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Objective. Hyperuricemia (HUA) is a common metabolic disease caused by disordered purine metabolism. We aim to reveal the mechanisms underlying the anti-HUA function of Simiao pill and provide therapeutic targets. Methods. Simiao pill-related targets were obtained using Herbal Ingredients’ Targets (HIT), Traditional Chinese Medicine Systems Pharmacology (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID). HUA-associated targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, ggraph and igraph R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfiler. The top 10 core targets were identified through cytoHubba. Molecular docking was conducted using PyMOL and AutoDock high-performance liquid chromatograph (HPLC) analysis was performed to identify effective compounds of Simiao pill. Results. Simiao pill-HUA target network contained 80 targets. The key targets were mainly involved in inflammatory responses. Insulin (INS), tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin 1 beta (IL1B), vascular endothelial growth factor A (VEGFA), leptin (LEP), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine ligand 2 (CCL2), interleukin-10 (IL10), and toll like receptor 4 (TLR4) were the top 10 targets in the PPI network. GO analysis demonstrated the main implication of the targets in molecular responses, production, and metabolism. KEGG analysis revealed that Simiao pill might mitigate HUA through advanced glycation end-product- (AGE-) receptor for AGE- (RAGE-) and hypoxia-inducible factor-1- (HIF-1-) associated pathways. IL1B, IL6, IL10, TLR4, and TNF were finally determined as the promising targets of Simiao pill treating HUA. Through molecular docking and HPLC analysis, luteolin, quercetin, rutaecarpine, baicalin, and atractylenolide I were the main active compounds. Conclusions. Simiao pill can mitigate HUA by restraining inflammation, mediating AGE-RAGE- and HIF-1-related pathways, and targeting IL1B, IL6, IL10, TLR4, and TNF.

Heterologous expression of the designed echinocandin biosynthetic gene cluster in the chassis strain results in the production of two novel tetradeoxy echinocandins, one of which has superior stability and antifungal activity to echinocandin B.

Supplementary Table S1. Hematology measurements for the mice after the treatment with saline, cabazitaxel and dCTX NPs. The blood samples were collected on day 0, 6, 11, and 15 post-administration. The data are presented as the means {plus minus} SD (n = 5).

Taxane-based chemotherapeutics are clinically available as frontline treatment regimens for cervical cancer. However, drug resistance and life-threatening toxicity impair the clinical efficacy of taxanes, so more effective and less toxic therapeutic modalities are urgently needed. Cabazitaxel has attracted increasing interest due to its potential to circumvent the drug resistance by taxanes. We previously showed that tethering docosahexaenoic acid (DHA) to cabazitaxel enabled the prodrug to self-assemble into nanoparticles in water. Despite this encouraging finding, the DHA–cabazitaxel conjugate formulation requires further optimization to enhance nanoparticle retention and tumor delivery. We here integrated this conjugate into amphiphilic poly(ethylene glycol)-block-poly(D,L-lactic acid) copolymers to assemble dCTX NPs. The nanoparticle abrogated P-glycoprotein–mediated resistance in cancer cells. In a docetaxel-resistant cervical tumor xenograft-bearing mouse model, the efficacy was augmented by the nanotherapy when compared with solution-based free drugs (i.e., docetaxel and cabazitaxel). Dose intensification of dCTX NPs markedly suppressed the tumor growth in this model. Detailed studies revealed that systemic toxicity was alleviated, and MTD of dCTX NPs was at least 3 times higher than that of free cabazitaxel in animals, which may enable dose increases for clinical studies. In conclusion, the new formulation addresses essential requirements in terms of the stability, safety, and translational capacity for initiating early-phase clinical trials.

Supplementary Figure S2. The cytotoxicity of dCTX NPs compared with cabazitaxel against cancer cell lines in vitro. Analysis (A) and quantification (B) of apoptosis of HeLa and A549 cells after the treatment with dCTX NPs for 48 h. The drug concentrations used to treat HeLa and A549 cells were 16 and 4 nM, respectively.

Supplementary Figure S1. Chemical structures of paclitaxel, docetaxel, and cabazitaxel.

Supplementary methods for nanonparticle characterization, cell assays and histological analyses of tumors.

Supplementary Figure S3. The cytotoxicity of dCTX NPs compared with cabazitaxel against cancer cell lines in vitro. Analysis (A) and quantification (B) of cell cycle of HeLa and A549 cells after the treatment with dCTX NPs for 48 h. The drug concentrations used to treat HeLa and A549 cells were 8 and 2 nM, respectively.

Supplementary Figure S4. Cellular uptake of dCTX NPs in Hela/DTX cells. The cells were treated with free DiI and DiI@dCTX NPs and visualized by confocal laser scanning microscope (CLSM). The red fluorescent signal represented the DiI dye in cells. The cell lysosomes and nuclei were stained with LysoTracker Green NDN-26 (green) and Hoechst 33342 (blue), respectively. The scale bars represent 20 μm in length.

