Search

Abstract Objective Cancer is a predominant cause of death globally. PHD-finger domain protein 5 A (PHF5A) has been reported to participate in various cancers; however, there has been no pan-cancer analysis of PHF5A. This study aims to present a novel prognostic biomarker and therapeutic target for cancer treatment. Methods This study explored PHF5A expression and its impact on prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), functional status and tumor immunity across cancers using various public databases, and validated PHF5A expression and its correlation with survival, immune evasion, angiogenesis, and treatment response in hepatocellular carcinoma (HCC) using bioinformatics tools, qRT-PCR and immunohistochemistry (IHC). Results PHF5A was differentially expressed between tumor and corresponding normal tissues and was correlated with prognosis in diverse cancers. Its expression was also associated with TMB, MSI, functional status, tumor microenvironment, immune infiltration, immune checkpoint genes and tumor immune dysfunction and exclusion (TIDE) score in diverse malignancies. In HCC, PHF5A was confirmed to be upregulated by qRT-PCR and IHC, and elevated PHF5A expression may promote immune evasion and angiogenesis in HCC. Additionally, multiple canonical pathways were revealed to be involved in the biological activity of PHF5A in HCC. Moreover, immunotherapy and transcatheter arterial chemoembolization (TACE) worked better in the low PHF5A expression group, while sorafenib, chemotherapy and AKT inhibitor were more effective in the high expression group. Conclusions This study provides a comprehensive understanding of the biological function of PHF5A in the carcinogenesis and progression of various cancers. PHF5A could serve as a tumor biomarker related to prognosis across cancers, especially HCC, and shed new light on the development of novel therapeutic targets.

Abstract The G‐protein‐coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1‐Gi complexes in synthetic agonist‐bound forms have been resolved to date. However, the commercial drug recognition and Gq coupling mechanisms of CB1 remain elusive. Herein, the cryo‐electron microscopy (cryo‐EM) structure of CB1‐Gq complex, in fenofibrate‐bound form, at near‐atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and Gq protein coupling by CB1 and will facilitate future drug discovery and design.

BackgroundStudies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC.MethodThis retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital.ResultsTwenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3–4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea.ConclusionOsimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Summary: Skeletal muscle function declines in the aging process or disease; however, until now, skeletal muscle has remained one of the organs most undertreated with medication. In this study, naringenin (NAR) was found to build muscle endurance in wild-type mice of different ages by increasing oxidative myofiber numbers and aerobic metabolism, and it ameliorates muscle dysfunction in mdx mice. The transcription factor Sp1 was identified as a direct target of NAR and was shown to mediate the function of NAR on muscle. Moreover, the binding site of NAR on Sp1 was further validated as GLN-110. NAR enhances the binding of Sp1 to the CCCTGCCCTC sequence of the Esrrg promoter by promoting Sp1 phosphorylation, thus upregulating Esrrg expression. The identification of the Sp1-ERRγ transcriptional axis is of great significance in basic muscle research, and this function of NAR has potential implications for the improvement of muscle function and the prevention of muscle atrophy.

Floods and droughts on farmland seriously damage agricultural production. Porous fiber materials (PFM) made from mineral rocks have high porosity, permeability, and water retention and are utilized widely in green roofs and agricultural production. Therefore, studying the impact of PFM on the improvement of farmland is of great importance for soil and water conservation. We set 64 extreme rainfalls to analyze the impact of PFM on soil water content (SWC), runoff, nutrient loss, microorganism, and plant growth. The results showed that PFM can effectively reduce runoff and improve soil water distribution, and enhance the soil water holding capacity. Furthermore, PFM reduced the loss of nitrogen and phosphorus by 18.3% to 97% in the runoff, and the soil erosion of summer corn was more strongly influenced by lower vegetation cover, compared with winter wheat. Finally, when PFM was buried in the soil, the wheat yield increased by −6.7%–20.4%, but the corn yield in some PFM groups decreased by 5.1% to 42.5% under short-duration irrigation conditions. Our study emphasizes that the effectiveness of PFM depends mainly on the following: First, PFM with high porosity can increase soil water holding capacity and timely replenish the water lost from the surrounding soil. Second, PFM with high permeability can increase infiltration during rainfall and decrease runoff and nutrient loss, reducing the risk of farmland flooding and pollution. Finally, PFM consists of gold ions and alkali metal oxides, which can stabilize agglomerates and improve soil enzyme activity, thereby increasing the relative abundance of some microbial strains and promoting crop growth. However, when the rainfall amount was low or PFM volume was large, PFM could not store water sufficiently during rainfall, which seriously reduced the maximum saturated moisture content and water absorption performance. Meanwhile, the PFM could not release water in time and replenish the soil water deficit, which increased drought risk. In conclusion, the appropriate volume of PFM and irrigation system may enhance soil water storage capacity, minimize agricultural pollution, and promote crop production.

