic, acidic C-terminal domain into a hydrophobic one. We characterized the dental phenotypes and investigated the pathological mechanisms of Dspp P19L and Dspp −1fs mice that replicate the two categories of human DSPP mutations. In Dspp P19L mice, dentin is less mineralized but contains dentinal tubules. Enamel mineral density is reduced. Intracellular accumulation and ER retention of DSPP is observed in odontoblasts and ameloblasts. In Dspp −1fs mice, a thin layer of reparative dentin lacking dentinal tubules is deposited. Odontoblasts show severe pathosis, including intracellular accumulation and ER retention of DSPP, strong ubiquitin and autophagy activity, ER-phagy, and sporadic apoptosis. Ultrastructurally, odontoblasts show extensive autophagic vacuoles, some of which contain fragmented ER. Enamel formation is comparable to wild type. These findings distinguish molecular mechanisms underlying the dental phenotypes of Dspp P19L and Dspp −1fs mice and support the recently revised Shields classification of dentinogenesis imperfecta caused by DSPP mutations in humans. The Dspp −1fs mice may be valuable for the study of autophagy and ER-phagy.

Abstract The increasing trend in the incidence of adverse perinatal outcomes is a public health concern globally as well as in China. However, the causes of the increasing trend are not well understood. The present tertiary-hospital-based retrospective study (2011–2019) aims to determine the secular trends and age-period-cohort effect on adverse perinatal outcomes in Hubei, China. The age-standardized incidence rates of adverse perinatal outcomes significantly decreased such as preterm births by 22% [AAPC − 3.4% (95% CI − 7.8, − 1.2)], low birth weight (LBW) by 28.5% [AAPC − 4.7% (95% CI − 6.0, − 3.3)], and fetal distress by 64.2% [AAPC − 14.0% (95% CI − 17.8, − 10.0)] during 2011–2019. Both extremes of maternal age groups (18–20 years and 42–44 years) had a higher risk ratio for adverse perinatal outcomes including preterm birth, perinatal mortality, LBW, low ponderal index (LPI), low Apgar score, and congenital defect compared to the reference age group (30–32 years). A higher risk ratio for perinatal mortality, intrauterine growth restriction (IUGR), and fetal distress and a lower risk ratio for preterm births and LBW were observed in the period 2017–2019. Both the young cohort (1997–1999) and the old cohort (1976–1969) had a higher risk ratio for preterm birth, perinatal mortality, macrosomia, and congenital defect compared to the reference cohort (1982–1984). In conclusion, some of the adverse perinatal outcomes incidence significantly decreased in the last 9 years in Hubei. However, extremes of maternal age groups and both young and old cohorts were associated with a higher risk of preterm birth, perinatal mortality, and congenital defect.

Abstract Influenza A(H3N2) virus exhibited complex seasonal patterns to evade pre-existing antibodies, resulting in changes in the antigenicity of the viron surface protein hemagglutinin (HA). To monitor the currently imported influenza viruses as well as to assess the capacity of health emergencies at the Shanghai port, we collected respiratory specimens of passengers from different countries and regions including some of Europe with influenza-like illness at the Shanghai port during 2016/2017, examined amino acid substitutions, and calculated the perfect-match vaccine efficacy using the p epitope model. Phylogenetic analysis of the HA genes revealed that influenza A(H3N2) viruses belonging to eight subclades were detected, and three amino acid substitutions in the subclade 3C.2a.4 were also added. Besides, two epidemic influenza virus strains were found in the 2016/2017 winter and 2016 summer. The results of lower predicted vaccine effectiveness in summer suggest that the imported A(H3N2) strains were not a good match for the A/Hong Kong/4801/2014 vaccine strain since the summer of 2017. Therefore, the Shanghai Port might stop the risk of the international spread of influenza for the first time, and curb the entry of A(H3N2) from overseas at the earliest stage of a probable influenza pandemic.

