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A new Diaphanopterodea (Insecta, Palaeoptera, Megasecopteromorpha), Sinoelmoa yangquanensis gen. et sp. nov., is described based on a single specimen discovered from the Shuiquan Gully locality (Shanxi Formation; Permian, Cisuralian, Asselian; China). A broad comparative analysis of the wing venation of the known members of the diaphanopterodean families Parelmoidae and Elmoidae allowed assigning the new taxon to the former family. This new occurrence represents the first record of a Permian Diaphanopterodea from China, and both the earliest and most oriental record for the Parelmoidae. It sheds new light on the distribution and diversity of these extinct taxa.

With the advance of Automated Guided Vehicles (AGVs) technology, the scheduling of multiple AGVs in a matrix manufacturing workshop has attracted considerable attention. However, little attention has been devoted to dynamic unloading time for multiple AGVs scheduling. This paper investigates a new multi-AGVs scheduling problem with dynamic unloading time (MAGVS $_{\mathrm {DUT}}$ ) in a matrix manufacturing workshop with the objective of minimizing the transportation cost, including travel cost, penalty cost, and vehicle cost. To solve MAGVSDUT, a mixed-integer linear programming model and a discrete Jaya (DJaya) algorithm are proposed. At first, a heuristic based on ant colony algorithm is designed to generate high-quality initial solution. And then, two DJaya operators are designed, one of which is a near optimal operator updating solutions towards better solutions found, while the other is the away worst operator updating solutions towards worst solutions. In addition, a sequence insertion operator is designed to help the population find better solutions within the global space. Finally, a battery of comparative experiments is conducted in conjunction with the actual situation of an electronic equipment manufacturing company. The computational results show that the proposed DJaya algorithm is superior to the existing algorithms in tackling the considered problem.

Abstract DNA methylation at the fifth position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification for regulating gene expression, but little is known about how it regulates gene expression in insects. Here, we pursue the detailed molecular mechanism by which DNMT1-mediated 5mC maintenance regulates female reproduction in the German cockroach, Blattella germanica. Our results show that Dnmt1 knockdown decreases the level of 5mC in the ovary, upregulating numerous genes during choriogenesis, especially the transcription factor ftz-f1. The hypomethylation at the ftz-f1 promoter region increases and prolongs ftz-f1 expression in ovarian follicle cells during choriogenesis, which consequently causes aberrantly high levels of 20-hydroxyecdysone and excessively upregulates the extracellular matrix remodeling gene Mmp1. These changes further impair choriogenesis and disrupt fertilization by causing anoikis of the follicle cells, a shortage of chorion proteins, and malformation of the sponge-like bodies. This study significantly advances our understanding of how DNA 5mC modification regulates female reproduction in insects.

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall-associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.

IntroductionPower industry is one of the largest sources of CO2 emissions in China. The Yellow River Basin plays a supportive role in guaranteeing the effective supply of electricity nationwide, with numerous power generation bases. Understanding the drivers and peak of CO2 emissions of power industry in the Yellow River Basin is vital for China to fulfill its commitment to reach carbon emissions peak by 2030.MethodsThe Logarithmic Mean Divisia Index (LMDI) model was employed to explore the drivers to the change of CO2 emissions in power industries of three study areas, including Inner Mongolia Autonomous Regions, Shanxi Province, and Shandong Province in the Yellow River Basin. And Back Propagation (BP) neural network was combined with scenario analysis to empirically predict the trend of the amount of CO2 emitted by power industry (CEPI) from provincial perspective.ResultsCEPI in Inner Mongolia under the scenarios of a low degree of CO2 emissions promotion with a medium degree of CO2 emissions inhibition (LM) and a low degree of CO2 emissions promotion with a high degree of CO2 emissions inhibition (LH) scenario can reach a peak as early as 2030, with the peak value of 628.32 and 638.12 million tonnes, respectively. Moreover, in Shanxi, only CEPI under a low degree of CO2 emissions promotion scenarios (LL, LM, LH) can achieve the peak in 2025 ahead of schedule, with amounts of 319.32, 308.07, and 292.45 million tonnes. Regarding Shandong, CEPI under scenarios of a low degree of CO2 emissions promotion with a high degree of CO2 emissions inhibition (LH) and a medium degree of CO2 emissions promotion with a high degree of CO2 emissions inhibition (MH) could achieve the earliest peak time in 2025, with a peak of 434.6 and 439.36 million tonnes, respectively.DiscussionThe earliest peak time of CEPI in Shandong Province and Shanxi Province is 2025, but the peak of CEPI in Shanxi is smaller than that of Shandong. The peak time of CEPI in Inner Mongolia is relatively late, in 2030, and the peak is larger than that of the other two provinces. The per capita GDP is the most positive driving factor that contributes to the CEPI. Shandong has a strong economy, and its per capita GDP is much higher than Shanxi’s. Therefore, even under the same peak time, the CEPI in Shandong is much higher than that of Shanxi. Inner Mongolia is extensive and sparsely populated, which makes its per capita GDP rank among the top in China. In addition, Inner Mongolia’s coal-based power generation structure and high power generation also contribute to its late CO2 peak time and large CO2 peak.