Supplementary Figure S1.

Purpose: To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer.Experimental Design: The expression patterns of miR-195 and miR-497 were initially examined in breast cancer tissues and cell lines by Northern blotting and quantitative real-time PCR. Combined bisulfite restriction analysis and bisulfite sequencing were carried out to study the DNA methylation status of miR-195 and miR-497 genes. Breast cancer cells stably expressing miR-195 and miR-497 were established to study their role and targets. Finally, normal, fibroadenoma and breast cancer tissues were employed to analyze the correlation between miR-195/497 levels and malignant stages of breast tumor tissues.Results: MiR-195 and miR-497 were significantly downregulated in breast cancer. The methylation state of CpG islands upstream of the miR-195/497 gene was found to be responsible for the downregulation of both miRNAs. Forced expression of miR-195 or miR-497 suppressed breast cancer cell proliferation and invasion. Raf-1 and Ccnd1 were identified as novel direct targets of miR-195 and miR-497. miR-195/497 expression levels in clinical specimens were found to be correlated inversely with malignancy of breast cancer.Conclusions: Our data imply that both miR-195 and miR-497 play important inhibitory roles in breast cancer malignancy and may be the potential therapeutic and diagnostic targets. Clin Cancer Res; 17(7); 1722–30. ©2011 AACR.

Skeletal muscle stem cells (also known as satellite cells [SCs]) are essential for muscle regeneration and the regenerative activities of SCs are intrinsically governed by gene regulatory mechanisms, but the post-transcriptional regulation in SCs remains largely unknown. N(6)-methyladenosine (m6A) modification of RNAs is the most pervasive and highly conserved RNA modification in eukaryotic cells; it exerts powerful impact on almost all aspects of mRNA processing that is mainly endowed by its binding with m6A reader proteins. In this study, we investigate the previously uncharacterized regulatory roles of YTHDC1, an m6A reader in mouse SCs. Our results demonstrate that YTHDC1 is an essential regulator of SC activation and proliferation upon acute injury-induced muscle regeneration. The induction of YTHDC1 is indispensable for SC activation and proliferation; thus, inducible YTHDC1 depletion almost abolishes SC regenerative capacity. Mechanistically, transcriptome-wide profiling using LACE-seq in both SCs and mouse C2C12 myoblasts identifies m6A-mediated binding targets of YTHDC1. Next, splicing analysis defines splicing mRNA targets of m6A-YTHDC1. Furthermore, nuclear export analysis also leads to the identification of potential mRNA export targets of m6A-YTHDC1 in SCs and C2C12 myoblasts;interestingly, some mRNAs can be regulated at both splicing and export levels. Lastly, we map YTHDC1 interacting protein partners in myoblasts and unveil a myriad of factors governing mRNA splicing, nuclear export, and transcription, among which hnRNPG appears to be a bona fide interacting partner of YTHDC1. Altogether, our findings uncover YTHDC1 as an essential factor controlling SC regenerative ability through multifaceted gene regulatory mechanisms in mouse myoblast cells.

There are few studies on the comorbidity of hypertension (HTN), diabetes mellitus (DM) and dyslipidemia (DLP) associated with stroke. We aimed to explore the relationship between the number of metabolic diseases and stroke and its different subtypes, and to reveal whether metabolic diseases alone or coexist can significantly increase the risk of stroke.We completed a multi-center case-control study in Jiangxi Province, China. Neuroimaging examination was done in all cases. Controls were stroke-free adults recruited from the community in the case concentration area and matched with the cases in 1:1 ratio by age and sex. Odds ratios (OR) were calculated by conditional logistic regression.We enrolled 11,729 case-control pairs. The estimated ORs among patients with 1, 2 and 3 metabolic diseases were 3.16 (2.78-3.60), 7.11 (6.16-8.20), 12.22 (9.73-15.36), respectively after adjusting age, body mass index, urban-rural areas, cardiac disease, smoking, alcohol intake, physically active, high intake of salt, meat-biased diet, high homocysteine. The coexistence of HTN and DM (OR: 7.67), the coexistence of HTN and DLP (OR:7.58), and the coexistence of DM and DLP (OR:3.64) can all significantly increase the risk of stroke. HTN alone or combined other metabolic diseases were significantly more strongly associated with intracerebral haemorrhage than ischemic stroke.The risk of stroke increased with the number of chronic metabolic diseases. It is necessary to regularly monitor blood pressure, blood sugar and blood lipids and strengthen lifestyle management and take appropriate drug interventions to prevent exposure to multiple metabolic diseases based on existing conditions.