Measurement(s) distributed global population and water withdrawal Technology Type(s) mathematical statistics and analysis

The cold regions of China (CRC) are important and vulnerable freshwater recharge areas on land, and any changes in them are related to the survival of millions of people in East Asia. However, for nearly half a century, in cold regions, the extreme temperature response to global warming is still poorly understood. In this study, we systematically studied the temperature extreme changes in cold regions of China since 1961 and discussed the possible circulation factors in detail. The results showed that 1) the warming magnitudes in cold nights and warm nights are greater than those in cold days and warm days, and decreases in cold nights and cold days and increases in warm days and warm nights appeared in almost all of cold regions of China. Most of the temperature indices displayed the largest magnitudes of warming in winter. 2) Spatially, for most of the temperature extremes, the stations located at Qinghai–Tibet Plateau (TPC) and Northwest China (NWC) showed a larger warming trend than that shown by the station at Northeast China (NEC). 3) The responses of temperature extremes at different cold regions to each circulation index are variable. Atlantic Multidecadal Oscillation (AMO) has a significant relationship with almost all the indices in cold regions of China. Almost all the temperature extremes of TPC and NWC showed closely relationship with the North Atlantic Oscillation (NAO), especially for diurnal temperature range (DTR), daily maximum temperature, and the cold extremes. Multivariate ENSO Index (MEI) is significantly related to most the temperature indices of Northwest China and Northeast China. However, MEI has a significant impact on only TPC’s diurnal temperature range and warmest night (TNx). 4) Atlantic Multidecadal Oscillation displayed significant relationships with most the temperature extremes in every season in cold regions of China. However, the summer and winter MEI and the summer and winter North Atlantic Oscillation showed significant impacts on only diurnal temperature range, daily minimum temperatures (TNm), and TNx.

BackgroundMembrane palmitoylated proteins (MPPs) are engaged in various biological processes, such as cell adhesion and cell polarity. Dysregulated MPP members have different effects on hepatocellular carcinoma (HCC) development. However, the role of MPP6 in HCC has been unknown.MethodHCC transcriptome and clinical data from different public databases were downloaded and analyzed, and the results were further validated by qRT−PCR, Western blotting and immunohistochemistry (IHC) using HCC cell lines and tissues. The association between MPP6 and prognosis, potential pathogenic mechanisms, angiogenesis, immune evasion, tumor mutation burden (TMB) and treatment response in HCC patients was analyzed by bioinformatics and IHC staining.ResultsMPP6 was significantly overexpressed in HCC, and its expression was related to T stage, pathologic stage, histologic grade and adverse prognosis in HCC patients. Gene set enrichment analysis revealed that differentially expressed genes were mainly enriched in the synthesis of genetic materials and the WNT signaling pathway. GEPIA database analysis and IHC staining suggested that MPP6 expression had a positive correlation with angiogenesis. Single-cell dataset analysis indicated that MPP6 was associated with features of the tumor microenvironment. Additional analyses discovered that MPP6 expression was inversely related to immune cell infiltration and was involved in tumor immune evasion. MPP6 expression was positively associated with TMB, and patients with high TMB had an adverse prognosis. Immunotherapy was more effective in HCC patients with low MPP6 expression, whereas those with high MPP6 expression responded better to sorafenib, gemcitabine, 5-FU, and doxorubicin.ConclusionsElevated MPP6 expression is associated with an unfavorable prognosis, angiogenesis and immune evasion in HCC. Moreover, MPP6 has the potential to be used to assess TMB and treatment response. Therefore, MPP6 might serve as a novel prognostic biomarker and therapeutic target for HCC.