Abstract Currently, studies of ancient faunal community networks have been based mostly on uniformitarian and functional morphological evidence. As an important source of data, taphonomic evidence offers the opportunity to provide a broader scope for understanding palaeoecology. However, palaeoecological research methods based on taphonomic evidence are relatively rare, especially for body fossils in lacustrine sediments. Such fossil communities are not only affected by complex transportation and selective destruction in the sedimentation process, they also are strongly affected by time averaging. Historically, it has been believed that it is difficult to study lacustrine entombed fauna by a small-scale quadrat survey. Herein, we developed a software, the TaphonomeAnalyst, to study the associational network of lacustrine entombed fauna, or taphocoenosis. TaphonomeAnalyst allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. The dataset for these investigations resulted from fieldwork of the latest Middle Jurassic Jiulongshan Formation near Daohugou Village, in Ningcheng County of Inner Mongolia, China, spotlighting the core assemblage of the Yanliao Fauna. Our data included 27,000 fossil specimens of animals from this deposit, the Yanliao Fauna, whose analyses reveal sedimentary environments, taphonomic conditions, and co-occurrence networks of this highly studied assemblage, providing empirically robust and statistically significant evidence for multiple Yanliao habitats.

The identification and quantification of aeolian sand contributions are essential for understanding the formation of dune fields and mechanisms of modern surface processes. In the present study, we take aeolian sand in the Otindag dune field (hereafter, often referred to as, simply, Otindag) as the research object. The dune field’s immediate source is quantitatively identified based on heavy minerals and the Conservativeness Index (CI), Consensus Ranking (CR), and the Consistent Tracer Selection (CTS) method. The primary source area of the aeolian sand was found to be from the northwestern, upwind area of the Otindag (59 ± 14%), followed by the Yinshan Mountain (17 ± 10%) and the lake basin (23 ± 12%). The proposed sediment transport model elucidates that sediments from the upwind of the Otindag are directly transported from the northwest to the Otindag, where they are deposited. Materials from the southern Yinshan Mountains are carried by rivers to the southern edge of the Otindag, where they are subsequently transported by wind and ultimately deposited. The lake deposits within the Otindag also contribute to the aeolian sand supply under the influence of wind. This study demonstrates that the fingerprinting techniques of CI, CR, and CTS serve as successful strategies for conducting quantitative provenance research in dune fields.

Investigating the intricate pathways through which FH06 fermentation broth exerts lipid-lowering and weight-loss effects is pivotal for advancing our comprehension of metabolic regulation and therapeutic interventions. Ultrahigh-performance liquid chromatography quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-QE-MS) detection and the ChEMBL database were used to determine the effective compounds in the FH06 fermentation broth and predict their targets. The TTD database and DisGeNET database were used to query obesity-related targets. The STRING database was used to construct protein interaction information. The Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to perform biological function annotation (GO) and KEGG pathway enrichment analyses of the targets. Results: A total of 85 effective compounds were screened from the fermentation broth of FH06; these compounds may act on TP53, PPARG, TNF, and other targets through 10 signaling pathways, such as the chemical carcinogenesis-receptor activation and lipid and atherosclerosis pathways, and exert pharmacological effects, such as hypoglycemic effects and weight loss. They also have anti-inflammatory, antioxidant, antitumor, and immunoregulatory effects. These findings reveal the active ingredients of FH06 fermentation broth and its multi-target and multi-channel characteristics in lipid lowering and weight loss. This study has positive implications for the clinical treatment of obesity using FH06, providing a theoretical and scientific basis for further developing of FH06-assisted lipid-lowering products.

In order to explore the effects of different amounts of mogroside (0%, 0.1%, 0.3%, 0.5%) on the quality and the storage stability of stewed pork belly. By measuring the sensory, texture, color of the stewed pork belly, as well as the pH value, TBARS value, total number of bacterial colonies and other indicators during storage, the analysis showed: When 0.3% mogroside was added, the stewed pork belly had the best taste, bright color, aroma and sweetness of Siraitia grosvenorii, and obvious effect of inhibiting fat oxidation (P

Abstract Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis (PTB), which is a granulomatous enteritis in ruminants that threatens the dairy industry’s healthy development and public health safety worldwide. Because the commercial inactivated vaccines are not completely protective and interfere with bovine tuberculosis diagnostics, we tested four fusion proteins, namely 66NC, 66CN, 90NC, and 90CN, which were constructed with MAP3527, Ag85B, and Hsp70 of MAP in different tandem combinations. Notably, 66NC, which encodes a 66 kDa fusion protein that combines in linear order MAP3527N40–232, Ag85B41–330, and MAP3527C231–361, induced a powerful and specific IFN-γ response. Immunization of C57BL/6 mice with the 66NC fusion protein formulated in Montanide ISA 61 VG adjuvant generated robust Th1, Th2, and Th17 type immune responses and strong antibody responses. The 66NC vaccine protected C57BL/6 mice against virulent MAP K-10 infection. This resulted in a reduction of bacterial load and improvement of pathological damage in the liver and intestine, in addition to a reduction of body weight loss; significantly better protection than the reported 74 F vaccine was also induced. Furthermore, vaccine efficacy correlated with the levels of IFN-γ-, TNF-α-, and IL-17A-secreting antigen-specific CD4+ and CD8+ T lymphocytes as well as with serum IFN-γ and TNF-α levels after vaccination. These results demonstrate that recombinant protein 66NC is an efficient candidate for further development into a protective vaccine in terms of inducing specific protection against MAP.

