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In a group of deep coal seams, mining of upper multilayers generates cyclic loading–unloading stresses in bottom layers, improving their permeability and enhancing coalbed methane gas drainage. In this study, the respective repeated mining stress path was introduced into the seepage test. A high-resolution 3D X-ray microscopy imaging system was used for computed tomography scanning of coal samples. The crack characteristics and stress–permeability relationships were analyzed based on the experimental results. It was found that the permeability increased approximately by 5.8 times after the loading–unloading cyclic tests. The fracture volume and rate grew obviously, and the complexity degree of the fracture network increased. The permeability evolution during the test was closely related to stress–strain state of the coal sample with variable response characteristics of axial deviatoric stress, confining pressure, and axial pressure. The realization of different numbers of loading–unloading cycles in the tests revealed similar fracturing effects of the initial and later cycles, whereas the largest fracturing effect was obtained within the effective stress range from 4 to 11 MPa. The mechanical deformation was found to play an important role in the stress–permeability relationship. The crack closure and elastic deformation at low stress-state caused the permeability loss, while crack growth and plastic deformation at high-stress state increased the permeability. The plastic strain significantly grew with the number of loading–unloading cycles, but the fracturing effect of different numbers of cycles in the critical fissure point was nearly the same. The results obtained are considered instrumental in studying the pressure relief and extraction of coalbed methane during upper protective layer mining in coal seam groups.

Coalbed methane is a lucrative energy source, but its development relies heavily on the fracturing of coal seam and underground extraction during mining. This study of mining stress paths, pore pressure, and permeability of a coal body was aimed to overcome the constraints of low coal permeability under the stress applied to a coal seam group. Variation in the applied stress changes the effective stress in coal and its permeability (which also depends on pore pressure). The effects of different mining intensities, repetitive cyclic loading and unloading, and pore pressure on gas permeability in a coal mine are revealed and discussed. The permeability evolution curve can be described by quadratic polynomial equations and split into three (decreasing, stable, and increasing) stages. When the stress environment with low axial deviatoric stress changes to that with high axial deviatoric stress and when the stability stage becomes longer, the goodness of quadratic polynomial data fitting is reduced. Cyclic loading and unloading with different axial stress paths have different effects on coal permeability. Increased axial and confining pressures decrease the permeability and pore pressure sensitivity of permeability. Because the obtained permeability-pore pressure curves contain a stable stage, this sensitivity is more pronounce in the low and high pore pressure stages.

Dabie bandavirus (DBV) is an emerging Bandavirus that causes multiorgan failure with a high fatality rate in humans. While many viruses can manipulate the actin cytoskeleton to facilitate viral growth, the regulation pattern of the actin cytoskeleton and the molecular mechanisms involved in DBV entry into the host cells remain unclear. In this study, we demonstrate that expression of nonstructural protein (NSs) or infection with DBV induces actin rearrangement, which presents a point-like distribution, and this destruction is dependent on inclusion bodies (IBs). Further experiments showed that NSs inhibits viral adsorption by destroying the filopodium structure. In addition, NSs also compromised the viral entry by inhibiting clathrin aggregation on the cell surface and capturing clathrin into IBs. Furthermore, NSs induced clathrin light chain B (CLTB) degradation through the K48-linked ubiquitin proteasome pathway, which could negatively regulate clathrin-mediated endocytosis, inhibiting the viral entry. Finally, we confirmed that this NSs-induced antiviral mechanism is broadly applicable to other viruses, such as enterovirus 71 (EV71) and influenza virus, A/PR8/34 (PR8), which use the same clathrin-mediated endocytosis to enter host cells. In conclusion, our study provides new insights into the role of NSs in inhibiting endocytosis and a novel strategy for treating DBV infections. IMPORTANCE Dabie bandavirus (DBV), a member of the Phenuiviridae family, is a newly emerging tick-borne pathogen that causes multifunctional organ failure and even death in humans. The actin cytoskeleton is involved in various crucial cellular processes and plays an important role in viral life activities. However, the relationship between DBV infection and the actin cytoskeleton has not been described in detail. Here, we show for the first time the interaction between NSs and actin to induce actin rearrangement, which inhibits the viral adsorption and entry. We also identify a key mechanism underlying NSs-induced entry inhibition in which NSs prevents clathrin aggregation on the cell surface by hijacking clathrin into the inclusion body and induces CLTB degradation through the K48-linked ubiquitination modification. This paper is the first to reveal the antiviral mechanism of NSs and provides a theoretical basis for the search for new antiviral targets.