Abstract Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4 R110C mice that carry the p.(Arg110Cys) loss-of-function mutation. Mouse Acp4 expression was the strongest at secretory stage ameloblasts, and the protein localized primarily at Tomes’ processes. While Acp4 heterozygous (Acp4 +/R110C) mice showed no phenotypes, incisors and molars of homozygous (Acp4 R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4 R110C/R110C ameloblasts appeared normal initially but underwent pathology at mid-way of secretory stage. Ultrastructurally, sporadic enamel ribbons grew on mineralized dentin but failed to elongate, and aberrant needle-like crystals formed instead. Globs of organic matrix accumulated by the distal membranes of defective Tomes’ processes. These results demonstrated a critical role for ACP4 in appositional growth of dental enamel probably by processing and regulating enamel matrix proteins around mineralization front apparatus.

Abstract miR-30c functions as a tumor suppressor gene in the majority of tumors, including gliomas. In our study, we discovered that the expression levels of miR-30c in glioma tissues and plasma prior to surgery were lower than those in normal brain tissue following brain injury decompression and in plasma in healthy volunteers. The low expression of miR-30c was closely aligned with the WHO grade, tumor size, PFS, and OS. Additionally, the miR-30c expression level in tumor tissue was positively correlated with the levels in preoperative plasma. In cell biology experiments, miR-30c inhibited EMT and proliferation, migration, and invasion of glioma cells. Analysis of databases of miRNA target genes, real-time quantitative PCR, western blotting, and dual luciferase reporter assays demonstrated that Notch1 is the direct target gene of miR-30c. An inhibitor and shRNA-Notch1 were cotransfected into glioma cells, and it was found that shRNA-Notch1 reduced the enhancement of inhibitors of EMT and proliferation, migration, and invasion of glioma cells. Therefore, we believe that when utilized as a tumor suppressor gene, miR-30c can inhibit EMT and the proliferation, migration, and invasion of glioma cells by directly acting on Notch1 at the posttranscriptional level and that it is a potential diagnostic and prognostic marker.

Abstract Synovial fluid-derived mesenchymal stem cells (SFMSCs) play important regulatory roles in the physiological balance of the temporomandibular joint. Interleukin (IL)-1β regulates the biological behavior of SFMSCs; however, the effects of IL-1β on long noncoding RNA (lncRNA) and mRNA expression in SFMSCs in the temporomandibular joint are unclear. Here, we evaluated the lncRNA and mRNA expression profiles of IL-1β-stimulated SFMSCs. Using microarrays, we identified 264 lncRNAs (203 upregulated, 61 downregulated) and 258 mRNAs (201 upregulated, 57 downregulated) that were differentially expressed after treatment with IL-1β (fold changes ≥ 2, P

Abstract To compare the efficacy of peripherally inserted central catheters (PICCs) and totally implantable venous-access ports (TIVAPs) for chemotherapy of pediatric patients with malignant tumors. A total of 96 children with malignant tumors who received catheterization of PICCs or TIVAPs for chemotherapy from May 2020 to May 2021 in Department of Pediatric Oncology of Qilu Hospital of Shandong University were selected. Then, the pathological features of disease, the age of children, the indwelling time, the incidence of postoperative complications, and the satisfaction degree were compared between the two groups. The age of children in the TIVAP group was younger than that in the PICC group (P

Abstract Recently, plant essential oils (EOs) have attracted special attention in plant disease control and food preservation. Since ancient times, essential oils extracted from plants have exhibited many biological characteristics, especially antimicrobial properties. Recent studies have described the potentials of EOs and derivatives to inhibit the growth and reproduction of microorganisms, mainly in response of overwhelming concerns of consumers about food safety. In the context of returning to nature, with the advancement of science and technology and improved living standards, people have begun to seek solutions for food hygiene without chemical additives. Therefore, biological pesticides and plant-oriented chemicals have received special attention from scientists because they are environmentally friendly and nonhazardous, sustainable, and effective alternatives against many noxious phytopathogens. Present study is intended to appraise the fungicidal properties of ginger EOs to combat leaf blight disease of taro, which threatens global taro production. Farmers often hinge on extremely toxic synthetic fungicides to manage diseases, but the residual effects and resistance of chemicals are unavoidable. The microwave-assisted hydrodistillation method was used for ginger EOs extraction and an FTIR (ATR) spectrometer was used to evaluate their chemical composition and citral was identified as most abundant compound (89.05%) in oil. The pathogen isolated from lesions of diseased taro plants was identified as Phytophthora colocasiae and used as test fungus in the present study. Ginger EO was evaluated in-vitro for antifungal properties against mycelium growth, sporangium production, zoospore germination, leaf, and corm necrosis inhibition. Repeated experiments have shown that the concentration of ginger essential oil (1250 ppm) proved to be the lowest dose to obtain 100% inhibition of fungal growth and spore germination, sporangia formation and leaf necrosis assessment. These results are derived from this fungal species and a hypothesis that involves further research on other plant pathogens to demonstrate the overall potency of essential oils. This study references the easy, economic, and environmental management and control of plant diseases using essential oils and byproducts.

