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The backfill is the safety barrier of the backfilling stopes, and the uniaxial compressive strength (UCS) of the backfill is the key indicator to keep the stability of the backfill. To investigate the actual distribution of the UCS of the backfill in the stopes, a large-scale nickel mine in Northwest China is taken as the research object, and field experiments are carried out to investigate the actual distribution characteristics of the UCS of the backfill at different locations in the underhand drift stopes with different curing times. Further, the machine learning algorithm is used to construct a spatial-temporal distribution prediction model of the backfill UCS with different locations and different curing times as variables, and with the UCS of the backfill as the prediction target, to identify the weak parts and corresponding strengths of the backfill. The results show that the UCS of backfill has the distribution characteristics of increasing and then decreasing in the horizontal direction, and gradually decreasing in the vertical direction. When the curing time of the backfill in the stopes exceeds 80 days, its UCS growth tendency slows down. Compared with the back propagation neural network (BPNN), radial basis function neural network (RBFNN), and general regression neural network (GRNN), the prediction accuracy of extreme learning machine (ELM) is improved by 4.4 %, 3.4 %, and 13.9 %, respectively. Compared with the grey wolf algorithm (GWO) and particle swarm algorithm (PSO), the prediction accuracy of ELM optimized by the sparrow search algorithm (SSA) is improved by 7.2 % and 8.4 %, respectively. The SSA-ELM spatial-temporal distribution prediction model constructed in this study achieves fast and high-precision prediction of backfill UCS, which can provide guidance for stability analysis and quality control of underhand drift stopes.

Solid waste filling is an important development direction for filling mining. This research proposes the preparation of solid waste-based cemented paste backfill (SWCPB) to fill the underground mined area by using waste rock and copper slag as the mixed aggregate and granulated blast furnace slag, steel slag, and desulfurization gypsum as raw materials of solid waste binder to reduce the environmental hazards caused by the industrial solid wastes. Based on the response surface method, experiments are designed to analyze the effect patterns of different factors on the mechanical properties of SWCPB. The formation mechanism of SWCPB mechanical properties is explored based on various microscopic analysis techniques. The mix proportions of SWCPB are designed based on machine learning. The results show that the strength of SWCPB increases and then decreases with the increase of the proportion of copper slag, and gradually increases with the increase of the steel slag dosage and binder-aggregate ratio. The alkaline environment provided by the steel slag causes the glass body in granulated blast furnace slag to depolymerize and react with desulfurization gypsum to produce hydration products, which are the main source of mechanical properties formation in SWCPB. The machine learning model constructed in this research paper has high prediction accuracy for the strength of backfill, which can achieve high-precision optimization of backfill mix proportion. The research results could guide the recycling of solid waste and the efficient use of filling mining technology.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04–6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P

Abstract This paper presents a symmetric all-dielectric two-dimensional grating with high transmittance and high figure of merit based on cylindrical nanoarrays as a liquid sensing structure with small volume and high sensitivity. The device is optimized using the finite element method to calculate the transmissivity under TE/TM polarization. When the incident angle is 4 degrees, the transmissivity of the grating is nearly 1 with a full width at half maximum of 0.016 nm and a sensitivity of 256.2 nm/RIU. The high figure of merit is 16214.936, and the corresponding quality factor can reach 56572.438. The sensor characteristics of the incident angle on the device are analyzed, and the normalized electric field distribution indicates that the change of the incident angle has a significant modulation ability for the resonance energy distribution. The proposed sensor is independent of polarization state, easy to control and integrate, and has broad application prospects in fields such as liquid solution detection, ocean surveys, and position sensing.

Abstract Background Clinical trials have shown that immunotherapy based on Vγ9Vδ2 T cells (Vδ2 T cells) is safe and well-tolerated for various cancers including cervical cancer (CC), but its overall treatment efficacy remains limited. Therefore, exploring the mechanisms underlying the suboptimal efficacy of Vδ2 T cell-based cancer immunotherapy is crucial for enabling its successful clinical translation. Methods Tumor samples from CC patients and CC cell line-derived xenograft (CDX) mice were analyzed using flow cytometry to examine the exhausted phenotype of tumor-infiltrating Vδ2 T cells. The interrelationship between BTN3A1 expression and Vδ2 T cells in CC, along with their correlation with patient prognosis, was analyzed using data from The Cancer Genome Atlas (TCGA) database. CC cell lines with BTN3A1 knockout (KO) and overexpression (OE) were constructed through lentivirus transduction, which were then co-cultured with expanded Vδ2 T cells, followed by detecting the function of Vδ2 T cells using flow cytometry. The pathways and transcription factors (TFs) related to BTN3A1-induced Vδ2 T cells exhaustion and the factors affecting BTN3A1 expression were identified by RNA-seq analysis, which was confirmed by flow cytometry, Western Blot, and gene manipulation. Results Tumor-infiltrating Vδ2 T cells exhibited an exhausted phenotype in both CC patients and CDX mice. BTN3A1 expressed in CC is highly enhancing exhaustion markers, while reducing the secretion of effector molecules in Vδ2 T cells. Blocking TCR or knocking down nuclear receptor subfamily 4 group A (NR4A) 2/3 can reverse BTN3A1-induced exhaustion in Vδ2 T cells. On the other hand, IFN-γ secreted by Vδ2 T cells promoted the expression of BTN3A1 and PD-L1. Conclusions Through binding γδ TCRs, BTN3A1 expressed on tumor cells, which is induced by IFN-γ, can promote Vδ2 T cells to upregulate the expression of TFs NR4A2/3, thereby affecting their activation and expression of exhaustion-related molecules in the tumor microenvironment (TME). Therefore, targeting BTN3A1 might overcome the immunosuppressive effect of the TME on Vδ2 T cells in CC.