Gliomas refer to a group of complicated human brain tumors with a low 5-year survival rate and limited therapeutic options. Extremely low-frequency pulsed electromagnetic field (ELF-PEMF) is a specific magnetic field featuring almost no side effects. However, the application of ELF-PEMF in the treatment of gliomas is rare. This review summarizes five significant underlying mechanisms including calcium ions, autophagy, apoptosis, angiogenesis, and reactive oxygen species, and applications of ELF-PEMF in glioma treatment from a clinical practice perspective. In addition, the prospects of ELF-PEMF in combination with conventional therapy for the treatment of gliomas are reviewed. This review benefits any specialists, especially oncologists, interested in this new therapy because it can help treat patients with gliomas properly.

Influenza A virus (IAV) poses a significant threat to human health, which calls for the development of efficient detection methods. The present study constructed a fluorescence resonance energy transfer (FRET) system based on novel fluorescent probes and graphene oxide (GO) for detecting H5N1 IAV hemagglutinin (HA). Here, we synthesized small (sub-20 nm) sandwich-structured upconversion nanoparticles (UCNPs) (SWUCNPs for short) with a high energy transfer efficiency, which allows for controlling the emitter in a thin shell. The π-π stacking interaction between the aptamer and GO shortens the distance between the fluorescent probe and the receptor, thereby realizing fluorescence resonance energy transfer (FRET). When HA is present, the aptamer enables changes in their conformations and move away from GO surface. Fluorescence signals display a linear relationship between HA quantitation in the range of 0.1-15 ng mL-1 and a limit of detection (LOD) of 60.9 pg mL-1. The aptasensor was also applicable in human serum samples with a linear range from 0.2 to 12 ng mL-1 and a limit of detection of 114.7 pg mL-1. This strategy suggested the promising prospect of the aptasensor in clinical applications because of the excellent sensing performance and sensitivity. This strategy may be promising for vitro diagnostics and provides new insights into the functioning of the SWUCNPs system.

Dendritic cells (DCs) are vital hubs for exciting systemic adaptive immune responses. But the uppermost antigen presenting cells are in a state of severe suppression in breast carcinoma for making tumor cells more resistant and viable. In order to reverse this immunosuppressive state in the tumor microenvironment, here we showed that non-pathogenic Sendai virus (SeV) is employed to execute multi-channel recruitment and excitation of DCs. Simultaneously, the signal of “don't eat me” on the surface of tumor cells is blocked with a CD47 blocker to greatly enhance the phagocytosis and antigen presentation of macrophages to the tumor cells. With the excitation of these two cells by SeV and CD47 blocker nanocomposites, breast carcinoma antigens are presented to the lymph nodes in large numbers to mature T lymphocytes for specifically killing tumor cells. Our findings indicate that the nanohybrids can successfully excite DCs and macrophages in vitro and in vivo, and then systemically arouse cytotoxic T lymphocytes and helper T lymphocytes, and further motivate the formation of humoral immunity and immune memory. Therefore, the oncolytic nanocomposite strategy combining non-genetically modified viruses and immune checkpoint inhibitors might serve as the next generation of personalized anti-tumor immunotherapy agents, representing an alternative way to suppress tumor metastasis and recurrence.

Microbial-based cancer therapy is nowadays considered as an interesting approach, especially with viruses which are attracting more attention owing to their simple structure and nanoscale. However, because of the need for cumbersome genetic modification and poor biosafety, its application is seriously limited. Here, nonpathogenic natural Sendai viruses (SEVs) are used as an alternative immune agonist after being mineralized by calcium ions. Both in vitro and in vivo studies indicated that virus-inorganic hybrids can effectively excite antigen-presenting cells (APCs). Then, the tumor antigens were released in large amounts by photothermal damage. Meanwhile, these released antigens were presented to lymph nodes to mature antitumor T lymphocytes via the peritumoral APCs previously recruited by the SEV. Our results demonstrated that even after administration at one point, the nanohybrids could still effectively stimulate systemic antitumor immune response to suppress the potential cancer metastatic spread. The bio-inorganic hybrid nongenetically modified virus-inorganic nanocomposites might serve as an alternative strategy for synergistic immune therapy.

Two α,ω-diene monomers containing a carbonate structure derived from eugenol and 2-methoxy-4-vinylphenol were successfully synthesized in high yields of 94% and 78%, respectively. With these dienes in hand, a series of poly(thioether carbonates) and unsaturated aromatic–aliphatic polycarbonates with moderate molecular weights (Mn) ranging from 17 100 to 24 400 g mol−1 and tunable thermo-properties were prepared via a thiol–ene click reaction and step growth acyclic-diene-metathesis, respectively.