Abstract The pathogenic variant Phe508del of the CFTR-gene is the most frequent cause of cystic fibrosis (CF). Whereas male CF-patients are infertile due to bilateral agenesis of the efferent ducts, the fertility status of male heterozygous carriers is uncertain. We aimed at demonstrating the involvement of the CFTR-ion channel during sperm capacitation and to potentially select variant-free spermatozoa in heterozygous carriers of the CFTR-variant using flow cytometry (FC). Using FC and sorting, single cell polymerase chain reaction, immuno-fluorescent staining an experimental study was performed on nine fertile semen donors and three heterozygous infertile men carrying the Phe508del gene variant. Chemical inhibition of CFTR interfered with sperm capacitation. Most viable spermatozoa of heterozygous carriers of the Phe508del variant of the CFTR-gene show immune-fluorescent CFTR. Sperm capacitation in Phe508del carriers was similar to that in healthy semen donors. Distribution of the Phe508del allele in trio data of CF-affected families corresponded to the expected recessive inheritance pattern. Infertility in Phe508del heterozygous men is unlikely to be caused by the pathogenic variant although some contribution cannot be excluded. Normal sperm capacitation in carriers of pathogenic variants of the Phe508del-gene may in part explain the high prevalence of a potentially lethal recessive disorder.

Abstract Diabetes can cause microvessel impairment. However, these conjunctival pathological changes are not easily recognized, limiting their potential as independent diagnostic indicators. Therefore, we designed a deep learning model to explore the relationship between conjunctival features and diabetes, and to advance automated identification of diabetes through conjunctival images. Images were collected from patients with type 2 diabetes and healthy volunteers. A hierarchical multi-tasking network model (HMT-Net) was developed using conjunctival images, and the model was systematically evaluated and compared with other algorithms. The sensitivity, specificity, and accuracy of the HMT-Net model to identify diabetes were 78.70%, 69.08%, and 75.15%, respectively. The performance of the HMT-Net model was significantly better than that of ophthalmologists. The model allowed sensitive and rapid discrimination by assessment of conjunctival images and can be potentially useful for identifying diabetes.

Abstract Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5′ mutations affecting an N-terminal targeting sequence and 3′ mutations that shift translation into the − 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp −1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a Dspp P19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. Dspp P19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. Dspp P19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp −1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp +/+ and Dspp P19L dentin. The Dspp −1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5′ and 3′ Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.

Abstract Similar to global trends, the incidence rate of tuberculosis (TB) in China declined from 2000 to 2018. In this study, we aimed to evaluate TB trends in northern Guizhou Province and identify risk factors associated with rifampicin-resistant (RR) and concurrent extrapulmonary TB (EPTB). We analyzed data of TB patients hospitalized in Affiliated Hospital of Zunyi Medical University from 2011 to 2018, and assessed correlations between demographic characteristics of patients and RR-TB as well as concurrent EPTB. Our results showed that numbers of new, retreated, RR-TB and concurrent EPTB cases increased gradually from 2011 to 2018. Retreated patients had the highest odds of RR-TB but a lower likelihood of concurrent EPTB compared to new patients. Patients between 21 and 40 years of age had a higher likelihood of RR-TB compared to those 20 years and younger. Female patients and patients from Bijie city as well as the Miao ethnic minority had higher odds of concurrent EPTB. In summary, our data demonstrate upward trends in new, rifampicin-resistant and concurrent extrapulmonary TB cases in northern Guizhou Province of China, which should not be overlooked especially during and post the COVID-19 pandemic because TB is a greater long-term global health threat than COVID-19.