Asian women have smaller breast sizes and greater breast density, which suggests specific research on their breast kinematics and biomechanics. To investigate vertical breast displacement of Asian women among exercise modalities (rope skipping, walking, jogging, running) in different support conditions (wearing everyday bra or sports bra), and assess the motion between different parts of the breast, seven participants were selected to participate in this study. Five infrared markers were placed on each of their left breasts, and a three-dimensional motion capture system (NDI Optotrak Investigator) was used to collect the data on vertical breast displacement during walking (5 km/h), jogging (7.5 km/h), running (10 km/h) and rope skipping (2 Hz). No significant difference was found in the vertical displacement of different parts of the breast in the two bra conditions. Also, there was significant difference in vertical breast displacement among rope skipping, jogging and running. Breast size did not significantly affect its vertical displacement. The smaller, denser breast appears to reach a threshold of vertical displacement that is similar at high severities of dynamic exercises (jogging, running and rope skipping). The results might be useful for designing special sports bras for Asian women with small breasts or rope skipping participants to improve the shock absorption function.

Different lower limbs and devices used for the contact pressure measurement of the compression stocking make a significant difference to the precise contact pressure value. This study aimed to fabricate a novel soft leg mannequin based on the standard-sized wooden leg mannequin, but closer to the human leg with soft tissue and bones and to evaluate further the performance of the fabricated leg mannequin. The contact pressure exerted by the graduated compression stocking was measured by the fabricated leg mannequin at four different locations along six different cross-sections. Comparing the contact pressure measured by the fabricated leg mannequin, the standard-sized wooden leg mannequin and human legs, the fabricated leg mannequin has a similar pattern to human legs, and contact pressure exerted by the wooden leg mannequin was far higher than that of human legs. In addition, the local contact pressure measured by the fabricated leg mannequin also has a remarkable agreement with that of human legs. Moreover, there was a significant Spearman rank correlation between the contact pressure measured by the fabricated leg mannequin and the human leg. Therefore, the performance of the fabricated leg mannequin can be consistent with the human leg, which enables the fabricated leg mannequin to replace the standard-sized wooden leg mannequin for standard tests.

The electron–hole pairs separated effectively by intermolecular charge transfer between triphenylamine and heptazine of doped g-C3N4 improve photocatalytic hydrogen evolution.

Little is known about three-dimensional (3D) genome organization in skeletal muscle stem cells [also called satellite cells (SCs)]. Here, we comprehensively map the 3D genome topology reorganization during mouse SC lineage progression. Specifically, rewiring at the compartment level is most pronounced when SCs become activated. Marked loss in topologically associating domain (TAD) border insulation and chromatin looping also occurs during early activation process. Meanwhile, TADs can form TAD clusters and super-enhancer–containing TAD clusters orchestrate stage-specific gene expression. Furthermore, we uncover that transcription factor PAX7 is pivotal in enhancer-promoter (E-P) loop formation. We also identify cis-regulatory elements that are crucial for local chromatin organization at Pax7 locus and Pax7 expression. Lastly, we unveil that geriatric SC displays a prominent gain in long-range contacts and loss of TAD border insulation. Together, our results uncover that 3D chromatin extensively reorganizes at multiple architectural levels and underpins the transcriptome remodeling during SC lineage development and SC aging.

Disease risk is a persistent problem in domestic cattle farming, while economic traits are the main concern. This study aimed to reveal the epigenetic basis for differences between zebu (Bos indicus) and taurine cattle (Bos taurus) in disease, disease resistance, and economic traits, and provide a theoretical basis for the genetic improvement of domestic cattle. In this study, whole genome bisulfite sequencing (WGBS) was used to analyze the whole-genome methylation of spleen and liver samples from Yunnan zebu and Holstein cattle. In the genome-wide methylation pattern analysis, it was found that the methylation pattern of all samples was dominated by the CG type, which accounted for >94.9%. The DNA methylation levels of different functional regions and transcriptional elements in the CG background varied widely. However, the methylation levels of different samples in the same functional regions or transcriptional elements did not differ significantly. In addition, we identified a large number of differentially methylation region (DMR) in both the spleen and liver groups, of which 4713 and 4663 were annotated to functional elements, and most of them were annotated to the intronic and exonic regions of genes. GO and KEGG functional analysis of the same differentially methylation region (DMG) in the spleen and liver groups revealed that significantly enriched pathways were involved in neurological, disease, and growth functions. As a result of the results of DMR localization, we screened six genes (DNM3, INPP4B, PLD, PCYT1B, KCNN2, and SLIT3) that were tissue-specific candidates for economic traits, disease, and disease resistance in Yunnan zebu. In this study, DNA methylation was used to construct links between genotypes and phenotypes in domestic cattle, providing useful information for further screening of epigenetic molecular markers in zebu and taurine cattle.