The factors affecting permeability change under repeated mining of coal seams are important study aspects that need to be explored. This study combined various stress variation characteristics of protective seam mining and simplified the stress path of repeated mining in protective seam mines. Based on the results from the bespoke gas flow and displacement testing apparatus, seepage tests for simulated repetitive mining were carried out. The results simulated the actual behavior very well. With any drastic increase in the mining influence, the axial deviation stress in the stress path increased, and the greater the difference in coal permeability during the unloading and stress recovery stage, the more substantial the increase in permeability. The change in coal permeability was significantly influenced by the severity of simulated repeated mining cycles. When the mining stress exceeded a critical value, the permeability of the coal sample increased with the increase in the number of loading and unloading cycles, but the reverse was true when the mining stress was lower than the critical value. The effective sensitivity of seepage to the applied stress decreased with an increase in the number of stress cycles. With a decrease in the deviation stress, that is, with lower severity of mining influence, the effective sensitivity of coal seepage to stress gradually decreased.

Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-00970-w.

The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through “respiratory droplets”. Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to prevent virus infection from respiratory tract. The nanovaccine that mimic virosome is composed of poly(I:C) mimicking viral genetic material as immune adjuvant, biomimetic pulmonary surfactant (bio-PS) liposomes as capsid structure of virus and the receptor binding domains (RBDs) of SARS-CoV-2 is used as a “spike”, so as to completely simulate the structure of the coronavirus. The nanovaccine can be administered by inhaling to imitate the process of SARS-CoV-2 infection through the respiratory tract. Our results demonstrated that the inhalable nanovaccine with bionic virus-like structure has a stronger mucosal protective effect than routine muscle and subcutaneous inoculation. In particular, high titer of secretory immunoglobulin A (sIgA) was detected in respiratory secretions, which effectively neutralize the virus and prevent it from entering the body through the respiratory tract. Through imitating the structure and route of infection, this inhalable nanovaccine strategy might inspire a new approach to the precaution of respiratory viruses.

In order to study the seepage law of broken coal seams affected by multiple mining operations, a cyclic loading and unloading seepage experiment was carried out. For this purpose, the seepage law of broken samples with different coal and rock ratios was analyzed. The results of our study demonstrated that the permeability of the broken samples showed a decreasing trend. After a loading and unloading cycle, the permeability was significantly reduced. The impact of the loading stage on the broken sample was higher than that of the unloading phase. When the proportion of coal particles in the mixed samples of broken coal and rock was 50%, the irreversible permeability loss rate and permeability loss rate of the samples showed the highest values. The irreversible permeability loss rate and permeability loss rate of the broken rock mass were greater than those displayed by the broken coal mass. The stress sensitivity coefficient curves of the 5 types of broken coal and rock masses presented the same changes. The stress sensitivity coefficient curve and the effective stress displayed an exponential relationship.

As humans and climate change continue to alter the landscape, novel disease risk scenarios have emerged. Sever fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease first discovered in rural areas of central China in 2009, is caused by a novel bunyavirus (SFTSV). The potential for SFTS to spread to other countries in combination with its high fatality rate, possible human-to-human transmission, and extensive prevalence among residents and domesticated animals in endemic regions make the disease a severe threat to public health. Because of the lack of preventive vaccines or useful antiviral drugs, diagnosis of SFTS is the key to prevention and control of the SFTSV infection. The development of serological detection methods will greatly improve our understanding of SFTSV ecology and host tropism. We describe a highly sensitive protein detection method based on gold nanoparticles (AuNPs) and enzyme-linked immunosorbent assay (ELISA)&mdash, AuNP-based ELISA. The optical sensitivity enhancement of this method is due to the high loading efficiency of AuNPs to McAb. This enhances the concentration of the HRP enzyme in each immune sandwich structure. The detection limit of this method to the nucleocapsid protein (NP) of SFTSV was 0.9 pg mL&minus, 1 with good specificity and reproducibility. The sensitivity of AuNP-based ELISA was higher than that of traditional ELISA and was comparable to real-time quantitative polymerase chain reaction (qRT-PCR). The probes are stable for 120 days at 4 &deg, C. This can be applied to diagnosis and hopefully can be developed into a commercial ELISA kit. The ultrasensitive detection of SFTSV will increase our understanding of the distribution and spread of SFTSV, thus helping to monitor the changes in tick-borne pathogen SFTSV risk in the environment.

BACKGROUND: Medulloblastoma (MB) is a common central nervous system tumor in children with extensive heterogeneity and different prognoses. This study aimed to classify the Ki-67 index in MB with radiomic characteristics based on multi-parametric magnetic resonance imaging to guide treatment and assess the prognosis of patients. METHODS: Three sequences of T1W, CE-T1W, and T2W were used as test data. Two experienced radiologists manually segmented the tumors according to T2W images from 90 patients. The patients were divided into training and test sets at a ratio of 7:3, and 833 dimensional image features were extracted for each patient. Five models were trained using the feature set selected in three ways. Finally, the area under the curve (AUC) and accuracy (ACC) were used on the test set to evaluate the performance of the different models. RESULTS: A random forest (RF) model combining three sequence features achieved the best performance (ACC: 0.771, 95% CI: 0.727 to 0.816; AUC: 0.697, 95% CI: 0.614 to 0.78). The voting model that combined a RF and a support vector machine (SVM) had higher performance than the other models (ACC: 0.796, 95% CI: 0.76 to 0.833; AUC: 0.689, 95% CI: 0.615 to 0.763). The best prediction model that used only one sequence feature was voting in the T2W sequence (ACC: 0.736, 95% CI: 0.705 to 0.766; AUC: 0.636, 95% CI: 0.585 to 0.688). The ensemble model was better than the single training model, and a multi-sequence combination was better than a single sequence prediction. The multiple feature selection methods were better than a combination of the two methods. CONCLUSIONS: A model obtained by machine learning could help doctors predict the Ki-67 values of patients more efficiently to make targeted judgments for subsequent treatments.