Abstract Cadmium (Cd) is highly toxic to living organisms and the contamination of Cd in paddy soil in China has received much attention. In the present study, by conducting pot experiment, the influence of S fertilizer (S0) on rice growth, iron plaque formation, Cd accumulation in rice plants and bacterial community in rice rhizosphere soil was investigated. The biomass of rice plants was significantly increased by S0 addition (19.5–73.6%). The addition of S0 increased the formation of iron plaque by 24.3–45.8%, meanwhile the amount of Cd sequestered on iron plaque increased. In soil treated with 5 mg/kg Cd, addition of 0.2 g/kg S0 decreased the diffusive gradients in thin films (DGT) extractable Cd by 60.0%. The application of S0 significantly decreased the concentration of Cd in rice grain by 12.1% (0.1 g/kg) and 36.6% (0.2 g/kg) respectively. The addition of S0 significantly increased the ratio of Acidobacteria, Bacteroidetes in rice rhizosphere soil. Meanwhile, the ratio of Planctomycetes and Chloroflexi decreased. The results indicated that promoting Fe- and S-reducing and residue decomposition bacterial in the rhizosphere by S0 may be one biological reason for reducing Cd risk in the soil-rice system.

Abstract The aim of the study is to explore the distribution patterns and internal correlations of the morphological parameters of the cornea in patients with age-related cataract. The Pentacam HR was used to measure anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), total corneal astigmatism (TCA) and keratometric corneal astigmatism (KCA). With age, the proportion of with-the-rule (WTR) ACA decreased from 65.31% to 23.63%, while the against-the-rule (ATR) ACA increased from 26.53% to 56.20%. PCA exceeded 0.50 D in 9.14% of eyes, while 76.35% of them were ATR. The magnitude of ACA was positively correlated with PCA in the whole sample, with a more significant correlation in WTR eyes (sr = 0.349, P

Abstract Fish sex identification is a basic technique of great importance for both fish genetic studies and fisheries. Due to the sexual reversal phenomenon in many fish species, a simple and rapid molecular identification method for fish genetic sex is urgently needed to suit versatile detection scenarios, such as point-of-need applications. In this study, we took Cynoglossus semilaevis as an example, established a recombinase-aided amplification (RAA)-based method for sex identification, and combined the RAA-detection with two result visualization approaches with distinct features, capillary electrophoresis (CE) and lateral flow dipstick (LFD). Specific primers and probe were designed to specifically detect the sex chromosome W of C. semilaevis in order to distinguish the genetic sex between males, pseudo-males and females. To evaluate the performance of our methods, the genetic sex for twenty-eight males, sixty-eight pseudo-males and fifty-four females were examined with the RAA-based method and classical PCR-based genotyping method, demonstrating the consistent results of sex identification between both methods. The RAA-LFD method is operationally simple, rapid (~ 30 min) and holds great potential for point-of-need applications of fish sex identification, including fishery fields. The method presented here could be effective for identifying fish gender with the ZW karyotype.

Abstract The aim is to investigate that 17β-estradiol (E2)/estrogen receptors (ERs) activation normalizes splenic CD4 + T lymphocytes proliferation and cytokine production through inhibition of endoplasmic reticulum stress (ERS) following hemorrhage. The results showed that hemorrhagic shock (hemorrhage through femoral artery, 38–42 mmHg for 90 min followed by resuscitation of 30 min and subsequent observation period of 180 min) decreased the CD4+ T lymphocytes proliferation and cytokine production after isolation and incubation with Concanavalin A (5 μg/mL) for 48 h, induced the splenic injury with evidences of missed contours of the white pulp, irregular cellular structure, and typical inflammatory cell infiltration, upregulated the expressions of ERS biomarkers 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6). Either E2, ER-α agonist propyl pyrazole triol (PPT) or ERS inhibitor 4-Phenylbutyric acid administration normalized these parameters, while ER-β agonist diarylpropionitrile administration had no effect. In contrast, administrations of either ERs antagonist ICI 182,780 or G15 abolished the salutary effects of E2. Likewise, ERS inducer tunicamycin induced an adverse effect similarly to that of hemorrhagic shock in sham rats, and aggravated shock-induced effects, also abolished the beneficial effects of E2 and PPT, respectively. Together, the data suggest that E2 produces salutary effects on CD4+ T lymphocytes function, and these effects are mediated by ER-α and GPR30, but not ER-β, and associated with the attenuation of hemorrhagic shock-induced ERS.