Here, a facile method is reported to prepare multifunctional cotton fabrics with high flame retardancy, high electrical conductivity, superamphiphobicity, and high electromagnetic shielding. The cotton fabric surface was first modified with phytic acid (PA), which promoted dehydration and carbonization of cellulose to increase flame retardancy in the process of pyrolysis. Tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) coating with nanospheres as interlayers created hierarchical roughness that facilitated the construction of superamphiphobic surfaces and provided adhesion sites for silver nanoparticles. In addition, the TA-APTES coating improved flame retardancy because the APTES-containing silicon could form silicon carbon layers to isolate heat and oxygen. Subsequently, the surface energy of the composite cotton fabric was reduced by fluorine-containing molecules. The prepared composite cotton fabric exhibited excellent superamphiphobicity with contact angles of 160.3 and 152° for water and olive oil, respectively. The conductivity and EMI shielding efficiency of the prepared composite cotton fabric reached 629.93 S/cm and 76 dB, respectively. Importantly, the composite cotton fabric maintained a relatively stable EMI shielding efficiency even after cyclic bending and abrasion tests. Moreover, the composite cotton fabric possessed a high limiting oxygen index (LOI) of 45.3% and self-extinguishing properties with the peak heat release rate (PHHR) and total heat release (THR) reduced by 73 and 67%, respectively, than the pure cotton fabric, indicating the outstanding flame retardancy.

Summary Skeletal muscle satellite cells (SCs) are stem cells responsible for muscle development and regeneration. Although CRISPR/Cas9 has been widely used, its application in endogenous SCs remains elusive. Here, we generate mice expressing Cas9 in SCs and achieve robust editing in juvenile SCs at the postnatal stage through AAV9-mediated short guide RNA (sgRNA) delivery. Additionally, we reveal that quiescent SCs are resistant to CRISPR/Cas9-mediated editing. As a proof of concept, we demonstrate efficient editing of master transcription factor (TF) Myod1 locus using the CRISPR/Cas9/AAV9-sgRNA system in juvenile SCs. Application on two key TFs, MYC and BCL6, unveils distinct functions in SC activation and muscle regeneration. Particularly, we reveal that MYC orchestrates SC activation through regulating 3D genome architecture. Its depletion results in strengthening of the topologically associating domain boundaries thus may affect gene expression. Altogether, our study establishes a platform for editing endogenous SCs that can be harnessed to elucidate the functionality of key regulators governing SC activities., Highlights • CRISPR/Cas9/AAV9-sgRNA system yields robust editing in juvenile SCs • Quiescent SCs are resistant to CRISPR/Cas9-mediated in vivo editing • Key TFs play diversified functions during SC early activation • MYC promotes SC activation through impinging on 3D chromatin architecture, In this article, Wang and colleagues generate a CRISPR/Cas9/AAV9-sgRNA in vivo genome editing system to achieve robust editing in juvenile satellite cells (SCs). Application of the system reveals diversified functions of key transcription factors (TFs) during SC activation and uncovers that MYC promotes SC activation through regulating 3D genome architecture. Quiescent SCs, however, are resistant to the in vivo editing.

Prunella vulgaris L. is a perennial herb plant of the Lamiaceae family, and its dried spicas have been widely used as medicine, health-promoting food or tea around the world. P. vulgaris is distributed all over the world, such as Europe, Asia, northwestern Africa and North America, as well as the Huaihe River Basin and the middle and lower Yangtze River Basin in China. In February 2022, a serious disease like gray mold occurred in planting fields of P. vulgaris in Wuhan, Hubei (N30°27′07″, E114°15′49″), causing approximately 20% of plants were diseased in the field. Early symptoms were characterized by small, round gray-brown lesions on the leaves of P. vulgaris. Later, a large number of stems and leaves are wilted or necrotic, associated with wet rot and waterlogged spots and covered with light gray or grayish white flocculent mildew layer. To determine the causal agent of disease, 10 plants with the typical symptoms were collected from fields. The stems and leaves of diseased plants were cut into pieces (2 to 3 mm×5 mm), disinfected with 75% ethanol for 3 minutes, rinsed 3 times with sterile water. Each lesion sample was isolated and purified using separate PDA petri dishes at 25°C, and ultimately all samples yielded morphologically consistent pure strain colonies. From the 10 isolates obtained, XKC-1 was chosen as a representative isolate for further study. XKC-1 colonies showed gray aerial mycelia, which were fast-growing and grew over the whole plate (9 cm) after 4 days. In addition, some black and hard sclerotia (1.88±0.94 mm, n=50) with round or irregular shape developed on the colonies after approximately 10 days of incubation at 25°C (Fig. 2A, B). XKC-1 showed branched conidiophores with enlarged apical cells and numerous conidia (Fig. 2C). Unicellular conidia were colorless or gray, ellipsoid or ovoid, smooth and 7.91-12.38 μm × 10.08-13.82 μm (n=30) in size (Fig. 2D). Based on morphological characteristics, the isolate was initially identified as Botrytis sp. (Ellis 1971). To further identify the species, the genomic DNA of XKC-1 was extracted, and the ITS, LSU and G3PDH genes were amplified with the primers ITS1/ITS4, LROR/LR5 (Zhou et al. 2022) and G3PDH-F/G3PDH-R (Jin et al. 2022), respectively. The results indicated that the ITS (ON090404), LSU (ON090417), and G3PDH (ON169893) sequences were 99.80%, 100% and 99.46% identical to the sequences of Botrytis cinerea Pers. strain (MK370693.1, MN148533.1, MN630267.1), respectively. A phylogenetic tree constructed based on a concatenated sequence (ITS, LSU, G3PDH) using the neighbor-joining method in MEGA7 (Tamura et al. 2013) revealed that XKC-1 grouped with concatenated sequences from three representative B. cinerea isolates in GenBank. Based on the morphological characteristics and molecular identification, the strain XKC-1 was identified as Botrytis cinerea. For pathogenicity tests on detached leaves, 5 mm PDA cakes prepared from XKC-1 were placed on the leaves obtained from healthy P. vulgaris after wounding with a needle (n=10), while PDA medium without mycelia were used as control (25 ± 2°C) (Li et al.2020). Mycelia began to germinate and infect plant tissues at 1 dpi. A large part of the leaves showed water soaked spots covered with mycelia on the surface at 4 dpi. For whole plant inoculations, stem bases of five P. vulgaris seedlings were pierced with sterile needle, and then inoculated with three XKC-1 mycelium PDA cakes. Five plants were inoculated with three PDA cakes without mycelia as a control. After 2-4 days, lesions appeared on the leaves and covered with a gray-white mycelial layer, similar to those observed in the field. However, controls remained symptom free. The pathogen was reisolated from the diseased tissues, the colonies, microscopic characteristics and molecular identification were consistent with those of XKC-1. To our knowledge, this is a first report of B. cinerea causing gray mold on P. vulgaris in Hubei, China. This report would provide resources and reference for controlling of the increased incidence and economic losses of gray mold on P. vulgaris.