Abstract Background Identifying thyroid nodules’ boundaries is crucial for making an accurate clinical assessment. However, manual segmentation is time-consuming. This paper utilized U-Net and its improved methods to automatically segment thyroid nodules and glands. Methods The 5822 ultrasound images used in the experiment came from two centers, 4658 images were used as the training dataset, and 1164 images were used as the independent mixed test dataset finally. Based on U-Net, deformable-pyramid split-attention residual U-Net (DSRU-Net) by introducing ResNeSt block, atrous spatial pyramid pooling, and deformable convolution v3 was proposed. This method combined context information and extracts features of interest better, and had advantages in segmenting nodules and glands of different shapes and sizes. Results DSRU-Net obtained 85.8% mean Intersection over Union, 92.5% mean dice coefficient and 94.1% nodule dice coefficient, which were increased by 1.8%, 1.3% and 1.9% compared with U-Net. Conclusions Our method is more capable of identifying and segmenting glands and nodules than the original method, as shown by the results of correlational studies.

Mycobacterium tuberculosis (Mtb) is an intracellular bacterium that causes a highly contagious and potentially lethal tuberculosis (TB) in humans. It can maintain a dormant TB infection within the host. DosR (dormancy survival regulator) (Rv3133c) has been recognized as one of the key transcriptional proteins regulating bacterial dormancy and participating in various metabolic processes. In this study, we extensively investigate the still not well-comprehended role and mechanism of DosR in Mycobacterium bovis (M. bovis) Bacillus Calmette-Guérin (BCG) through a combined omics analysis. Our study finds that deleting DosR significantly affects the transcriptional levels of 104 genes and 179 proteins. Targeted metabolomics data for amino acids indicate that DosR knockout significantly upregulates L-Aspartic acid and serine synthesis, while downregulating seven other amino acids, including L-histidine and lysine. This suggests that DosR regulates amino acid synthesis and metabolism. Taken together, these findings provide molecular and metabolic bases for DosR effects, suggesting that DosR may be a novel regulatory target.

In this paper, we present a new route-based discrete time variational inequality (VI) ideal dynamic user optimal route choice (DUO) model on a transportation network with fixed signal timing at signalized intersections and a relaxation with gradient projection algorithm to solve the model. The new trait of our study is the queue length in red time and the throughput in green time for each cycle at each intersection can be found when traffic is in DUO status. This is different from other studies, in which either only average queue length or average delay in a period composing of multiple cycles can be found or traffic is not in DUO status. Furthermore, the optimal signal timings can be found by the algorithm. Under optimal signal timing, the total queuing delay of the network reaches minimum when traffic is in DUO status.

Abstract Background Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. Results Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T 1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. Conclusion The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment. Graphical Abstract

The orchid mantis Hymenopus coronatus (Insecta: Mantodea) is famous for its unique appearance, which resembles a flower blossom with petal-like legs and a whitish pink colour. Based on this appearance, H. coronatus has been hypothesized to be an aggressive mimic that attracts pollinators. Research on the orchid mantis has been sparse due to the difficulty of collection and maintenance. The first record of orchid mantis from Xishuangbanna, China, was originally named H. coronatoides but later considered synonymous with H. coronatus based on a morphological study. In this study, the complete mitochondrial genome of the orchid mantis from Xishuangbanna, China, was determined to be a circular molecule of 15,589 bp containing 37 typical mitochondrial genes in the same gene arrangement as those of other praying mantises. The relatively low degree of genetic difference between orchid mantises from China and Malaysia suggests that they belong to the same species. The phylogenetic relationships inferred from 13 protein-coding genes (PCGs) show that H. coronatus is a sister to Parymenopus davisoni, another rare species from Malaysia, and supports monophyletic Hymenopodinae, whereas Acromantinae is polyphyletic. This study provides useful data for studies on the population genetics, phylogeny and mimicry mechanism of the orchid mantis.

Changes in educational systems and English teaching strategies have increased the need for automatic methods for English Teaching Quality Evaluation (ETQE). A practical model for ETQE applies in different fields, determines the most relevant factors in teaching quality (TQ), and has optimal performance in different conditions. This paper presents a new method based on Artificial Intelligence (AI) and meta-heuristic algorithms to solve the ETQE problem. The proposed method performs the prediction process in two phases: “determination of related indicators” and “quality prediction”. During the first phase, after introducing a set of 24 candidate indicators, an optimal subset of them having maximum correlation with ETQE and minimum redundancy are selected using Artificial Bee Colony (ABC) algorithm. In the second phase of the proposed method, a Classification and Regression Tree (CART) model optimized by ABC are applied to predict ETQ based on the indicators determined in the first phase. In this learning model, split points of decision nodes are determined by ABC in a way that the prediction accuracy would be maximized. The performance of the proposed method has been evaluated in two different teaching environments. The performance of the proposed method has been evaluated in two different teaching environments. The studied teaching environments are face-to-face (FF) and online classes that were held for middle school and university students, respectively. Based on the obtained results, the proposed method can predict the ETQ with an accuracy of more than 98.99% in both tested scenarios, which results in an increase of at least 1.11% compared to the previous methods. The efficiency of the proposed model in both studied scenarios prove the generality of this method to be used in real-world applications.