Hypertriglyceridemia is a risk factor for a series of diseases, such as cardiovascular disease (CVD), diabetes and nonalcoholic fatty liver disease (NAFLD). Angiopoietin-like proteins (ANGPTLs) family, especially ANGPTL3, ANGPTL4 and ANGPTL8, which regulate lipoprotein lipase (LPL) activity, play pivotal roles in triglyceride (TG) metabolism and related diseases/complications. There are many transcriptional and post-transcriptional factors that participate in physiological and pathological regulation of ANGPTLs to affect triglyceride metabolism. This review is intended to focus on the similarity and difference in the expression, structural features, regulation profile of the three ANGPTLs and inhibitory models for LPL. Description of the regulatory factors of ANGPTLs and the properties in regulating the lipid metabolism involved in the underlying mechanisms in pathological effects on diseases will provide potential therapeutic approaches for the treatment of dyslipidemia related diseases.

The coal permeability is known to be influenced by the pore pressure and effective stress in coal mines. In this study, the characteristics of the bituminous coal permeability response to the pore pressure and effective shear stress in the Xutuan coal mine in Huaibei Coalfield in China were investigated under different stress conditions. For this purpose, gas seepage tests with various stress levels were conducted via the original gas flow and displacement testing apparatus using bituminous coal samples from the Xutuan coal mine. The pore pressure effect on the permeability under different stress conditions was assessed by varying the pore pressure in coal samples and simulating different in situ stresses. The axial and radial pressures were controlled to study the response of coal permeability to the effective shear stress. The experimental results revealed that with an increase in pore pressure, the permeability of coal in different stress environments firstly drops and then rises. The permeability increased gradually with the effective shear stress, which trend became more pronounced when the effective shear stress exceeded zero. In case of the axial pressure exceeding the radial one, the cross shear slip was observed, for which the permeability of coal samples increased with the effective shear stress. In the opposite case, the separated shear slip was observed, with the reverse trend.

Objective: To optimize and verify the cellulase extraction of polyphenols from honeysuckle and provide a reference for enzymatic extracting polyphenols from honeysuckle. Materials and Methods: The uniform design was used According to Fick's first law and kinetic model, fitting analysis of the dynamic process of enzymatic extracting polyphenols was conducted. Results: The optimum enzymatic extraction parameters for polyphenols from honeysuckle are found to be 80% (v/v) of alcohol, 35:1 (mL/g) of liquid-solid ratio, 80°C of extraction temperature, 8.5 of pH, 6.0 mg of enzyme levels, and 130 min of extraction time. Under the optimal conditions, the extraction rate of polyphenols was 3.03%. The kinetic experiments indicated kinetic equation had a good linear relationship with t even under the conditions of different levels of enzyme and temperature, which means fitting curve tallies well with the experimental values. Conclusion: The results of quantification showed that the results provide a reference for enzymatic extracting polyphenols from honeysuckle. SUMMARY Lonicerae flos (Lonicera japonica Thunb.) is a material of traditional Chinese medicine and healthy drinks, of which active compounds mainly is polyphenols. At present, plant polyphenols are the hotspots centents of food, cosmetic and medicine, because it has strong bioactivity. Several traditional methods are available for the extraction of plant polyphenols including impregnation, solvent extraction, ultrasonic extraction, hot-water extraction, alkaline dilute alcohol or alkaline water extraction, microwave extraction and Supercritical CO2 extraction. But now, an increasing number of research on using cellulase to extract active ingredients from plants. Enzymatic method is widely used for enzyme have excellent properties of high reaction efficiency and specificity, moderate reaction conditions, shorter extraction time and easier to control, less damage to the active ingredient. At present, the enzymatic extraction of polyphenols from honeysuckle and dynamic had not been reported. In this study, using cellulase to extract polyphenols from honeysuckle is first applied. Moreover, uniform design was used to optimize process and kinetic model of extraction was established to analyze the characteristics of enzymatic extraction, in order to improve the yield of polyphenols from honeysuckle and make maximum use of Lonicerae flos, which provide references for industrial production.