IntroductionSmall for gestational age (SGA) infants are at a higher risk of neurodevelopmental delay than infants appropriate for gestational age (AGA). Previous studies have confirmed that gut microbiota in early life influences subsequent neurodevelopment. However, few studies have reported corresponding data in SGA populations.ObjectiveWe aimed to evaluate the characteristics of the gut microbiota of term SGA infants and the associations between the gut microbiota in SGA infants and neurodevelopmental outcomes at 6 months of age.MethodsFecal samples were collected on days 1, 3, 5, and 7 from term SGA and AGA infants born between June 2020 and June 2021 at the Peking University First Hospital. 16S ribosomal deoxyribonucleic acid amplicon sequencing was used to analyze the fecal microbiota. We followed up for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate the neurodevelopmental outcomes among SGA infants.ResultsA total of 162 neonates were enrolled, with 41 SGA infants (25.3%) in the study group and 121 AGA infants (74.7%) in the control group. The gut microbial diversity in the SGA group was lower than that in the AGA group on days 1, 3, 5, and 7. Non-metric multidimensional scaling and analysis of similarities showed significant differences between the two groups. The SGA group had increased relative abundances of Ralstonia (3, 5, and 7 days) and Clostridium (3 and 7 days). The dominant microorganisms of the SGA group were Ralstonia on day 1, Escherichia_Shigella on days 3 and 7, and Clostridia on day 5. We found that the gut microbial diversity of SGA infants with poor communication scores was higher than that of SGA infants with good communication scores on day 3. Fine motor scores were negatively correlated with the relative abundance of Bacteroides_fragilis on day 1. A negative correlation was observed between gross motor scores and relative abundance of Clostridium_saccharobutylicum on day 7. Bacteroidota, Bacteroidia, Bacteroides, and Bacteroides_fragilis were the dominant microorganisms in the good communication score group on day 7. Communication scores were positively correlated with the relative abundance of Bacteroidota, Bacteroides, and Bacteroides_fragilis on day 7.ConclusionThe gut microbial diversity of term SGA infants was significantly lower in the first week of life than that of term AGA infants. Certain pathogenic and conditional pathogenic bacteria, such as Escherichia_Shigella, Ralstonia and Clostridium increased or formed the dominant microbiota in SGA infants. Alpha diversity, Bacteroidota, Bacteroides, Bacteroides_fragilis, and Clostridium_saccharobutylicum found in SGA infants may be associated with neurodevelopmental outcomes at 6 months of age, indicating possible therapeutic targets for clinical intervention.

The authors have requested that this preprint be removed from Research Square.