As the second leading cause of cancer worldwide, colorectal cancer (CRC) is associated with a poor prognosis. Although recent studies have explored prognostic markers in patients with CRC, whether tissue microbes carry prognostic information remains unknown. Here, by assessing the colorectal tissue microbes of 533 CRC patients, we found that Proteobacteria (43.5%), Firmicutes (25.3%), and Actinobacteria (23.0%) dominated the colorectal tissue microbiota, which was different from the gut microbiota. Moreover, two clear clusters were obtained by clustering based on the tissue microbes across all samples. By comparison, the relative abundances of Proteobacteria and Bacteroidetes in cluster 1 were significantly higher than those in cluster 2; while compared with cluster 1, Firmicutes and Actinobacteria were more abundant in cluster 2. In addition, the Firmicutes/Bacteroidetes ratios in cluster 1 were significantly lower than those in cluster 2. Further, compared with cluster 2, patients in cluster 1 had relatively poor survival (Log-rank test, p = 0.0067). By correlating tissue microbes with patient survival, we found that the relative abundance of dominant phyla, including Proteobacteria, Firmicutes, and Bacteroidetes, was significantly associated with survival in CRC patients. Besides, the co-occurrence network of tissue microbes at the phylum level of cluster 2 was more complicated than that of cluster 1. Lastly, we detected some pathogenic bacteria enriched in cluster 1 that promote the development of CRC, thus leading to poor survival. In contrast, cluster 2 showed significant increases in the abundance of some probiotics and genera that resist cancer development. Altogether, this study provides the first evidence that the tissue microbiome of CRC patients carries prognostic information and can help design approaches for clinically evaluating the survival of CRC patients.

In this paper, the purification process and biological activity of proanthocyanidins isolated from Tetrastigma hemsleyanum were explored to prepare economical and efficient proanthocyanidins. The static adsorption and desorption capacity of proanthocyanidins on five kinds of resins were compared. The dynamic adsorption and desorption conditions of resins were optimized. The effects of ethanol elution on the purity and biological activity of proanthocyanidins were evaluated. The results showed that AB-8 resin was chosen as the better sorbent for the purification of proanthocyanidins from Tetrastigma hemsleyanum. The optimal conditions for purifying proanthocyanidins were as follows: Sample concentration 6.00 mg/mL, loading rate 2 BV/h, loading amount 11 BV, eluent flow rate 1.5 BV/h, and eluent volume 2 BV. 70% ethnol had the best effect for the purification of proanthocyanidins, and the purification of proanthocyanidins were 97.31%±0.96%, 2.2 times the purification of crude extract. The DPPH scavenging activity, ABTS+ scavenging activity and α-glucosidase inhibitory activity were also increased dramatically and there was a significant positive correlation between these activities and content of proanthocyanidins（P

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma which that highly aggressive and heterogeneous. Glycolysis has been implicated in the regulation of tumor microenvironment (TME) and development. In this study, we aimed to establish a glycolysis-related prognostic model for the risk stratification, prognosis prediction, and immune landscape evaluation in patients with DLBCL.Methods: Three independent datasets GSE181063, GSE10846, and GSE53786 containing gene expression profiles and clinical data were downloaded from the Gene Expression Omnibus (GEO) database. The glycolysis-related prognostic model was developed with Cox and Least Absolute Shrinkage and Selector Operation (LASSO) regression and validated. A nomogram integrating clinical factors and glycolytic risk scores was constructed. The composition of the TME was analyzed with the ESTIMATE algorithm and single-sample gene set enrichment analysis (ssGSEA).Results: A glycolytic risk model containing eight genes was developed. The area under the receiver operating characteristic (ROC) curve (AUC) for the 1-, 3-, and 5-year was 0.718, 0.695, and 0.688, respectively. Patients in the high-risk group had significantly lower immune scores, elevated tumor purity, and poorer survival compared with those in the low-risk group. The nomogram constructed based on glycolytic risk score, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), use of rituximab, and cell of origin (COO) displayed better prediction performance compared with the International Prognostic Index (IPI) in DLBCL. The glycolytic risk score was negatively correlated with the infiltration level of activated CD8 T cells, activated dendritic cells, natural killer cells, and macrophages and immune checkpoint molecules including PD-L2, CTLA4, TIM-3, TIGIT, and B7-H3.Conclusion: These results suggested that the glycolytic risk model could accurately and stably predict the prognosis of patients with DLBCL and might unearth the possible explanation for the glycolysis-related poor prognosis.

Since the 21st century, art therapy has made great progress and development in China’s education. To find out the relationship between art therapy and special children, hundreds of related literatures were analyzed using co-word analysis software, which shows that art therapy is increasingly important in special children and their education. Expressive art therapy has a good development prospect in college students’ mental health education and group counseling. The connotation of group painting therapy is constantly enriched. The theme research of mandala painting therapy is closely related, and painting art therapy focuses on the psychological counseling research of different groups, but the two are still in the marginal position in the whole research, and have not been paid attention to. Therefore, in the future research, firstly, we should continue to strengthen the research of art therapy and expressive art therapy in special education and individual mental health education; second, further broaden the depth and breadth of group painting therapy; third, strengthen the study of mandala painting therapy and painting art therapy.

It is of great practical significance to accurately distinguish the different water supply sources of rivers and lakes under climate change for regional water resources utilization. This study examines the impact of climate change on the hydrological processes of the Ranwu Lake basin in the southeastern Tibet Plateau. The authors used China Meteorological Forcing Dataset (CMFD) historical data, CanESM5′s future climate predictor, and the SPHY model to analyze trends in temperature, precipitation, and water supply sources in the basin. The study found that warming in the basin was higher than that in the Tibet Plateau, with high-altitude areas and winter showing more significant warming. From 1998 to 2018, precipitation in the basin showed a trend of fluctuation and decline. The study also found that glacial meltwater accounted for the majority of total runoff in the basin (54.13%), while snow meltwater, rainfall, and baseflow accounted for about 22.98%, 11.84%, and 11.06%, respectively, on average in recent years. The total runoff in the Ranwu Lake Basin will continue to decrease due to the accelerating retreat of glaciers, with the hydrological process transforming from being dominated by glacier processes to rain–snow processes. The study also predicts that three-quarters of glaciers in the basin will vanish within the next forty years, and by 2100, only around 20% of glaciers will remain.