Abstract To quantitatively analyze changes in the inner components of the human crystalline lens during accommodation in adults. Eyes of 23 subjects were sequentially examined using CASIA2 Optical Coherence Tomography under 0D, − 3D and − 6D accommodation states. The anterior chamber depth (ACD), anterior and posterior crystalline lens radius of the curvature (ALRC and PLRC) were obtained using built-in software. The lens thickness (LT), lenticular nucleus thickness (NT), anterior cortex thickness (ACT), posterior cortex thickness (PCT), anterior and posterior lenticular nucleus radius of the curvature (ANRC and PNRC), anterior and posterior lenticular nucleus vertex (ANV and PNV) were quantified manually with the Image-pro plus software. During accommodation, the ACD became significantly shallower and LT significantly increased. For changes in the lens, the ALRC decreased by an average magnitude (related to accommodative stimuli) 0.44 mm/D, and PLRC decreased 0.09 mm/D. There was no difference for the ACT and PCT in different accommodation states. For lenticular nucleus response, NT increased on average by 30 μm/D. Both the ANRC and PNRC decreased on average by 212 μm/D and 115 μm/D respectively. The ANV moved forward on average by 0.07 mm under − 3D accommodative stimuli and 0.16 mm for − 6D. However, there was no statistically significant difference between different accommodation states in the PNV movement. Under accommodation stimulation, lens thickness changed mainly due to the lenticular nucleus, but not the cortex. For the lenticular nucleus, both the ANRC and PNRC decreased and ANRC changed the most. The anterior surface of the nucleus moved forward while the posterior surface of the nucleus moved backward but only slightly.

Abstract Aspergillus species are emerging causative agents of non-dermatophyte mold onychomycosis. In this study, 48 Aspergillus isolates were obtained from patients with onychomycosis in Mashhad, Iran, during 2015–2018. The aim is to identify the Aspergillus isolates to the species level by using partial calmodulin and beta-tubulin gene sequencing and MALDI-TOF MS, and to evaluate their in vitro susceptibility to ten antifungal drugs: terbinafine, itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, caspofungin, micafungin, anidulafungin and amphotericin B according to CLSI M38-A3. Our results indicate that A.flavus (n = 38, 79%) is the most common Aspergillus species causing onychomycosis in Mashhad, Iran. Other detected species were A. terreus (n = 3), A. tubingensis (n = 2), A. niger (n = 1), A. welwitschiae (n = 1), A. minisclerotigenes (n = 1), A. citrinoterreus (n = 1) and A. ochraceus (n = 1). Aspergillus flavus, A. terreus and A. niger isolates were correctly identified at the species level by MALDI-TOF MS, while all cryptic species were misidentified. In conclusion, A. flavus is the predominant Aspergillus species causing onychomycosis due to Aspergillus spp. in Mashhad, Iran. MALDI-TOF MS holds promise as a fast and accurate identification tool, particularly for common Aspergillus species. It is important that the current database of reference spectra, representing different Aspergillus species is expanded to increase the precision of the species-level identification. Terbinafine, posaconazole and echinocandins were in vitro most active against the studies Aspergillus isolates and terbinafine could be the first choice for treatment of onychomycosis due to Aspergillus.

Abstract Mutations of Odontogenesis-Associated Phosphoprotein (ODAPH, OMIM *614829) cause autosomal recessive amelogenesis imperfecta, however, the function of ODAPH during amelogenesis is unknown. Here we characterized normal Odaph expression by in situ hybridization, generated Odaph truncation mice using CRISPR/Cas9 to replace the TGC codon encoding Cys41 into a TGA translation termination codon, and characterized and compared molar and incisor tooth formation in Odaph +/+, Odaph +/C41*, and Odaph C41*/C41* mice. We also searched genomes to determine when Odaph first appeared phylogenetically. We determined that tooth development in Odaph +/+ and Odaph +/C41* mice was indistinguishable in all respects, so the condition in mice is inherited in a recessive pattern, as it is in humans. Odaph is specifically expressed by ameloblasts starting with the onset of post-secretory transition and continues until mid-maturation. Based upon histological and ultrastructural analyses, we determined that the secretory stage of amelogenesis is not affected in Odaph C41*/C41* mice. The enamel layer achieves a normal shape and contour, normal thickness, and normal rod decussation. The fundamental problem in Odaph C41*/C41* mice starts during post-secretory transition, which fails to generate maturation stage ameloblasts. At the onset of what should be enamel maturation, a cyst forms that separates flattened ameloblasts from the enamel surface. The maturation stage fails completely.