Skeletal muscle stem cells (also known as satellite cells, SCs) are essential for muscle regeneration and the regenerative activities of SCs are intrinsically governed by gene regulatory mechanisms but the post-transcriptional regulation in SCs remains largely unknown. N(6)-methyladenosine (m6A) modification of RNAs is the most pervasive and highly conserved RNA modification in eukaryotic cells and exerts powerful impact on almost all aspects of mRNA processing which is mainly endowed by its binding with m6A reader proteins. Here in this study, we investigate the previously uncharacterized regulatory roles of YTHDC1, a m6A reader in SCs. Our results demonstrate YTHDC1 is an essential regulator of SC activation and proliferation upon acute injury induced muscle regeneration. The induction of YTHDC1 is indispensable for SC activation and proliferation thus inducible YTHDC1 depletion almost abolishes SC regenerative capacity. Mechanistically, transcriptome-wide profiling using LACE-seq in both SCs and C2C12 myoblasts identifies m6A mediated binding targets of YTHDC1. Next, splicing analysis defines splicing mRNA targets of m6A-YTHDC1. Furthermore, nuclear export analysis also leads to identification of potential mRNA export targets of m6A-YTHDC1 in SCs and C2C12 myoblasts and interestingly some mRNAs can be regulated at both splicing and export levels. Lastly, we map YTHDC1 interacting protein partners in myoblasts and unveil a myriad of factors governing mRNA splicing, nuclear export and transcription, among which hnRNPG appears to be a bona fide interacting partner of YTHDC1. Altogether, our findings uncover YTHDC1 as an essential factor controlling SC regenerative ability through multi-faceted gene regulatory mechanisms in myoblast cells.

Precipitation is an important component of the hydrological cycle and has significant impact on ecological environment and social development, especially in arid areas where water resources are scarce. As a typical arid and semi-arid region, the Mongolian Plateau is ecologically fragile and highly sensitive to climate change. Reliable global precipitation data is urgently needed for the sustainable development over this gauge-deficient region. With high-quality estimates, fine spatiotemporal resolutions, and wide coverage, the state-of-the-art Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG) and European Center for Medium-range Weather Forecasts Reanalysis 5 (ERA5) have great potential for regional climatic, hydrological, and ecological applications. However, how they perform has not been well investigated on the Mongolian Plateau. Therefore, this study evaluated the performance of three IMERG V06 datasets (ER, LR and FR), two ERA5 products (ERA5-HRES and ERA5-Land), and their predecessors (TMPA-3B42 and ERA-Interim) over the region across 2001–2018. The results showed that all products broadly characterized seasonal precipitation cycles and spatial patterns, but only the three reanalysis products, IMERG FR and TMPA-3B42 could capture interannual and decadal variability. When describing daily precipitation, dataset performances ranked ERA5-Land > ERA5-HRES > ERA-Interim > IMERG FR > IMERG LR > IMERG ER > TMPA-3B42. All products showed deficiencies in overestimating weak precipitation and underestimating high-intensity precipitation. Besides, products performed best in agricultural lands and forests along the northern and south-eastern edges, followed by urban areas and grasslands closer to the center, and worst in the sparse vegetation and bare areas of the south-west. Due to a negative effect of topographic complexity, IMERG showed poor detection capabilities in forests. Accordingly, this research currently supports the applicability of reanalysis ERA5 data over the arid, topographically complex Mongolian Plateau, which can inform regional applications with different requirements.

The start of the growing season (SOS) is a vital ecological indicator for climate change and the terrestrial ecosystem. Previous studies have reported that the SOS over the Northern Hemisphere (NH) has experienced remarkable changes in the past few decades. However, because of the different spatial and temporal coverages of existing SOS studies, a coherent and robust account for SOS changes in the NH has been lacking. Using satellite-retrieved vegetation-phenology datasets, ground observations, and several auxiliary datasets, this study evaluated the performance of the latest MODIS vegetation-dynamics dataset (MCD12Q2-C6) and explored the distribution and attribution of the SOS to climate change over the NH for the period 2001–2018. The validation results using the Chinese Ecosystem Research Network (CERN) and Lilac-leafing observations (Lilac) displayed that the MCD12Q2-C6 has a good performance in SOS monitoring over the NH mid-latitudes. Meanwhile, evidence from MCD12Q2-C6 pointed out that the SOS was advanced by 2.08 days on average over the NH during 2001–2018, especially for Europe, China, and Alaska, United States. In addition, detailed-sensitivity analysis showed that the increased surface air temperature (Ts) (−1.21 ± 0.34 days °C−1) and reduced snow-cover fraction (Sc) (0.62 ± 0.29 days%−1) were the key driving factors of the observed SOS changes over the NH during 2001–2018. Compared with Ts and Sc, the role of total precipitation (Pt) was minor in dominating the spring vegetation-phenology changes at the same period. The findings of this study contribute to our understanding of the responses of SOS to the competing changes of Ts, Pt, and Sc over the NH.

Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration and lncRNAs play important roles in regulating SC activities. Here, in this study, we identify PAM (Pax7 Associated Muscle lncRNA) that is induced in activated/proliferating SCs upon injury to promote SC proliferation as myoblast cells. PAM is generated from a myoblast-specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM SE to its inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes upregulation. Altogether, our findings identify PAM as a previously unknown lncRNA that regulates both SC proliferation and aging through its trans gene regulatory activity.