BackgroundIn adolescents, multiple unhealthy behaviors frequently occur together and are likely to be associated with suicidal behaviors (SBs), increasing the risk of suicide. This study aimed to clarify the potential patterns of unhealthy behaviors in Chinese adolescents and to examine the associations between the different patterns of unhealthy behaviors and SBs.MethodsA total of 22,628 middle school students were enrolled in this study. Self-reported unhealthy behaviors and SBs were investigated using questionnaires. Latent class analysis (LCA) was performed based on five unhealthy behaviors [smoking, alcohol use (AU), diet pill use (DPU), screen time (ST), and problematic mobile phone use (PMPU)]. Multivariate logistic regressions were used to examine associations between the different patterns of unhealthy behaviors and SBs.ResultsFour subgroups of unhealthy behaviors were identified by LCA, including high-risk class (smoking/AU/DPU/PMPU/ST), moderate-risk class 1 (DPU/PMPU), moderate-risk class 2 (smoking/AU/ST), and low-risk class. Compared with the low-risk class, moderate-risk class 1, moderate-risk class 2, and high-risk class had higher risks of suicidal ideation, suicide plan, and suicide attempt.ConclusionsThese findings suggested that patterns of unhealthy behaviors were related to SBs in Chinese adolescents. Accordingly, considerations of different classes of unhealthy behaviors may be essential for developing effective preventive programs.

BackgroundEsophageal squamous cell carcinoma (ESCC) is characterized clinically by frequent recurrence, leading to a poor prognosis after radical surgery. The aim of this study was to identify a prognostic nomogram to predict the post-progression survival (PPS) of ESCC patients based on the features of primary tumor and recurrence.MethodsA total of 234 ESCC patients who underwent recurrence after radical surgery were enrolled in this study. The independent prognostic factors screened by the univariate and multivariate Cox regression analysis were subsequently used to construct a nomogram. The predictive performance of the nomogram was evaluated with the concordance index (C-index), decision curve, and the area under the receiver operating characteristic curve (AUC) and validated in two validation cohorts. The Kaplan-Meier curves of different recurrence patterns were analyzed.ResultsThe prognostic nomogram of PPS was established by integrating independent prognostic factors, including age, body mass index, number of lymph node dissection, recurrence pattern, and recurrence treatment. The nomogram demonstrated good performance, with C-index values of 0.756, 0.817, and 0.730 for the training and two validation cohorts. The 1-year AUC values were 0.773, 0.798, and 0.735 and 3-year AUC values were 0.832, 0.871, and 0.791, respectively. Furthermore, we found that patients with bone metastasis displayed the worst PPS compared to other isolated recurrence patterns.ConclusionWe constructed a nomogram to reliably predict PPS, which would be valuable to provide individual managements for ESCC patients after radical surgery.

Exploring the impacts of anthropogenic factors on vegetation cover and future spatiotemporal trends in vegetation cover change are of great practical significance for sustainable management of the ecological environment. This study used the residual, trend analysis, Hurst index, and geographic detector methods to explore the spatiotemporal trends in the effects of anthropogenic factors on vegetation cover in Guanzhong, China from 2001 to 2018. The contributions of different kinds of anthropogenic factors to vegetation cover were quantitatively decomposed to identify those with the most effect. The main conclusions of the study included: 1) Although there was a positive trend in the effects of anthropogenic factors on vegetation cover from 2001 to 2018, this trend was projected to become negative in the future. This transition was evident in 45.53% of the total study area, mainly distributed in the cities of Baoji, Weinan, and Xianyang. The effects of artificial factors on reversing this deteriorating trend in the region should be noted. 2) The factors with the greatest influences on vegetation cover changes were popular tourist attractions, transportation, and urbanization rates. The influences of various factors on vegetation cover showed temporal variation, driven by societal and economic development, indicating the complexity and diversity of the influences of anthropogenic factors on vegetation cover. 3) Sustainable development should be promoted and the pressure on the ecology resulting from popular tourist attractions, the transportation network, and rapid urbanization should be reduced.

Abstract Background The rapidly increasing case reports revealed that neuronal intranuclear inclusion disease (NIID) had concomitant other system symptoms besides nervous system symptoms. In this study, we systematically evaluated the symptoms, signs, auxiliary examination, and pathological changes in different systems in NIID patients. Methods NIID patients were confirmed by examining GGC repeats in the NOTCH2NLC gene. Clinical data of NIID patients including symptoms, signs, and auxiliary examinations were collected for analysis. Ubiquitin and p62 were detected in different tissues from previous surgical samples. Results Fifty‐one NIID patients from 17 families were included in this study. Except neurological symptoms, clinical manifestations from other systems were very notable and diverse. The proportions of different system symptoms were 88.2% in nervous system, 78.4% in respiratory system, 72.5% in circulatory system, 72.5% in locomotor system, 66.7% in urinary system, 64.7% in digestive system, 61.5% in reproductive system, and 50.0% in endocrine system. In addition, other common symptoms included sexual dysfunction (43.1%), pupil constriction (56.9%), blurred vision (51.0%), and hearing loss (23.5%). Ubiquitin and p62‐positive cells were found in different tissues and systems in 24 NIID patients with previous surgery. Initial symptoms of NIID and median onset age in different systems also revealed system heterogeneity of NIID. Interpretation For the first time, we systematically demonstrated that NIID is a heterogeneous and systemic neurodegenerative disease by providing clinical and pathological evidence. In addition to the nervous system, the clinical symptomatic and pathological spectrum of NIID has been extended to almost all systems.