Summary: Muscle stem cells, called satellite cells (SCs), are employed to repair and rebuild muscle. SC-based therapeutic strategies are urgently needed. In this study, we showed that Lycium barbarum extract (LBE) improved the number of SCs and enhanced muscle regeneration by promoting SC activation and self-renewal in both adult and aging mice. L. barbarum polysaccharide (LBP), the main component of LBE, also played a similar role. More importantly, LBP1C-2, a homogeneous polysaccharide isolated from LBP, was uncovered to be an active component in regulating SC function. Mechanism study revealed that LBP1C-2 might bind to FGFR1 to activate SCs and promote SC self-renewal through Spry1 upregulation. This might be the first study to show that LBE participated in the regulation of SCs, and the active components and targets of LBE were identified. This study lays a theoretical foundation for the medicinal or auxiliary medicinal use of L. barbarum in skeletal muscle.

Abstract Background Plastome-scale data have been prevalent in reconstructing the plant Tree of Life. However, phylogenomic studies currently based on plastomes rely primarily on maximum likelihood inference of concatenated alignments of plastid genes, and thus phylogenetic discordance produced by individual plastid genes has generally been ignored. Moreover, structural and functional characteristics of plastomes indicate that plastid genes may not evolve as a single locus and are experiencing different evolutionary forces, yet the genetic characteristics of plastid genes within a lineage remain poorly studied. Results We sequenced and annotated 10 plastome sequences of Gentianeae. Phylogenomic analyses yielded robust relationships among genera within Gentianeae. We detected great variation of gene tree topologies and revealed that more than half of the genes, including one (atpB) of the three widely used plastid markers (rbcL, atpB and matK) in phylogenetic inference of Gentianeae, are likely contributing to phylogenetic ambiguity of Gentianeae. Estimation of nucleotide substitution rates showed extensive rate heterogeneity among different plastid genes and among different functional groups of genes. Comparative analysis suggested that the ribosomal protein (RPL and RPS) genes and the RNA polymerase (RPO) genes have higher substitution rates and genetic variations among plastid genes in Gentianeae. Our study revealed that just one (matK) of the three (matK, ndhB and rbcL) widely used markers show high phylogenetic informativeness (PI) value. Due to the high PI and lowest gene-tree discordance, rpoC2 is advocated as a promising plastid DNA barcode for taxonomic studies of Gentianeae. Furthermore, our analyses revealed a positive correlation of evolutionary rates with genetic variation of plastid genes, but a negative correlation with gene-tree discordance under purifying selection. Conclusions Overall, our results demonstrate the heterogeneity of nucleotide substitution rates and genetic characteristics among plastid genes providing new insights into plastome evolution, while highlighting the necessity of considering gene-tree discordance into phylogenomic studies based on plastome-scale data.

Understanding the pattern of species extinction risk is key to biodiversity conservation. Previous studies showed extinction risk correlates strongly with taxon species richness. However, there is no consistent conclusion to this hypothesis, and patterns differ among different taxonomic groups. Here, we collated lists of vascular plant and terrestrial vertebrate species information on their threatened status in Yunnan Province and performed the first systematical analysis to test the relationship between the proportion of threatened or extinct species and species richness at the family-level of the two above taxa in Yunnan Province, China. We found that extinction risk was not randomly distributed among families and the estimated extinction risk was higher among closer phylogenetic families than expected by chance. Moreover, there were significant negative correlations between extinction risk and family size in vascular plants and terrestrial vertebrates. Our results suggest that family size is a good predictor of extinction risk and extinction risk is related to evolutionary history at family-level among vascular plants and terrestrial vertebrates in Yunnan.