Balance rehabilitation is exceedingly crucial during stroke rehabilitation and is highly related to the stroke patients’ secondary injuries (caused by falling). Stroke patients focus on walking ability rehabilitation during the early stage. Ankle dorsiflexion can activate the brain areas of stroke patients, similar to walking. The combination of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) was a new method, providing more beneficial information. We extracted the event-related desynchronization (ERD), oxygenated hemoglobin (HBO), and Phase Synchronization Index (PSI) features during ankle dorsiflexion from EEG and fNIRS. Moreover, we established a linear regression model to predict Berg Balance Scale (BBS) values and used an eightfold cross validation to test the model. The results showed that ERD, HBO, PSI, and age were critical biomarkers in predicting BBS. ERD and HBO during ankle dorsiflexion and age were promising biomarkers for stroke motor recovery.

This paper investigated three-dimensional breast displacement under different breast support conditions and gait speeds for women with small breasts. The breast coordinates of fifteen female participants with small breasts (sizes ranging from A to C) were recorded during treadmill walking and running tests under two different sports bra conditions and a no bra condition. The results showed that although vertical breast displacement was always the greatest in each condition, mediolateral breast displacement was significantly greater than anteroposterior breast displacement. Mediolateral breast displacement was not effectively reduced in the two sports bra conditions compared to the no bra condition. It is recommended that sports bra designed for women with small breasts should aim to limit mediolateral breast displacement instead of anteroposterior breast displacement, on the premise of controlling vertical breast displacement. The findings also suggest that the effectiveness of sports bras at reducing side-to-side breast movement requires further optimisation.

Due to the extremely high porosity and extremely low density of nano-porous thermal insulation materials, the characteristic size of the pores inside the materials and the characteristic size of the solid skeleton structure are on the nanometer scale, which leads to the obvious nanoscale effect of the heat transfer law inside the aerogel materials. Therefore, the nanoscale heat transfer characteristics inside the aerogel materials and the existing mathematical models for calculating the thermal conductivity of various heat transfer modes at the nanoscale need to be summarized in detail. Moreover, in order to verify the accuracy of the thermal conductivity calculation model of aerogel nano-porous materials, correct experimental data are required to modify the model. Because the medium is involved in radiation heat transfer, the existing test methods have a large error, which brings great difficulties to the design of nano-porous materials. In this paper, the heat transfer mechanism, characterization methods, and test methods of thermal conductivity of nano-porous materials are summarized and discussed. The main contents of this review are as follows. The first part introduces the structural characteristics and specific application environment of aerogel. In the second part, the characteristics of nanoscale heat transfer of aerogel insulation materials are analyzed. In the third part, the characterization methods of thermal conductivity of aerogel insulation materials are summarized. In the fourth part, the test methods of thermal conductivity of aerogel insulation materials are summarized. The fifth part gives a brief conclusion and prospect.

ObjectivesThe purpose of this study was to use easily obtained and directly observable clinical features to establish predictive models to identify patients at increased risk of stroke.Setting and participantsA total of 46 240 valid records were obtained from 8 research centres and 14 communities in Jiangxi province, China, between February and September 2018.Primary and secondary outcome measuresThe area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy were calculated to test the performance of the five models (logistic regression (LR), random forest (RF), decision tree (DT), extreme gradient boosting (XGBoost) and gradient boosting DT). The calibration curve was used to show calibration performance.ResultsThe results indicated that XGBoost (AUC: 0.924, accuracy: 0.873, sensitivity: 0.776, specificity: 0.916) and RF (AUC: 0.924, accuracy: 0.872, sensitivity: 0.778, specificity: 0.913) demonstrated excellent performance in predicting stroke. Physical inactivity, hypertension, meat-based diet and high salt intake were important prediction features of stroke.ConclusionThe five machine learning models all had good predictive and discriminatory performance for stroke. The performance of RF and XGBoost was slightly better than that of LR, which was easier to interpret and less prone to overfitting. This work provides a rapid and accurate tool for stroke risk assessment, which can help to improve the efficiency of stroke screening medical services and the management of high-risk groups.

Simulation experiments and in-vivo experiments were widely employed for investigating sock-skin frictional characteristics. The simulation experiments usually was a type of sliding experiment which described the relative slip between fabric and artificial skin. The in-vivo approaches typically involved subjects adopting a variety of postures and friction between their clothing and the skin was estimated. However, simulation and in-vivo experiments were reported only separately. The connection between the two types of experiments was scarcely reported. To reveal the connection, we synchronously carried out two interrelated experiments, a natural walking experiment and sliding experiment, using the same sock fabric. In the natural walking experiment, the subject wearing socks walked on the force platform. Then the soles of these socks were cut out and were used in the soles-artificial skin sliding experiment. The coefficients of friction in the two types of experiments reflected some correlative frictional characteristics. We found the effect of the walking speed or sliding speed on the friction coefficient was not significant. While, water content increased the friction coefficient in the two experiment. Additionally, the friction in the coronal direction was smaller than that in the sagittal direction during walking. Through our efforts, we hope to bridge the simulation and in-vivo experiments and elucidate the frictional characteristics between the sock and insole.