Introduction: Prostate cancer (PCa) is dependent on coupled androgen-androgen receptor (AR) signaling for growth and progression. Significant efforts have been made in this research field, as hormonal therapies have greatly improved the survival of patients with metastatic PCa (mPCa). The drug treatment agent JQ1, which potently abrogates bromodomain 4 (BRD4) localization to the AR target loci and therefore significantly impairs AR-mediated gene transcription, is a potent therapeutic option for patients with advanced PCa. In this study, we aimed to investigate the inhibitory effect of JQ1 combined with docetaxel on PCa cells in vitro for the first time. Furthermore, the 3D spheroid culture system was modeled to more accurately simulate the response of PCa cells to drugs.Methods: We established and measured 3D LNCaP spheroids in vitro in order to evaluate the susceptibility of 2D- and 3D-cultured LNCaP cells exposed to the same anti-cancer drug.Results: We demonstrated that JQ1 was an effective drug for promoting cell inhibition after docetaxel treatment in 2D- and 3D- cultured LNCaP cells. Inhibition of 3D cultured formation in the combined treatment group was significantly higher than that in docetaxel or JQ1 alone. Under the same conditions of drug solubility, the drug resistance of 3D spheroids was significantly higher than that of 2D cells. Moreover, dmax and lg volume were suitable parameters for LNCaP cells/spheroid size displaying and evaluating cell viability.Conclusion: 3D cultured spheroids of PCa are an effective tool for studying PCa drug trials. JQ1 combined with docetaxel may be an effective treatment for advanced PCa. This combination therapy strategy deserves further evaluation in clinical trials.

Cell-free DNA (cf-DNA) has been reported to represent a suitable material for liquid biopsy in the diagnosis and prognosis of various cancers. We performed a meta-analysis of published data to investigate the diagnostic value of cf-DNA for renal cancer (RCa). Systematic searches were conducted using Pubmed, Embase databases, Web of Science, Medline and Cochrane Library to identify relevant publications until the 31st March 2021. For all patients, we evaluated the true diagnostic value of cf-DNA by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature. In total, 8 studies, featuring 754 RCa patients, and 355 healthy controls, met our inclusion criteria. The overall diagnostic sensitivity and specificity for cf-DNA was 0.71 (95% confidence interval (CI), 0.55–0.83) and 0.79 (95% CI, 0.66–0.88), respectively. The pooled positive likelihood ratio and pooled negative likelihood ratio were 3.42 (95% CI, 2.04–5.72) and 0.36 (95% CI, 0.23–0.58), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79–0.85), and the diagnostic odds ratio was 7.80 (95% CI, 4.40–13.85). Collectively, our data demonstrate that cf-DNA has high specificity and sensitivity for diagnosing RCa. Therefore, cf-DNA is a useful biomarker for the diagnosis of RCa.

Abstract Background Vitamin B1 (VB1) is a crucial dietary nutrient and essential cofactor for several key enzymes in the regulation of cellular and metabolic processes, and more importantly in the activation of immune system. To date, the precise role of VB1 in Mycobacterium tuberculosis remains to be fully understood. Results In this study, the transcriptional and metabolic profiles of VB1-treated Mycobacterium. bovis BCG were analyzed by RNA-sequencing and LC-MS (Liquid chromatography coupled to mass spectrometry). The selection of BCG strain was based on its common physiological features shared with M. tuberculosis. The results of cell growth assays demonstrated that VB1 inhibited the BCG growth rate in vitro. Transcriptomic analysis revealed that the expression levels of genes related to fatty acid metabolism, cholesterol metabolism, glycolipid catabolism, DNA replication, protein translation, cell division and cell wall formation were significantly downregulated in M. bovis BCG treated with VB1. In addition, the metabolomics LC-MS data indicated that most of the amino acids and adenosine diphosphate (ADP) were decreased in M. bovis BCG strain after VB1 treatment. Conclusions This study provides the molecular and metabolic bases to understand the impacts of VB1 on M.bovis BCG.

Abstract Background The pro-oncogenic anterior gradient 2 (AGR2) is involved in tumor growth and drug resistance of breast cancer. Mechanisms that regulate expression of AGR2 still need to be elucidated. Methods In this study, expression levels of AGR2 and miR-135b-5p were analyzed in different breast cancer cell lines as well as in clinical breast cancer tissues. The in vitro and in vivo functional effect of AGR2 and miR-135b-5p were also investigated. A luciferase reporter assay was applied to confirm the interaction between miR-135b-5p and AGR2 mRNA. Results We identified AGR2 as a target of miR-135b-5p. Expression of AGR2 was up-regulated in doxorubicin-resistant breast cancer cells. AGR2 mediated doxorubicin-sensitivity of breast cancer cells both in vitro and in vivo. miR-135b-5p negatively regulated AGR2-expression of breast cancer cells increasing doxorubicin-sensitivity. However, miR-135b-5p was down-regulated in doxorubicin-resistant breast cancer cells as well as during treatment with doxorubicin, which might be a probable reason for over-expression of AGR2. Up-regulation of miR-135b-5p increased doxorubicin-sensitivity of breast cancer cells in vivo. In addition, levels of AGR2 negatively correlated with levels of miR-135b-5p in clinical breast cancer tissue samples. Conclusion Our results highlight the potential of miR-135b-5p as a target for treating AGR2-expressing breast cancer with doxorubicin-resistance.

Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A1, phospholipase A2, and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival.

Vitamins are essential nutrients and key cofactors of enzymes that regulate cellular metabolism, and also activate the immune system. Recent studies have shown that vitamin B1 (VB1) and vitamin C (Vc) can inhibit Mycobacterium tuberculosis growth, but the precise mechanism is still not well understood. In the present study, we have used RNA-sequencing (RNA-seq), liquid chromatography coupled to mass spectrometry (LC-MS) and single-molecule real-time (SMRT) sequencing to analyze the transcriptional, metabolic and methylation profiles of Mycobacterium bovis BCG when treated with VB1 and Vc. Our results show that, after vitamin treatment, variant metabolites were mainly clustered in pathways related to amino acid metabolism. Treatment with both vitamins significantly up-regulated the gene encoding cysteine synthase A. Additionally, only BCG that was treated with VC showed m4c modifications. Genes harboring this methylation were up-regulated, suggesting that m4c methylation can promote gene transcription to some extent. Overall, this study contributes to the understanding of the effects of VB1 and VC, and suggests that these vitamins constitute potential anti-tuberculosis drugs.

Abstract The discovery and creation of biocatalysts for plant biomass conversion are essential for industrial demand and scientific research of the plant cell wall. α-1,2 and α-1,3-l-arabinofuranosidases are debranching enzymes that catalyzing hydrolytic release of α-l-arabinofuranosyl residues in plant cell wall. Gene database analyses shows that GH62 family only contains specific α-l-arabinofuranosidases that play an important role in the degradation and structure of the plant cell wall. At present, there are only 22 enzymes in this group has been characterized. In this study, we cloned a novel α-1,3-arabinofuranosidase gene (poabf62a) belonging to glycoside hydrolase family 62 from Penicillium oxalicum sp. 68 and expressed it in Pichia pastoris. The molecular mass of recombinant PoAbf62A was estimated to be 32.9 kDa. Using p-nitrophenyl-α-l-arabinofuranoside (pNPαAbf) as substrate, purified PoAbf62A exhibited an optimal pH of 4.5 and temperature of 35 °C. Results of methylation and 13C NMR analyses showed that PoAbf62A was exclusively α-1,3-arabinofuranosidase, specific for cleavage of α-1,3-arabinofuranosyl residues, and with the absence of activity towards α-1,2-arabinofuranose and α-1,5-arabinofuranose. Therefore, PoAbf62A exhibits high activity on sugar beet arabinan and wheat arabinoxylan, because their branched side chain are decorated with α-1,3-arabinofuranose. On the other hand, there is a lack of activity with linear-α-l-1,5-arabinan and xylan that only contained α-l-1,5-arabinofuranose or β-1,4-xylose. The α-1,3-arabinofuranosidase activity identified here provides a new biocatalytic tool to degrade hemicellulose and analyze the structure of plant cell walls.

The American cockroach (Periplaneta americana) is an hemimetabolous insect with rapid growth, high fecundity, and remarkable tissue-regeneration capability. Here Li et al sequence its 3.38-Gb genome and perform the functional studies, yielding insights into its environmental adaptation and developmental plasticity.

‘Dancong’ tea is a famous traditional Oolong tea. In order to keep the original taste of “ancient tea trees”, most of the ‘Dancong’ tea plants are planted in a single plant pattern without pruning. The objective of this study was to explore the effects of long-term non-pruning on main quality constituents in ‘Dancong’ tea. The results showed that the contents of free amino acids, chlorophylls, and floral-honey aromatic substances in tea leaves of unpruned tea plants were higher than those in every year pruned tea plants, while the catechin content in leaves of pruned tea plants was higher than that in leaves of unpruned tea plants. Quantitative proteomics analysis showed that most enzymes involved in biosynthesis of catechins were downregulated in leaves of unpruned tea plants. Five proteins involved in chlorophyll metabolism and 12 proteins related to photosynthesis were upregulated, and the results suggested that higher chlorophyll content and more efficient photosynthetic energy conversion may be important for the higher accumulation of special quality components in leaves of unpruned tea plants. The findings of this study will advance our understanding of the mechanism of formation of different metabolites in leaves of unpruned and pruned tea plants.

Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome-associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome-associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel-sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture.

Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an anti-fibrotic compound available for the treatment of idiopathic pulmonary fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were cultured in the absence and presence of pirfenidone. Cell proliferation was measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell motility was monitored by live cell imaging. Cytotoxicity and cell viability were analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) assays. Gene expression of fibrosis markers was determined by quantitative reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) signaling was analyzed by Western blotting and type I collagen protein expression additionally by immunofluorescence microscopy. Pirfenidone dose-dependently inhibited p-hIF proliferation and motility, without inducing cell death. Pirfenidone suppressed mRNA levels of genes that contribute to extracellular matrix production, as well as basal and TGF-β1-induced collagen I protein production, which was associated with inhibition of the rapamycin-sensitive mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of intestinal fibroblasts and suppresses collagen I production through the TGF-β1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis.