Background and Objectives: A prognosis for kids with pediatric dilated cardiomyopathy (PDCM) is urgently needed to identify high-risk patients. This study aimed to determine the association of levels and soluble suppression of tumorigenicity 2 (sST2) and medical therapy of β-blocker inhibitors with the risk of adverse events in PDCM. Materials and Methods: A total of 124 patients with PDCM were enrolled after admission from 2 centers in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). Based on a median sST2 level and the usage of β-blocker inhibitors, patients were divided into four groups. The Cox proportional hazard model was used to assess the risk of incident adverse events. Results: The median level of sST2 was 23.77 ng/mL, and 53 (42.7%) patients received β-blocker treatment. Over a median follow-up of 678 days, 37 (29.8%) adverse events occurred. Compared with patients with sST2 < median and without β-blocker, patients with sST2 ≥ median and without β-blocker (HR: 7.01; 95% CI: 1.21–40.45), followed by those with sST2 ≥ median and use of β-blocker had the highest risk of adverse events (hazard ratio (HR): 5.51; 95% confidence interval (CI): 1.17–25.84). However, a significant association was not observed in patients with sST2 < median and use of β-blocker. These associations were consistent across different subgroups. Conclusions: A higher level of sST2 was associated with a higher risk of adverse events in patients with PDCM, and β-blocker treatment for children with high levels of sST2 can effectively avoid adverse events.

The precision rotary vector reducer with involute variable tooth thickness (PRVT) is a high-performance precision transmission device, which is very suitable for aerospace, medical machinery, industrial robots, automation equipment, and other fields, and its torsional stiffness is an important performance index. This paper establishes a dynamics model of the whole machine based on the Lagrangian method by considering gear meshing stiffness, damping, and machining errors, and the influence of different machining errors on dynamic torsional stiffness is studied. The results show that increasing the distribution circle radius error of the crankshaft, the crank angle error and the distribution circle radius error of the crankshaft bearing hole on the carrier will cause the peak-to-peak torsional stiffness to increase. Therefore, the machining errors should be controlled within a reasonable range to improve the whole machine’s stability. An increase in the crankshaft bearing hole rotation error on the No. 1 beveloid gear has no notable impact on the peak-to-peak value and the average value of the torsional stiffness. Similarly, the rotation angle error of the crankshaft bearing hole on the No. 1 carrier has no significant effect on the torsional stiffness. The research results provide a useful reference for the torsional stiffness analysis of PRVT.

Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept ''Redox-stress Response Capacity (RRC)'', which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging. Keywords: Oxidative stress, Aging, Redox, Redox-stress Response Capacity, RRC

Sorbaria arborea is a species which is endemic to China. We utilized next-generation Illumina sequencing technology to sequence and assemble its chloroplast genome. The 160,137 bp genome contained four main sections, including a pair of inverted repeat regions which were 26,332 bp in length, and a small single-copy region was 19,418 bp, as well as a large single-copy region, which was 88,055 bp. The genome had a GC content of 36.1% and contained 113 unique genes, including 4 rRNAs, 30 tRNAs, and 79 protein-coding genes. The phylogenetic relationship of 25 Rosaceae species was constructed based on their chloroplast genome sequences, which supported a close relationship between S. arborea and Amygdaloideae. This newly sequenced plastid genome provides useful information for assessing the genetic diversity and phylogenetic position of S. arborea.

Wave is a common environmental load that often causes serious damages to offshore structures. In addition, the stability for the submarine artificial slope is also affected by the wave loading. Although the landslide of submarine slopes induced by the waves received wide attention, the research on the influence of solitary wave is rare. In this study, a 2-D integrated numerical model was developed to investigate the stability of the foundation trench under the solitary wave loading. The Reynolds-averaged Stokes (RANS) equations were used to simulate the propagation of a solitary wave, while the current was realized by setting boundary inlet/outlet velocity. The pore pressure induced by the solitary wave was calculated by Darcy’s law, and the seabed was characterized by Mohr–Coulomb constitutive model. Firstly, the wave model was validated through the comparison between analytical solution and experimental data. The initial consolidation state of slope under hydrostatic pressure was achieved as the initial state. Then, the factor of stability (FOS) for the slope corresponding to different distances between wave crest and slope top was calculated with the strength reduction method. The minimum of FOS was defined as the stability index for the slope with specific slope ratio during the process of dynamic wave loading. The parametric study was conducted to examine the effects of soil strength parameters, slope ratio, and current direction. At last, the influence of upper slope ratio in a two-stage slope was also discussed.