Summary: Human primary cardiomyocytes are a valuable in vitro model for studying human heart physiology and disease. Here, we present a protocol for the dissociation of adult human primary cardiomyocytes using a methylcellulose-supplemented digestion solution. We describe steps for sample collection, tissue pre-processing, and cell dissociation. We then detail procedures for calcium reintroduction and viability assessment. This protocol can significantly improve the efficiency of cardiomyocyte isolation and subsequent cell function, making them an even more reliable model for cardiac research.For complete details on the use and execution of this protocol, please refer to Shi et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract With the widespread application of composite insulators in transmission lines, exploring the accumulation mechanism of pollution particles on composite insulator surfaces is of importance to ensure the safe and steady operation of the power system. Addressing the current theoretical shortcomings, this study categorises the accumulation process of particles on the insulator surface into three stages, namely ‘spatial motion’, ‘surface collision’, and ‘surface motion’. The motion and rotation velocities in a multi‐physics field are calculated in the spatial motion stage. In the surface collision stage, a parameter called ‘neck height’ is introduced to determine the optimum mechanics theory, and the normal deposition criterion is established. For the surface motion stage, the sliding displacement and rolling displacement on the surface are calculated based on the rotation speed of the particles. A dynamic pollution accumulation model of the composite insulator is established based on the normal deposition criterion and tangential displacement. Finally, numerical simulations are performed by using the finite element method. Simulation results show that the proposed model agrees with the actual insulator pollution accumulation, and the deposition model is still applicable for various types of composite insulators operating in different applied voltages. The deposition probability of particles increases with the increasing particle size. In the surface motion stage, particle displacement increases with particle size and wind velocity.

Introduction: Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. Objectives: We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. Methods: We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. Results: We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. Conclusion: We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

Abstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.

Abstract Background Osteoporosis (OP) is a progressive metabolic disorder that is difficult to cure clinically. The molecular mechanisms of OP urgently need to be further examined. This study was designed to explore the potential function of circ_0027885 during osteogenic differentiation, as well as the systematic interactions among circ_0027885, miR-203-3p and runt-related transcription factor 2 (RUNX2). Methods Relative levels of circ_0027885, miR-203-3p and RUNX2 were analyzed with RT-qPCR and western blotting. Alizarin red staining was performed to detect the mineralization ability under the control of circ_0027885 and miR-203-3p. Dual-luciferase reporter gene assay was conducted to examine the combination among circ_0027885, miR-203-3p and RUNX2. Results Our research demonstrated that circ_0027885 was significantly increased during hBMSCs differentiation. Overexpression of circ_0027885 notably facilitated osteogenic differentiation and upregulated RUNX2 expression, while knockdown of circ_0027885 reversed the above results. Through prediction on bioinformatics analysis, miR-203-3p was the target binding circ_0027885, and RUNX2 was the potential target of miR-203-3p. Subsequently, these changes induced by the overexpression of circ_0027885 were reversed upon addition of miR-203-3p mimic. Conclusions Circ_0027885 could sponge miR-203-3p to regulate RUNX2 expression and alleviate osteoporosis progression.

Obtaining high-quality adult human primary cardiomyocytes (hPCM) have been technically challenging due to isolation-induced biochemical and mechanical stress. Building upon a previous tissue slicing-assisted digestion method, we introduced polymers into the digestion solution to reduce mechanical damage to cells. We found that low-viscosity methylcellulose (MC) significantly improved hPCM viability and yield. Mechanistically, it protected cells from membrane damage, which led to decreased apoptosis and mitochondrial reactive oxygen species production. MC also improved the electrophysiological properties of hPCMs by maintaining the density of sodium channels. The effects on cell viability and cell yield effects were not recapitulated by MC of larger viscosities, other cellulose derivatives, nor shear protectants polyethylene glycol and polyvinyl alcohol. Finally, MC also enhanced the isolation efficiency and the culture quality of hPCMs from diseased ventricular myocardium, expanding its potential applications. Our findings showed that the isolation quality of hPCMs can be further improved through the addition of a polymer, rendering hPCMs a more reliable cellular model for cardiac research.