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which mainly causes pulmonary injury and tubercles. Although macrophages are generally considered to harbor the main cells of M. tuberculosis, new evidence suggests that neutrophils are rapidly recruited to the infected lung. M. tuberculosis itself, or its early secreted antigenic target protein 6 (ESAT-6), can induce formation of neutrophil extracellular traps (NETs). However, NETs trap mycobacteria but are unable to kill them. The role of NETs’ formation in the pathogenesis of mycobacteria remains unclear. Here, we report a new M. tuberculosis extracellular factor, bifunctional enzyme Rv0888, with both nuclease and sphingomyelinase activities. Rv0888 sphingomyelinase activity can induce NETs’ formation in vitro and in the lung of the mice and enhance the colonization ability of Mycobacterium smegmatis in the lungs of mice. Mice infected by M. smegmatis harboring Rv0888 sphingomyelinase induced pathological injury and inflammation of the lung, which was mainly mediated by NETs, induced by Rv0888 sphingomyelinase, associated protein (myeloperoxidase) triggered caspase-3. In summary, the study sheds new light on the pathogenesis of mycobacteria and reveals a novel target for TB treatment.

This paper is devoted to the study of the pricing of European options under a non-Gaussian model. This model follows a non-extensive statistical mechanics which can better describe the fractal characteristics of price movement in the financial market. Moreover, we present a simple but precise least-square method for approximation and obtain a closed-form solution of the price of European options. The advantages of this technique are illustrated by numerical simulation, which shows that the least-squares method is better compared with Borland’s two methods in 2002 and 2004.

BackgroundFossil species that can be conclusively identified as stem-relatives of stick- and leaf-insects (Phasmatodea) are extremely rare, especially for the Mesozoic era. This dearth in the paleontological record makes assessments on the origin and age of the group problematic and impedes investigations of evolutionary key aspects, such as wing development, sexual size dimorphism and plant mimicry.Methodology/principal findingsA new fossil insect species, Cretophasmomima melanogramma Wang, Béthoux and Ren sp. nov., is described on the basis of one female and two male specimens recovered from the Yixian Formation (Early Cretaceous, ca. 126±4 mya; Inner Mongolia, NE China; known as 'Jehol biota'). The occurrence of a female abdominal operculum and of a characteristic 'shoulder pad' in the forewing allows for the interpretation of a true stem-Phasmatodea. In contrast to the situation in extant forms, sexual size dimorphism is only weakly female-biased in this species. The peculiar wing coloration, viz. dark longitudinal veins, suggests that the leaf-shaped plant organ from the contemporaneous 'gymnosperm' Membranifolia admirabilis was used as model for crypsis.Conclusions/significanceAs early as in the Early Cretaceous, some stem-Phasmatodea achieved effective leaf mimicry, although additional refinements characteristic of recent forms, such as curved fore femora, were still lacking. The diversification of small-sized arboreal insectivore birds and mammals might have triggered the acquisition of such primary defenses.

The protection and inheritance of the local intangible cultural heritage (ICH) holds profound significance, which has the characteristics of oral transmission and the intertwining of time and space, is an important content and means of rural cultural governance in China in the new era. It is significant in value for promoting rural revitalization and passing on the cultural genes of China. As rural society transforms, the change of rural social structure and cultural order leads to some conflicts for rural ICHs in China, such as subjective crises, weakening of values and the impact of modernity. Therefore, this paper combines the advantages of experience with the inheritance needs of ICH and puts its inheritance and protection under the national strategy of rural revitalization. The study focuses on the function of ICH in rural revitalization from the perspective of experience and explores the topic from three levels: the government, universities, and villages. Moreover, we provide sustainable development strategies for integrating intangible cultural heritage into rural revitalization to promote the revival of rural culture. This article explores the mutually beneficial relationship between intangible cultural heritage and rural revitalization, enhancing our understanding of both aspects. The primary contribution lies in providing sustainable development strategies for integrating intangible cultural heritage into rural revitalization at the government, university, and village levels. Ochrona i dziedziczenie lokalnego niematerialnego dziedzictwa kulturowego (ICH) ma ogromne znaczenie, gdyż łączy przekaz ustny z elementami czasu i przestrzeni. Jest ważną formą treści kulturowych a także sposobem zarządzania kulturą na obszarach wiejskich w Chinach w nowej epoce. Ma ogromną wartość dla promowania rewitalizacji obszarów wiejskich i przekazywania genów kulturowych Chin. W miarę transformacji społeczeństwa wiejskiego zmiana struktury społecznej obszarów wiejskich i porządku kulturowego prowadzi do pewnych konfliktów dla wiejskich ICH w Chinach, takich jak kryzysy subiektywne, osłabienie wartości i wpływ nowoczesności. Niniejszy artykuł łączy doświadczenia z potrzebami spadkowymi ICH i wpisuje jego dziedziczenie i ochronę w krajową strategię rewitalizacji obszarów wiejskich. Badanie koncentruje się na funkcji ICH w rewitalizacji obszarów wiejskich z perspektywy doświadczenia i eksploruje temat na trzech poziomach: rządu, uniwersytetów i wsi. Ponadto sugerujemy strategie zrównoważonego rozwoju mające na celu włączenie niematerialnego dziedzictwa kulturowego do rewitalizacji obszarów wiejskich w celu promowania odrodzenia kultury wiejskiej. [ABSTRACT FROM AUTHOR]