In this paper, a distributed economic dispatch scheme considering power limit is proposed to minimize the total active power generation cost in a droop-based autonomous direct current (DC) microgrid. The economical dispatch of the microgrid is realized through a fully distributed hierarchical control. In the tertiary level, an incremental cost consensus-based algorithm embedded into the economical regulator is utilized to search for the optimal solution. In the secondary level, the voltage regulator estimating the average voltage of the DC microgrid is used to generate the voltage correction item and eliminate the power and voltage oscillation caused by the deviation between different items. Then, the droop controller in the primary level receives the reference values from the upper level to ensure the output power converging to the optimum while recovering the average voltage of the system. Further, the dynamic model is established and the optimal communication network topology minimizing the impact of time delay on the voltage estimation is given in this paper. Finally, a low-voltage DC microgrid simulation platform containing different types of distributed generators is built, and the effectiveness of the proposed scheme and the performance of the optimal topology are verified.

The complete chloroplast genome of Poikilospermum lanceolatum was sequenced using HiSeq4000 of Illumina. The length of this genome was 153, 454 bp, including a large single copy (LSC) region (84,202 bp), a small single copy (SSC) region (18,172 bp), and two inverted repeat (IR) regions (25,540 bp). The overall GC content of the genome of P. lanceolatum was 36.9%. The genome included 111 unique genes (78 protein-coding genes, 29 tRNA genes, and four rRNA genes). Phylogenetic analysis based on 67 protein-coding genes showed that Boehmerieae was sister to P. lanceolatum, with 100% bootstrap values.

In this study, the major winter wheat planting area of China is selected as the study area, with the time scale of the growth period of winter wheat (a total of 56 growth periods during October 1961 to May 2016). The significance, stability, magnitude of the trend and the average trend of the study area with eight temperature indices and seven precipitation indices of 453 meteorological stations are tested by Mann−Kendall method and Sen’s nonparametric method. The following observation can be made: (1) the cold extreme indices show strong and stable downward trend in most of the stations in the study area, while the hot extreme indices show a strong and stable upward trend, especially in the northern winter wheat planting area and the north of the southern winter wheat planting area. (2) The trends of extreme precipitation indices in most of the sites in the study area are insignificant and unstable. Only in R20mm, a significant and stable decreasing trend is shown in some stations, which is mainly located in the northern winter wheat planting area and part of the central and western regions in the study area. The results in some ways could enrich the references for understanding the climate change in the growth period of winter wheat in the region and help to formulate a better agronomic management practice of winter wheat.

A microgrid with low-voltage ride-through capability is designed. The designed microgrid avoids operating in unplanned islanded mode during an asymmetric ground fault which occurs in the low voltage distribution network and supports fault recovery for distribution network. Furthermore, compared with the traditional microgrid topology, the proposed microgrid topology also saves a lot of power electronic devices. The simulation results with PSCAD/EMTDC show that the microgrid can keep the distributed generations and loads operate normally when an asymmetric ground fault occurs in the low voltage distribution grid. It can also increase the active power output according to the requirement of the distribution network to support the distribution network fault recovery.

Boldness is closely related to fish species' adaptative strategies and invasiveness and has become the focus of fish personality research. However, due to the lack of studies on behavioral stages, the ecological functions of certain behaviors remain unclear. To better understand the link between boldness and invasiveness in stone moroko (Pseudorasbora parva), an invasive Asian fish species, we exposed the fish to an open-field environment for 60 min and assessed their behavioral patterns, profiles, and stages. The results show that the boldness behavior of stone moroko was characterized by high activity, low average velocity, and diverse swimming postures. Five behavioral stages with significant differences were revealed: outbreak, inhibition, slow swimming, exploration, and adaptation. These observations suggest that stone moroko can quickly habituate to new environments. In addition, stone moroko spent more energy on exploring the living area and less on environmental risk assessment, as revealed by an analysis of their energy trade-off strategy. The behavioral strategies of stone moroko may explain their extremely high environmental adaptability and ability to invade multiple environments. [ABSTRACT FROM AUTHOR]