Flexible thermoelectric materials and devices have gained wide attention due to their capability to stably and directly convert body heat or industrial waste heat into electric energy. Many research and synthetic methods of flexible high-performance p-type thermoelectric materials have made great progress. However, their counterpart flexible n-type organic thermoelectric materials are seldom studied due to the complex synthesis of conductive polymer and poor stability of n-type materials. In this work, bismuth tellurium (Bi2Te3) nanosheets are in situ grown on single-walled carbon nanotubes (SWCNTs) assisted by poly(vinylpyrrolidone) (PVP). A series of flexible SWCNTs@Bi2Te3 composite films on poly(vinylidene fluoride) (PVDF) membranes are obtained by vacuum-assisted filtration. The high electrical conductivity of 253.9 S/cm, and a corresponding power factor (PF) of 57.8 μW/m·K2 is obtained at 386 K for SWCNTs@Bi2Te3-0.8 film. Moreover, high electrical conductivity retention of 90% can be maintained after a 300-cycle bending test and no obvious attenuation can be detected after being stored in an Ar atmosphere for 9 months, which exhibits good flexibility and excellent stability of the SWCNTs@Bi2Te3 composite films. This work shows a convenient method to fabricate n-type and flexible thermoelectric composite film and further promotes the practical application of n-type flexible thermoelectric materials.

New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported. Methods: With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies (CD NAs) through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading of up to 100%. Results: Surprisingly, self-assembled CD NAs show aggregation-induced emission, enabling particle trafficking and drug release in living cells. In preclinical models of human cancer, including a patient-derived melanoma xenograft, CD NAs demonstrated striking therapeutic synergy to produce a durable recession in tumor growth. Impressively, CD NAs alleviated the toxicity of the parent CTX agent and showed negligible immunotoxicity in animals. Conclusions: Overall, this approach does not require any carrier matrices, offering a scalable and cost-effective methodology to create a new generation of nanomedicines for the safe and efficient delivery of drug combinations.

Development of injectable nanoparticles for delivery of active anticancer compounds often requires complicated schemes that involve tedious synthetic protocols and nanoformulations. In particular, clinical translation of synergistic nanoparticles that can facilitate multimodal therapies remains a considerable challenge. Herein, we describe a self-assembling, small-molecule nanosystem with unique properties, including near-infrared (NIR) light-responsive drug activation, size transformability, combinatorial synergy, and substantially reduced toxicity. Ligation of anticancer cabazitaxel (CTX) drugs via a reactive oxygen species-activatable thioketal linkage generates a dimeric TKdC prodrug, and subsequent coassembly with a photosensitizer, chlorin e6 (Ce6), forms colloidal-stable nanoassemblies (termed psTKdC NAs). Upon NIR laser irradiation, psTKdC NAs are transformed into smaller size particles and facilitate production of pharmacologically active CTX. Importantly, reactive oxygen species yielded by coassembled Ce6 can synergize with chemotherapy to achieve potent combinatorial effects. In a preclinical orthotopic model of an aggressive, human melanoma patient-derived xenograft (PDX), we show that administration of psTKdC NAs followed by laser irradiation produced durable tumor regression, with the tumors being completely eradicated in three of six PDXs. Furthermore, low systemic toxicity of this smart, photo-activatable nanotherapy was observed in animals. The new self-deliverable combinatorial system addresses essential requirements for high efficacy, safety, and translational capacity and deserves further investigation.

Drug-carrier compatibility impacts drug delivery efficiency and resulting therapeutic efficacy and tolerability. Although numerous biodegradable carrier materials have been pursued over the past decades, chemical strategies that are sought to tailor therapeutic structures and their carriers together in a concerted effort remain rare yet may be powerful. Based on the principle of improving the structural similarity between these central components, we developed an omega-3 fatty acid-conjugated poly(ethylene glycol) (PEG) nanocarrier host that is capable of supramolecular assembly of a cytotoxic prodrug guest. To demonstrate the proof of concept, we ligated two docosahexaenoic acid (DHA) molecules and one PEG chain via a d-lysine linkage to produce an amphiphilic matrix DHA

With the rapid development of ICT Custom Services (ICT CS) in power industries, the deployed power ICT CS systems mainly rely on the experience of customer service staff for fault type recognition, questioning, and answering, which makes it difficult and inefficient to precisely resolve the problems issued by users. To resolve this problem, in this paper, firstly, a multi-label fault text classification ensemble approach called BR-GBDT is proposed by combining Binary Relevance and Gradient Boosting Decision Tree for assisted fault type diagnosis and improving the accuracy of fault type recognition. Second, for the problem that there is lack of the training set for power ICT multi-label text classification, an automatic approach is presented to construct the training set from the historical fault text data stored in power ICT CS systems. The extensive experiments were made based on the power ICT CS training set and some general-purpose benchmark training datasets. The experiment results show that our approach outperforms the well known ensemble learning based approaches BR+LR and ML-KNN for fault text classification, efficiently handling the multi-label classification of ICT custom service text data for fault type recognition., 23 pages, 1 figure, 5 tables