Abstract Senescence is a degenerative process triggered by intricate and coordinated regulatory networks, and the mechanisms of age-dependent senescence and stress-induced premature senescence still remain largely elusive. Thus we selected leaf samples of developmental senescence (DS) and premature senescence (PS) to reveal the regulatory divergence. Senescent leaves were confirmed by yellowing symptom and physiological measurement. A total of 1171 and 309 genes (DEGs) were significantly expressed respectively in the whole process of DS and PS. Up-regulated DEGs in PS were mostly related to ion transport, while the down-regulated DEGs were mainly associated with oxidoreductase activity and sesquiterpenoid and triterpenoid biosynthesis. In DS, photosynthesis, precursor metabolites and energy, protein processing in endoplasmic reticulum, flavonoid biosynthesis were notable. Moreover, we found the vital pathways shared by DS and PS, of which the DEGs were analyzed further via protein–protein interaction (PPI) network analysis to explore the alteration responding to two types of senescence. In addition, plant hormone transduction pathway was mapped by related DEGs, suggesting that ABA and ethylene signaling played pivotal roles in formulating the distinction of DS and PS. Finally, we conducted a model containing oxidative stress and ABA signaling as two hub points, which highlighted the major difference and predicted the possible mechanism under DS and PS. This work gained new insight into molecular divergence of developmental senescence and premature senescence and would provide reference on potential mechanism initiating and motivating senescence for further study.

Abstract Scytalidium auriculariicola is the causative pathogen of slippery scar disease in the cultivated cloud ear fungus, Auricularia polytricha. In the present study, the mitogenome of S. auriculariicola was sequenced and assembled by next-generation sequencing technology. The circular mitogenome is 96,857 bp long and contains 56 protein-coding genes, 2 ribosomal RNA genes, and 30 transfer RNA genes (tRNAs). The high frequency of A and T used in codons contributed to the high AT content (73.70%) of the S. auriculariicola mitogenome. Comparative analysis indicated that the base composition and the number of introns and protein-coding genes in the S. auriculariicola mitogenome varied from that of other Leotiomycetes mitogenomes, including a uniquely positive AT skew. Five distinct groups were found in the gene arrangements of Leotiomycetes. Phylogenetic analyses based on combined gene datasets (15 protein-coding genes) yielded well-supported (BPP = 1) topologies. A single-gene phylogenetic tree indicated that the nad4 gene may be useful as a molecular marker to analyze the phylogenetic relationships of Leotiomycetes species. This study is the first report on the mitochondrial genome of the genus Scytalidium, and it will contribute to our understanding of the population genetics and evolution of S. auriculariicola and related species.

Abstract The impact of plants growing on buildings remains controversial, especially for vulnerable historic walls and ruins requiring on-going conservation. English ivy (Hedera helix L.) can cause considerable damage where it is able to grow into deteriorating masonry, yet in some circumstances it may be protective. Here we focus on the potential of ivy to buffer damaging thermal cycles and frost events that can contribute to the deterioration of masonry materials. On limestone masonry test walls in central Southern England (Wytham near Oxford, UK), ivy foliage had a significant influence on stone-surface freezing regimes. Over two successive winters (2012/13 and 2013/14) the frequency of freezing events under ivy was reduced on average by 26%, their duration by 34% and their severity by 32%. A subsequent laboratory simulation showed that stone mass loss, surface softening, and textural development were all significantly reduced under an ‘ivy covered’ thermal regime. Cautious extrapolation indicates that ivy can reduce frost-driven granular-scale decay of limestone by the order of 30 g m−2 yr−1, depending on the local freezing regime. Whilst the capacity of ivy to cause damage should not be underplayed, vertical greenery can aid heritage conservation efforts by mitigating specific environmental threats.

Abstract Drought is the No. 1 factor that limits agricultural production in the world, thus, making crops more drought tolerant is a major goal in agriculture. Many genes with functions in abiotic stress tolerance were identified, and overexpression of these genes confers increased drought tolerance in transgenic plants. The isopentenyltransferase gene (IPT) that encodes a rate limiting enzyme in cytokinin biosynthesis is one of them. Interestingly, when IPT-transgenic cotton was field-tested at two different sites, Texas and Arizona, different results were obtained. To explain this phenomenon, reduced irrigation experiments with different timing in applying water deficit stress were conducted. It was found that the timing of water deficit stress is critical for IPT-transgenic cotton to display its yield advantage over control plants (i.e. wild-type and segregated non-transgenic plants). If water deficit stress occurs before flowering (vegetative phase), IPT-transgenic cotton would outperform control plants; however, if water deficit stress occurs at or after flowering (reproductive phase), there would not be a yield difference between IPT-transgenic and control cotton plants. This result suggests that an early induction of IPT expression (before first flowering) is needed in order to realize the benefits of IPT-expression in transgenic plants that face water-deficit stress later in development.

Abstract Spiral waves are shown to undergo directional drifts in the presence of ac and polarized electric fields when their frequencies are twice of the spiral frequencies. Here, we propose a quantitative description for the spiral wave drift induced by weak electric fields, and provide the explicit equations for the spiral wave drift speed and direction. Numerical simulations are performed to demonstrate the quantitative agreement with analytical results in both weakly and highly excitable media.

Abstract Streptomyces lydicus A02 is used by industry because it has a higher natamycin-producing capacity than the reference strain S. natalensis ATCC 27448. We sequenced the complete genome of A02 using next-generation sequencing platforms, and to achieve better sequence coverage and genome assembly, we utilized single-molecule real-time (SMRT) sequencing. The assembled genome comprises a 9,307,519-bp linear chromosome with a GC content of 70.67%, and contained 8,888 predicted genes. Comparative genomics and natamycin biosynthetic gene cluster (BGC) analysis showed that BGC are highly conserved among evolutionarily diverse strains, and they also shared closer genome evolution compared with other Streptomyces species. Forty gene clusters were predicted to involve in the secondary metabolism of A02, and it was richly displayed in two-component signal transduction systems (TCS) in the genome, indicating a complex regulatory systems and high diversity of metabolites. Disruption of the phoP gene of the phoR-phoP TCS and nsdA gene confirmed phosphate sensitivity and global negative regulation of natamycin production. The genome sequence and analyses presented in this study provide an important molecular basis for research on natamycin production in Streptomyces, which could facilitate rational genome modification to improve the industrial use of A02.

Abstract Anion exchanger 2 (AE2, encoded by SLC4A2) is a sodium-independent chloride/bicarbonate transporter and implicated in the regulation of intracellular pH and membrane potential. Previous studies have linked AE2 to the tumorigenesis of various cancers. Here, AE2 was identified as an up-regulated protein in ovarian cancer tissues compared to adjacent non-tumor lesions based on quantitative proteomics analysis. AE2 mRNA was also overexpressed in human ovarian cancer samples, and that AE2 overexpression correlated with the shortened survival time of ovarian cancer patients. Short-hairpin RNA-mediated knockdown of AE2 in A2780 and SK-OV-R3 cells inhibited cell growth and induced cell cycle G1 phase arrest. In nude mice, its stable knockdown inhibited the tumorigenicity of A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset identified that the cell cycle process and mTOR pathway were correlatively with the AE2 expression. Expression of key regulators of G1/S transition (Cyclin D1 and CDK4), and phosphorylation levels of p70S6K were notably reduced in AE2 knockdown cells. Moreover, experiments with mTOR inhibitor suggested that AE2 may promote cell cycle progression through mTOR/p70S6K1 pathway. Together, our results suggest up-regulated AE2 promotes ovarian cancer tumorigenesis by activating mTOR/p70S6K1 pathway and implicate the potential application of AE2 in cancer therapy.